Revision as of 13:41, 20 July 2021

Human Practices

Fig. 1 Our team collected insights from a variety of players in the field

RDT Need

Question: Which challenge is iGEM Leiden 2020 going to take on?

Input

Our team started the iGEM experience with a very open attitude, hoping to address an important societal issue. Our team decided to work in the field of infectious diseases. As we dug into literature and talked to experts, we aimed to identify a need in this vast field.

World Health Organization

As part of their effort in emergency preparedness and response, the WHO keeps a record of the outbreaks that occur yearly. The latest outbreaks include Yellow fever, influenza A virus, Ebola virus, Plague, MERS-CoV, Measles, Dengue, as well as SARS-CoV-2. Certain diseases, such as Ebola, are recurrent in tropical and Subsaharan regions¹. Yellow Fever ² is endemic in Africa and Central and South America, whereas the endemic regions affected by Dengue ³ are even larger. These outbreaks of diseases need to be addressed with funds but also medical developments. This is all the more important in regions with fewer resources.

McNerney, R. (2015). Diagnostics for developing countries. Diagnostics, 5(2), 200-209⁴.

Lower-income countries have a higher incidence and prevalence of communicable diseases, because of a lack of correct diagnosis and follow-up treatment for the patients, due to geographical or financial reasons. As a consequence, they often face difficulties preventing the further transmission of these diseases.

Dr Assica Permata, M.D. currently working on TB in a research environment

Dr Permata told us about the situation in Indonesia, where patients in large cities usually could get tested. However, in smaller cities, where the laboratory facilities are not optimal, the samples have to be sent to larger facilities and patients may have to wait days to weeks for the results.

Peeling & Mabey, 2010⁵.

In the developing world, there is a need for point of care tests, as they can help speed up the diagnosis of bacterial, parasitic, and viral diseases. Additionally, the quality of the tests has to be improved. Systems for quality control and improving training in the use of the kit can help improve the quality of the tests.

Robin van Houdt, microbiologist at the Dutch Association for Medical Microbiology and the UMC Amsterdam

Robin van Houdt told us that RDTs are also very useful in developed, high-income countries where hospitals dispose of sophisticated laboratories. RDTs could be used to tests patients upon entry in the hospital, for instance, identifying the patients that should be treated in isolation. This could help save a lot of time and money, and is better for the patient’s wellbeing. RDTs could also be used to quickly test an entire ward if an infection does occur. This could then prevent spread to other parts of the hospital.

Huram Konjen, Chief executive officer of Dianox

Mr. Konjen told us that the need to improve diagnostics lies in the need to address and reduce the elevated costs associated with testing. These costs are mainly lab costs such as equipment and the staff.

Integration

Infectious diseases are the most important enemy of the health of humankind, translated as seasonal colds, urinary infections, but also haemorrhagic fevers, respiratory affections or septic shocks.

When our team first sat down around a table to discuss the purpose of our project, a very obvious, threatening situation was cooking on the other side of the planet. The COVID-19 pandemic seeped through each of our conversations and interfered with our habits and way of life. It reminded us of the damage and chaos that a few nano/micrometers of biology can cause in entire populations.

Particularly in the middle and low resource areas, the increased emergence of these outbreaks and the lack of sufficient medical resources yield an important death toll, even for preventable and treatable diseases⁶.

Our team therefore decided to take on the challenge of developing an economical and accessible rapid diagnostic test (RDT) for infectious diseases.

Rapid diagnostic tests can be used with minimal equipment and are suitable for emergency situations, where low resources are available, but not only. The speed of the tests is also particularly appreciated as delays in diagnosis can result in the poorer prognosis of the patients. For some neglected or less prevalent infectious diseases, there is a true, urgent need for more specific, accurate, and accessible diagnostic tools. Diagnosis of other, more prevalent diseases such as Malaria, require more qualitative tests, in a market flooded with low-cost tests.

Science

Question: Developing a rapid diagnostic test for infectious diseases: where do we start?

Input

The first step to develop a rapid diagnostic test is to determine the technical, scientific means at our disposal and to compare it to existing methods, to identify a starting point. To do so, our team turned to our predecessors in the iGEM community, in the hope to learn from their experience and launch our ambitious quest.

Niek Savelkoul, iGEM 2017 Wageningen Mantis & Founder of Scope Biosciences

Niek shared his experience in the iGEM 2017 Mantis project, in which they attempted to develop a multiplex rapid test for infectious diseases. However, they did not manage to get a functional kit. He said that using a cell receptor sensor presented too many limitations, such as a delay due to the transcription and the fact that it contained living material. He suggested that a cell-free system would be preferred.

Prof. dr. Janneke van de Wijgert, professor in epidemiology UMC Utrecht & Liverpool

According to professor Janneke van de Wijgert, in general, a molecular-based diagnostic kit has an advantage over antigen/antibody-based or chemical biomarker-based kits when considering reliability. However, reliability depends on the type and complexity of the disease.

Dr Peter Bredenbeek, assistant professor in Virology LUMC

With Dr. Bredenbeek we discussed which scientific considerations were important. He stated that to be successful, our kit should be at least as sensitive as PCR, which is able to detect up to 4-5 copies/mL of sampled blood. He also encouraged us to include a positive and negative control in each of the kits.

Thomas Caltagirone, CEO of Alpagen LLP

We discussed with Dr. Caltagirone his publication of 2018, on a technique that is able to cause a color change in the reaction with the help of a DNAzyme, called the GQ-EXPAR system⁷. He told us that the amplification of the target in the tube would help to reduce false positives and increase the intensity of the colorimetric output.

Dr Armand Paauw, Scientist at TNO Defence, Security and Safety, & Dr Hans van Leeuwen, Senior Scientist at TNO

LAMP is a factor 5 to 10 less sensitive than qPCR. This is problematic for LAMP because qPCR will always be picked over LAMP in a lab environment. This means that if your kit is to be used in a lab, then it has to compete with qPCR and be at least as good. If your kit is meant for a setting outside of the lab (point-of-care), it is acceptable to lose some sensitivity. The point-of-care nature makes up for the loss in sensitivity.

iGEM EPFL 2019 ViTest

Thereafter, we reached out to the iGEM 2019 team from EPFL, that worked on developing a sensor for wine diseases as they used the RPA technique for amplification. They told us that RPA is highly specific and sensitive, but that as a result contaminations can interfere with the results. They suggested using the TwistDX kit for RPA.

Integration

At the start of our project, we reached out to the 2017 iGEM Mantis project, to understand the challenges they faced and to identify our starting point. One of their challenges, integrating living cells with an antibody library in a test kit, was not feasible. Our team, therefore, decided to opt for a cell-free system, comprised of enzymes and rather stable nucleic acids. This also enabled to bypass the challenge that antigen tests may face and allows to directly identify the pathogen using molecular techniques.

Literature also suggested that the RPA method is more sensitive than PCR (the golden standard, and reference technique for many infectious diseases) in a controlled environment⁸. Additionally, RPA is a good option as it does not require a power source and would enable equipment-free use.

Finally, technical considerations pushed forwards by many parties was the need for a qualitative, easily-detectable and foolproof output, which would leave no room for interpretation. Our team therefore got inspired by the common ELISA tests. By using a peroxidase DNAzyme with hemin, positive samples would undergo an immediate and very clear color change. Our team has also thought about the integration of the controls in the kit as seen on our Hardware page

Application

Question: How can we identify a niche in the vast and complex field of infectious diseases?

Input

The preliminary steps in our project indicated that there is a need for more and better diagnostics. Nevertheless, the need may differ depending on the disease and the sociogeographical situation of the patient. In the quest for an application, our team reached out to patients and experts in the field to understand where the specific medical, but also societal needs and challenges lie, for each of the diseases.

Dr Peter Bredenbeek, assistant professor in Virology LUMC

The first pathogen we naturally thought of was the pathogen responsible for the current pandemic, the coronavirus, as no molecular test had yet been approved. However, Dr. Bredenbeek strongly discouraged us from choosing SARS-CoV-2 as an application. We would be competing with very large companies that possess extensive resources and large networks. These companies are racing for financial gain and scientific novelty in a highly pressured environment. Aligned with iGEM's advice and expectations, we decided not to linger on this topic and instead, look into other applications.

René Paulussen, managing director Mondial Diagnostics

Our team set out to further research other pathogens, of which Vibrio cholerae. However, Mr. Paulussen discouraged us from developing a test kit for this disease. When an outbreak occurs in a community, only the first patients are diagnosed. Other patients with the same symptoms are treated for cholera without further testing. This is due to the epidemic nature of cholera. The cholera market is, therefore, an extremely low margin market for high development costs, which would not be viable for a project like Rapidemic.

Dr Lieselotte Hardy, Doctor at Institute of Tropical Medicine Antwerp, Belgium

Dr. Hardy focuses on infectious diseases and their diagnosis and has worked on projects in Sub Saharan Africa and Asia. She mentioned that the diagnosis of bacterial bloodstream infections is still insufficient and that a rapid diagnostic test (RDT) for these infections would be fruitful. However, she also mentioned that in the case of bacterial sepsis, the concentration of the bacterial agent can be very low. This input was confirmed by one of Hardy's colleagues, who is a medical doctor. While there is a need for better diagnosis of this affection, even in hospital settings, diagnosis of sepsis would require multiplex testing of various pathogens, which might not be accommodated by our kit.

Dr Heleen Koudijs, Tropical doctor

Dr. Koudijs also discussed TB as a potential disease our technology could be applied to. However, she mentioned that Genexpert has good control over the market. A drawback Genexpert has is that the kit is quite expensive.

Mosquito-born diseases

Dr Heleen Koudijs, Tropical doctor

Dr. Koudijs proposed several mosquito-borne diseases, one of these is Malaria. According to Dr. Koudijs, the market for RDT for malaria is quite saturated. There are a lot of cheap RDT's available for malaria. The reason why they are so cheap is because the companies are funded by organizations such as the WHO, Gates Foundation, and other NGO's. As a consequence, malaria might not be the best disease to focus on.

Dengue and Malaria patients

We questioned patients diagnosed with Dengue (3) and Malaria (3) in Honduras, Argentina, Zambia, Congo, Costa Rica, and Indonesia about their diagnostic procedures. Some of the patients stated that they experienced difficulties in reaching a doctor to get tested, demonstrating that access to healthcare is not always easy. The patients experienced a very slow and inaccurate diagnosic procedure of the dengue virus and stated that it needs to be improved. Malaria patients also had to undergo repeated testing, even when tested in centers with experienced doctors. The patients expressed that they would prefer a quicker diagnostic procedure that would require less blood sampling.

Hélène van Oorschot, Student in medicine

With Mrs. van Oorschot we discussed malaria and dengue as potential applications. She discouraged mosquito-borne diseases in general because if there is an epidemic, quarantine would not help. Apart from this, with malaria as an application, our kit would also compete with the medicine itself. This is because malaria medicine is cheap and readily available. For example, if the patient has the symptoms of malaria, but microscopy does not diagnose malaria, the patient is still given malaria medicine. In addition, testing for dengue is questionable as there is no cure available. Patients can therefore only be treated for their symptoms, rather than the source of disease, such as preventing dehydration.

Disease X and Epidemic preparedness

Professor Pim Martens, Maastricht Sustainability Institute, director of the International Centre for Integrated assessment and Sustainable development (ICIS), School of Business and Economics, founder of AnimalWise and member of House of Animals, member of Dutch Health Council

Professor Martens worked on predicting the spread of Malaria and the associated risks. He told us that Malaria is still a very important disease to focus on in diagnostics as it is multifactorial and complex. Deforestation, increasing travel behavior, climate change, intensive farming and the increase in population density are increasing the emergence and the spread of novel pathogens, likely from zoonotic origin. Therefore, when we asked him which pathogen he would like to detect he responded:

"I would go for the one we don't know yet"

Dr Armand Paauw, Scientist at TNO Defence, Security and Safety, & Dr Hans van Leeuwen, Senior Scientist at TNO

The two scientists at TNO told us that influenza would be a good application, since this is a rapidly mutating virus and has potential to cause an epidemic/pandemic. Besides this, the high mutation rate is something that can be addressed well by the modular nature of the kit. However, one should then be able to prove that the test can be quickly used for various diseases and, by extension, adapted to novel diseases.

Willem Mees van der Bijl, Director IDE Netherlands at IDE Group

Mr. Van der Bijl mentored us on the kit development. Rather than trying to implement one product that can detect any pathogen, he advised focusing the development effort on a specific diagnostic application at first and extending the application later to the diagnosis of other diseases.

Integration

A DNA/RNA sensor could be adapted to any human infectious disease. Soon after reaching out to the experts in the field of infectious diseases, our team realized that identifying a niche in the field of diagnostics of infectious diseases would require us to balance the science of our kit with many external factors. These, for instance, include the medical need for an RDT, the patient's preferences, the identification of a gap in the diagnostic market, but also the feasibility of the implementation, due to regulation and logistics.

Our team was driven by a desire to address a societal and humanitarian need for better diagnosis. The input of the patients was triggering, as it made us very invested in improving the diagnostic procedures. Pinpointing an application pushed us to acknowledge and work with the qualities and the limitations of the science of our kit, to inherently match its application. While we allowed ourselves to aspire to ambitious goals, we made it a prime point in this project to identify a niche and an application that would be realistic and viable.

At first, by focussing on specific diseases such as Lyme disease, Cholera, bloodstream or urinary infections, and TB, our team aimed to respond to a specific diagnostic need. However, we then soon realized that when doing so, we were positioning ourselves in direct competition with the sensitivity, cost, quality, and accuracy of the current methods of diagnosis of these diseases, without being certain that our kit would be able to truly answer an unmet need.

While conducting more integrated and holistic research, our team looked into current diagnostic methods for mosquito-borne diseases such as Dengue, Yellow Fever, and Malaria. Patients and doctors confirmed that there are struggles with the detection of these diseases, particularly prevalent in tropical zones. Today, these diseases affect hundreds of millions of people each year. It is predicted that these diseases will likely spread towards the North as the effects of climate change will force the vectors of these diseases upwards, affecting even more people. However, these diseases do not progress through direct human-to-human transmission. This means that quarantine measures based on test results will not have any influence on the spread of the disease. A rapid diagnostic test could replace the "golden standard" diagnosis of these diseases in certain low-income areas. However, as many rapid tests for Malaria have already been developed, it may be unconstructive to compete with diagnostic tools already on the market. As a consequence, we were not completely conviced that this application would be the optimal niche for our rapid and modular application.

We then took a step back an reflected on the scientific content of the tests we had imagined. The use of primers in a molecular test would entail that they can be replaced for any pathogen, emphasizing the kit's potential for modularity. Therefore, we presented a novel idea to the experts, which was received with great enthusiasm: tackling novel outbreaks with epidemic potential at their source to prevent their spread. However, they warned that it is difficult to convince stakeholders in the field of a modular idea, as it might raise skepticism on the feasability of such an ambitious endeavour. Therefore, our team looked into diseases that have great pandemic potential, which rapidly led us to respiratory RNA viruses, such as the group of Orthomyxoviridae and Coronaviridae. These pathogens are known to cause disease and mutate quickly, making them very likely to cause a next great outbreak. Our kit could be used to rapidly address the need for tests, even in the most remote and low resource areas.

Timeline

Exploring the needs in rapid diagnostics → Mosquito-borne diseases → Disease X → Respiratory-borne RNA viruses

Users and User-friendliness

Questions: Who is going to use our kit? Where is our kit going to be used?

Input

From an accessibility viewpoint, self RDTs are optimal as they do not require medical assistance and can be distributed and sold in pharmacies, directly to the population. We interviewed patients from different areas of the world, business players and doctors that have worked in areas with limited lab or hospital access to understand whether self-testing is the most appropriate option.

Dr Sophie van Baalen, Researcher team medical technology for Rathenau institute

Even though we aimed our kit to be used by patients, we did not only discuss patients as possible end-user with Dr van Baalen. According to her, the benefit of having the patient perform the test themselves is that there is no need for professionals to perform them. However, the benefit of having professionals handling the kit is that you have better quality control and immediate follow-up care. Moreover, it enables the collection of epidemiologic data from the tests. In the setting of outbreaks of infectious diseases, this crucial information would enable real-time monitoring of the spread.

Patients: Malaria, TB, Dengue and SARS-CoV-2

We first questioned patients (13) from around the world diagnosed with Malaria, Dengue and Tuberculosis to compare the diagnostic need and settings as well as to understand their preferences.

When asked whether they would feel comfortable performing a finger prick test or a nasal swab themselves, the vast majority responded that they would not feel comfortable doing so, and prefer to be assisted. We also asked whether they would trust a test performed by a doctor more or less than a self-RDT. Out of the nine people that answered this question, six said that they would trust a self-RDT less than a test conducted by a doctor.

We then also asked COVID-19 patients about their diagnostic experience. We found that if a patient does not experience symptoms that are unique or characteristic of a disease, or if the probability of getting the disease is not (very) high, patients do not think of purchasing a test for this specific disease unless they had been advised by their doctor.

Additionally, we questioned the risk of self-RDTs for the patients' health. Indeed, if a patient performs a self-RDT and tests positive, the patient would not be in a setting where it can immediately be provided with treatment if necessary. If the patient tests negative, the patient cannot test further for other diseases, nor have access to additional medical care, such as IV fluids or analgesia.

Finally, a patient reminded us that in certain countries, social security is a well-structured system that enables reimbursement to the patients. If a patient in these regions self-tests, but then also wishes to visit a doctor for a second opinion, self RDTs might be an additional procedure, thus an additional cost. A solution would be to sell RDTs solely under prescription.

René Paulussen, managing director Mondial Diagnostics

As it is challenging to bring a testkit to the market, Mr Paulussen discouraged us from making a home self-test right away. Indeed, companies first have to build up and a reputation and credibility. He, therefore, suggested starting by developing the kit for laboratories with limited infrastructure, where the tests can be conducted by minimally trained staff. This way, the quality can be safeguarded and, in turn, improves the credibility and reputation. Later on, the kit can be made more accessible to less/non trained individuals.

Dr Heleen Koudijs, Tropical doctor

While working in Ethiopia, Dr Koudijs found that a large share of the population is analphabetic. Therefore, she does not trust the patient to perform the test themselves. She thus recommended developing the kit with health centers or health professionals working in posts in rural villages as end-users. They are probably the best way to reach rural villages as they are greatly respected by the locals.

Eric de Coster, Medical coördinator in the General Infectious Disease Control and Travel Advice

Mr de Coster told us about what happens when a patient tests positive for a disease in health centers (GGD) in the Netherlands. The GGD tests the patients, but also gathers the data (results) and sends the anonymized files to the National Institute for Public Health and Environment (RIVM). Collecting data is crucial as it can help to manage the spread of diseases and subsequently determine decisionmaking on a governmental level.

How can we then ensure that our kit is userfriendly?

Identifying the end-users of the tests is crucial as it is inherently related to the design of the kit and eventually the reliability of the outcome. Therefore, we sought to know which considerations are important in order to build a physical kit and to render it userfriendly and the result unequivocal.

Dr Heleen Koudijs, Tropical doctor

Dr. Koudijs has worked with RDT's during her time in Ethiopia. However, according to her, the corona test kit used by doctors in Ethiopia lacks a clear description and has a very confusing design. This resulted in unnecessary errors and false results. Therefore, Dr. Koudijs highly recommended ensuring that a clear instruction manual (pamphlet) is present as well as a simple, clear kit design.

John Tonkinson, Chief Business Development Officer DCN Dx

Mr. Tonkinson told us to make use of engineering to complete the biological limitations that the kit might present. He strongly emphasized anticipating the slightest errors that one could make. The results should also not leave any room for interpretation, as this is a source of errors. Clear color-coding to show the outcome is a good example to prevent interpretation.

René Paulussen, managing director Mondial Diagnostics

Mr Paulussen also had some remarks about the design of our kit. He proposed to use the KISS strategy (Keep It Simple, Stupid). Therefore, the explanations of the kit should be given in pictograms, such that they can be understood by everyone, regardless of their education level. The different reagents (such as the buffer and the sample) that should be added together should be color-coded as well.

Professor dr Aldrik Velders, Nanobiotechnology at Wageningen University & Dr Vittorio Saggiomo, Organic Chemistry

The two chemists working on developing microfluidic devices told us that it is important to keep the handling of the device to a minimum and to limit the possibility of contaminations to ensure a reliable outcome. Thus, ideally, the kit should be as passive as possible and happen in a single reaction tube.

Integration

Certain limitations of self-testing, such as the increased chance of false results due to human error and the absence of appropriate data gathering, indicate that patients should probably not be entrusted with the manipulation of the kits themselves.

The input gathered indicates that patients as well as doctors and developers think it is best to consider trained staff as users of the kits. Patients are not eager to perform medical procedures themselves, even minor ones. The patients overall would not prefer performing a kit from the comfort of their homes as they would like to get proper follow-up care in the case of a severe disease.

Out of concern for equality, we do not want to compromise the accessibility nor the quality, and instead find the right balance between both. Therefore, our team thinks that the tests could be used by hospital staff, but also NGOs or trained technicians that could be mobilized in the field or in crowded areas such as airports and in cities. The kits could also be performed by staff in schools, essential businesses, or elderly homes. Performing tests by trained staff also facilitates data collection for epidemiology, so important in outbreaks of infectious diseases. Trained staff will also be more inclined to properly dispose of the kit, which contains material from a potentially infected patient (see Disposal).

Furthermore, the experts reminded us of certain considerations that, when applied, can help safeguard the quality of the test. The test should be made as intuitive, easy and robust as possible. Indeed, our team attempted to minimize the amount of handling by conducting the reactions with buffers that could accommodate the different components and conduct reactions with the least amount of material possible (fewer reaction tubes, centrifugation steps, using generic buffers or adapt the pH).

To avoid interpretation, experts confirmed that a colorimetric output is a good option. The test would be given along with a color indicator, as well as an integrated positive and negative control in the test, with the aim to minimize human error.

More about the design of the kit can be found on the Hardware page.

Timeline

Exploring the needs in rapid diagnostics → Mosquito-borne diseases → Disease X → Respiratory-borne RNA viruses

Affordability

Question: How can we ensure that the cost of a test does not compromise the accessibility to all?

Input

Proper healthcare is a basic need, however, it has to be paid for to be sustained. We attempted to understand the cost of exitsting RDTs, and how we can make ours affordable for all.

Niek Savelkoul, iGEM 2017 Wageningen Mantis & Founder of Scope Biosciences

Niek told us that behind projects to improve diagnostics lie a strong philanthropic desire. As many RDTs are developed for low resource areas, the tests cannot be too expensive as they would not be used in the regions in need.

Prof. dr. Janneke van de Wijgert, professor in epidemiology UMC Utrecht & Liverpool

Professor van de Wijgert said that most RDTs are not widely available. In resource-poor countries, almost all tests are considered too expensive.

John Tonkinson, Chief Business Development Officer DCN Dx

Mr. Tonkinson told us that typically during pandemics, tests are funded or subsidized by foundations working with local governments (such as the Gates foundation). He told us that they set the cost depending on the budget and that the test kits should then be produced for that price. Therefore, the tests have to be economical and the prices have to be set at the beginning of the development process. He also told us that producing in very large amounts, as is done for Malaria RDTs, enables us to drastically reduce the price per kit.

Erik van Vught, Goffin Molecular Technologies

Mr van Vught said that a kit should not cost more than 10€, as determined by the market, or perhaps 12€ if the test is very unique. This price should include the costs of distibution and logistics. However, doing distribution ourselves would jeopardize the value creation out of our sales. Therefore, it is recommended to outsource distribution.

Dr Dam, Medical doctor

Dr. Dam told us that in The Netherlands tests for this pandemic were paid by the government. For other infectious diseases, the tests are paid by health insurance companies.

Dr Heleen Koudijs, Tropical doctor

In order to get the cost of the kit low, Dr. Koudijs told us it is important to follow the guidelines of UNESCO, UNICEF, WHO and other NGO's. For many lower-income countries, these organizations fund the purchase of diagnostic tests. In other countries, like Ethiopia, the government pays for medical devices.

Dr Sophie van Baalen, Researcher team medical technology for Rathenau institute

Dr. Van Baalen also suggested thinking about strategies to ensure equal distribution during a pandemic. For example by adopting a model in which high-income countries would pay a higher price for test-kits than lower-income countries.

Integration

In a pandemic where the entire world is affected, everyone should have access to diagnosis. However, everything has a price, and a business cannot continue to provide products without income. Diagnostics should be sold at a very low price as usually they are government-funded, but sometimes also by foundations and NGOs. Therefore, businesses have to work with an immuable, limited budget. An economical test would allow governments to be able to test more, and repeatedly.

An advantage of molecular diagnostics is that they tend to be rather economical. Our team tried to approximate the cost of a single test reaction performed in the lab. The cost of a single detection (as determined by the purchase cost of the reagents, sequences, buffers, and enzymes) was around $1.45, without the hardware (as determined on our Proof of Concept page). If the kit is mass-produced, this price can be lowered even further.

Our team felt that the cost of a kit should not limit the access to diagnostic devices. We therefore plan to implement a self-sustaining hybrid economic system to make our kits affordable. In this hybrid model, the price of the tests would depend on the income of the countries. High income countries, would then pay a "premium" price that would co-fund the purchase of tests by NGOs or governments in lower income countries.

Logistics & Regulation

Question: How can kits reach our kits reach the target population? How can they be distributed accordingly?

Input

It is probably rather easy for an inhabitant of high-income countries to get tested for a particular disease. However, for certain regions, it can be a true challenge to reach a target population⁹. Therefore, our team has asked experts which challenge should be overcome to reach the populations that can benefit most from our development. This entails research on regulations but also some logistical aspects of distribution.

Regulations

Qserve

Qserve is a consultant company that helps diagnostic companies to get a CE label from the notified bodies. There are two notified bodies in the Netherlands, Dekra inc. and BSI. A CE label is proof that a product conforms to the European regulation and is therefore essential when bringing a product to the European market. The EU regulation our kit needs to abide by, in order to obtain the CE marking, is the In Vitro Diagnostic Regulation 2017/746. The notified bodies test our kit independently to ensure that our kit abides by the regulation.

Erik van Vught, Goffin Molecular Technologies

When trying to receive approval to sell our kit overseas, Mr van Vught suggested to first market the product in our own country, the Netherlands, as it is one of the leading countries in (molecular) diagnostics, therefore also the most critical market. If it works in the Netherlands, we would be more comfortable selling it in other countries.

René Paulussen, managing director Mondial Diagnostics

Outsourcing or licensing a part of our business to large companies is the optimal for bringing our kit on a foreign market as they have a great sales and distribution network and often have contacts with regulatory bodies or government members. The latter is important as good relations with the local government facilitates the approval and implementation of the devices.

Ward Heij, Monitor Deloitte

Ward Heij told us that there is a difference between public and private markets. Procurement for public healthcare is often centralized either on a national or regional level. Sometimes, smaller consortia of hospitals procure together. It is rare that individual hospitals procure for themselves. Additionally, procurement is often done through tendering. It is also important to remember that due to price competition, better quality is not necessarily sought after. Often, the cheapest product that matches all certifications is sold.

Guus Eskens, Retired researcher and CEO of CARE Nederland

Guus shared with us some of his extensive experience with CARE Netherlands, Cordaid, IDA Foundation, and years of living in Africa. He provided us with insight into the state of the market for diagnostics and therapeutics in Africa. In certain countries, the major players in the medical field are international NGOs, often financed by large funds or wealthier countries. These NGOs work with funding programs (or missions), where they address a single crisis situation. The equipment and drugs are purchased depending on the goods that have been certified, tested, and approved by large bodies such as the FDA and the WHO. The equipment is then imported into the area in need. In a crisis situation, the complicated and delocalized logistics, may cause an inevitable administrative delay in bringing a novel product from the lab to the field. Therefore, to get into this market, the kits have to be approved by the larger bodies. The idea of modularity is interesting, but it will never be approved by these bodies if the tests are modular. As a consequence, the immediate, "rapid response" to epidemics is not fully achievable.

Distribution/Logistics

René Paulussen, managing director Mondial Diagnostics

According to Mr. Paulussen, distribution is always a challenge. However, the difficulty lies in getting our kit approved in the countries where we want to sell. Once we get our approval first, then the distributors will come.

Dr Otto Kroesen, researcher of cross-cultural entrepreneurship for development

Dr. Kroesen also proposed that (a part of) the production could be done in Africa. He gave South Africa as an example to do packaging in. However, it is definitely important to take into account what the benefits are of moving production to Africa.

René Paulussen, managing director Mondial Diagnostics

Distribution in Sub-Saharan Africa happens on trucks driving through the desert. The temperature inside these trucks can exceed 55°C. Therefore, it is essential that the kits are robust and can withstand these extreme temperatures.

Dr Heleen Koudijs, Tropical doctor

Dr Koudijs told us that in Ethiopia RDTs are distributed in distribution centers (mostly from UNICEF) on scooters on walking paths to the remote villages.

John Tonkinson, DCN Dx

Mr. Tonkinson suggested making a kit with the least plastic possible, small and compact, which would be easier for transport.

Guus Eskens, Retired researcher and CEO CARE Nederland

Mr. Eskens told us that the conditions for logistics and distribution in certain remote places, like on the African continent, can vary greatly. These variations can complicate the distribution in certain regions. The availability and reliability of electricity can compromise the cold transport chain and the very long distances between regions yield high distribution costs. The temperature in containers left in harbors without a cooling system can reach 60-70°C. Their unreliability can be a problem to safeguard the quality of the tests.

Integration

Regulations

Understanding the regulations that govern the market of diagnostic devices globally is important. Experts helped us understand what it takes to bring a kit to a market where the standards are extremely high, versus a market where low(er) cost applications are often the norm.

Indeed, in high-income countries, the governments make up stocks of basic medical necessities. Therefore, the products have to be tested and approved by the notified bodies (such as the CE marking). In contrast, in lower income countries, large NGOs fund these medical supplies and are funded by foundations. They purchase these based on recommendations from bodies like the WHO. Therefore, kits first have to be tested and approved and gain a reputation on the market. However, there is a risk that modular kits might not reach the target users as quickly as initially intended due to inevitable administrative delay. Yet the nature of our kit (pre-produced generic part) could help in reducing this delay in an epidemic setting.

From a business perspective, it is complicated to market and commercialize a modular kit that cannot be tested immediately. Therefore, our team has become aware that we have to start small and gradually build up the product to its final, modular application. By focussing on the group of respiratory-borne RNA viruses, our kit could already be applied and tested for specific diseases like influenza. If we prove that the kits respond to the requirements for specific diseases (sensitivity, accuracy, speed), it can increase the credibility of our modular application, build up a reputation and accelerate their approval and implementation in a crisis situation.

Distribution/Logistics

In lower-income countries, including many countries on the African continent, transport and logistics are often difficult for complex, bulky, fragile, refrigerated medical devices. Therefore, robustness and temperature insensitivity are the qualities sought after in a kit. Additionally, the distribution costs in more isolated regions can be very elevated. As a consequence, the regions where these kits are highly needed are eventually poorly covered in the required medical supplies.

The majority of the reagents in the Rapidemic test kits can be freeze-dried, which can respond to the need for better conservation and subsequent long-term storage and distribution of the products. We predict that this could also render the reagents more resistant to high temperatures¹⁰. Additionally, as we are aiming to design the embedding of the test reagents in a simple, robust device, this will likely require less specialized distribution systems.

The exact hardware of the kits has not yet been detemined. However, given that very little volume of the reagents is necessary, the kits could be made in a very compact format. Our team has even considered doing a paper-based test. This will also facilitiate the distribution of the tests.

Disposal

Question: How can we make ensure that our kit is disposed of in a safely manner?

Input

As mentioned in "Users and user friendliness", the best way to make sure that the kit is properly disposed of is by entrusting trained professionals with the use of the kit. In the Netherlands, the hospitals are responsible for managing their own waste. How can we ensure that the used kits present no environmental or health risk whatsoever, in the Netherlands and abroad? Which waste category would used kits qualify as?

Dr Armand Paauw, Scientist at TNO Defence, Security and Safety, & Dr Hans van Leeuwen, Senior Scientist at TNO

According to the two scientists, our kit should be considered as contaminated hospital waste and should be disposed of accordingly. They also said that in order to inactivate the pathogens, the samples should be lysed entirely, which would render the pathogens harmless. This can be achieved with a lysis buffer, for instance. However, they suggested testing whether the pathogens are effectively neutralized and that a lysisbuffer is sufficient to do so. Alternatively, they told us that the samples could be inactivated by steaming them for 10 minutes at 80°C before disposal.

Waste transporting company

Bram de Graaf, Project Manager hazardous waste NNRD

The NNRD is a waste transporting company responsible for the waste collection and transport for the areas Drachten and Groningen. All the waste transporting companies in the Netherlands follow the regulations from the ADR. The driver has to have an ADR diploma and the truck has to be ADR certified as well. After the waste is collected from the hospitals, the waste is dropped brought to the depot until there is enough waste to be transported to the waste disposal company Zavin in Dordrecht.

Waste disposal company

Ron Roffel, Operational director Zavin

According to Mr. Roffel, the hospital staff in the Netherlands is rather considerate of waste separation and disposal infrastructure. However, he said that Dutch general practitioners sometimes fail to separate their medical waste correctly, yet this is improving. According to Mr. Roffel, if the waste disposal of point-of-care kits is left to the general public (patients), proper separation of the medical waste is practically unachievable.

We also learned from this visit that the majority of medical waste worldwide is improperly disposed of, even in Europe. In a best-case scenario, all the medical waste is incinerated in the open air. In worse conditions, the kit may end up in an open landfill or in nature. In the latter case, the kit should be hermetically sealed off and non-hazardous, to ensure it does not present a health threat to the population.

To read more about our visit to Zavin: Click here!

The future of waste diposal

Gerard Vincent, CEO Red Bag Solutions Europe

Red bag solutions is an alternative option for medical waste disposal in the Netherlands. Instead of incineration, they use water sterilization. The benefits of their technique are mainly environmental. They can reuse up to 95% of all their materials. This tech also saves up almost 100% of nitrogen and 75% of CO2 from medical waste.

Waste disposal in Africa and Asia

Dr Heleen Koudijs, Tropical doctor

According to Dr. Koudijs, the waste in Ethiopia is thrown on top of a pile until the pile is big enough to be incinerated out in the open. However, the situation in hospitals is better. Hazardous waste in hospitals in Ethiopia is well separated. It is very unclear how the waste is separated and processed in countries like Zambia and Tanzania.

Dr Assica Permata, M.D. currently working on TB in a research environment

Dr. Permata shared with us how infectious waste is handled in Indonesia. One of the anecdotes that stuck with us is the fact that some doctors expose contaminated material to sunlight for sterilization. The remaining waste is disposed of in bags and likely burned.

Integration

Through contact with the diagnostic companies, we have rapidly understood that RDT developers do not integrate the end-of-life considerations, such as environmental or (health) safety, into the developmental stages of the products. We also realized that developing a medical product for low-resource countries with inadequate infrastructure can present certain risks, that should be taken into account in the design process. Therefore, we contacted professionals in the field to understand how our team could consider and integrate these considerations into our project, even at a very early stage.

After our kit has been used, it will be classified as hospital waste and should therefore be treated as such. In the Netherlands, the quality of the disposal systems in place is not perfect, yet the country is among the best in the world. Just a few countries further, the quality of the waste treatment is drastically worse or even non-existent¹¹. Often, the disposed medical waste is mixed with regular house waste and landfilled, or incinerated without post-treatment of the fumes.

When kits are properly incinerated, there is less environmental value in making our test kits from degradable material (with harmless contents), such as biodegradable plastics. One way to further decrease the impact of the kits would be to use recycled content to reduce the unnecessary incineration of virgin material. However, opting for recycled materials sometimes also entails decreased polymer quality and therefore reduced robustness. This may affect the choice of material since it is important that the quality and robustness of the kits are maintained. Additionally, if the kits are incinerated, all potentially infectious material is killed.

Instead, if the hospital waste is placed in a landfill to which the population has access, the content of the kits could present a risk. Therefore, the potentially infectious material should be lysed. The use of biodegradable materials could decrease the environmental impact of the kits in these circumstances.

Ethics

Question: What social considerations do we need to take into account when doing business in different areas of the world?

Input

Doing business in Africa is certainly not the same as doing business in Europe. Topics like culture, social taboos, trust and extreme poverty all play a significant role in determining if our product is going to be a success or a failure.

Dr Heleen Koudijs, Tropical doctor

A significant portion of the Ethiopian population lives in extreme poverty. This means many people in Ethiopia earn less than one euro per day. Therefore, taking a day off to test has severe consequences for the families. Testing in Ethiopia is regulated and performed by the Ethiopian government. The patients are tested and then put into isolation (quarantine) until the results are in. If the result of the test is positive then they are isolated two more weeks, if not then they are free to go. This has severe financial consequences for the families involved. Another cultural consideration is that Ethiopians will probably not wait long to get the test result. According to Dr Koudijs, keeping people in hospitals was, therefore, quite the issue. To combat this, it is recommended to have a kit that has a test result within two hours. Lastly, having a disease (like HIV, for instance) in countries like Kenia is a big social taboo. Privacy is therefore crucial and should not be neglected.

Dr Otto Kroesen, researcher in cross-cultural entrepreneurship for development

According to Dr. Kroesen, there is very little trust in shop owners. Even physicians are not always trusted. If the kits are given to health workers for free then there is a good chance that kits will go missing. However, for any transaction, it is important to have the trust of the locals. It is also important to have kits handled by trustworthy people. Trust can be earned through schools and churches. However, it does take a lot of time to gain trust.

Integration

Social considerations should not be forgotten when trying to enter the African market. Gaining trust is of vital importance. The best strategy regarding the quickest entry into the market is licensing our product to a company with a good reputation and which is trusted by the local population. The social considerations regarding the feeling of being looked down upon and the social taboo related to a disease (like HIV) are struggles that are mainly affecting the physicians. Therefore, these issues cannot be solved by an RDT since these issues are cultural. The fact that people are not willing to wait is problematic. Fortunately, this issue can be (partially) solved by having shorter (less than 2 hours) reaction times.

A day at Zavin

Overview

Sometimes as scientists, we tend to forget the world outside the lab. Innovations succeed inside the laboratory doesn’t mean it can be applied to the real world. An important aspect we need to consider is how our technology can be applied in society. Thus, human practice became one of the major pillars of our project, to test our project against the challenges in the real world. We believe that only through working with both professionals and consumers can we ensure that our product is beneficial to all. Our approach to human practices involved working with both professionals and the general public to understand their opinions and tailoring our project to meeting their demands. Through our interactions, we get to explore different aspects of the project that we would otherwise ignore, including intellectual property, sustainability, laws, and regulations.

The world is changing daily, and with it, talents, skills, and experience needs to be a part of that growth cycle too. With the growing controversy on GMOs and live therapeutics, we realized our iGEM project is at the heart of this discussion. The research and results on live therapeutics are few and far between, with it only being brought to attention these past few years. There are still so many challenges and obstacles live therapeutics have to face before it is widely accepted as a treatment method. We realized that no matter how much research we do, we ended with more questions unanswered than answered. Can we make it out onto the market, and survive in the harsh and competitive environment? How do we ensure our product’s viability in the market? What is the current stance of the world when it comes to living therapeutics? To ensure we are able to finalize the different aspects of our products, we decided to turn to different aspects of society, engaging with doctors, nurses, researchers, professionals involved in the legal and business side of drug and device development, patients, students, and the general public.

Thus, we visited places like dialysis centers, laboratories, biotech companies and also IPO (Intellectual Property Office) to learn from experts in their fields, and understand more on how to improve our project.

Expert Visits

Healthcare Expert Visits

Dialysis Center Visit

Dry Labs Visits

Enterprise Visits

Winston Medical Supply Co.

GeneFerm Biotechnology Co., LTD.

GenMont Biotech Inc.

NARLabs (National Applied Research Laboratories)

Synbio Tech Inc.

Government Association

TFDA (Taiwan Food and Drugs Administrations)

IPO (Intellectual Property Office)

Survey

OMG Survey

Expert visits

Before we are able to get started on developing our idea into a product, we need to make sure that our idea is as close to perfect as possible, and that means tons of research and experiments. But, the real problem with many ideas, and perhaps the reason why many fail to become a success, is a lack of expertise. No matter how much time and effort we put into research, there will always be an expert who knows the topic or even industry much better than we do. So, to help further verify and improve our ideas, we visited several experts in different fields.

Dr. Te-Hui Kuo 4/15

Attending Physician, Division of Nephrology, National Cheng Kung University Hospital

We met with Dr. Te-Hui Kuo to gain knowledge about Chronic Kidney Disease. He provided us with invaluable insight into the connection between p-Cresol and Chronic Kidney Disease. We met with him during the early stages of the project, and he advised us to keep expanding on the idea of using blood measurement for uremic toxins. He also warned us that the public and even doctors don’t pay much attention to uremic toxins, which encouraged us to design activities to spread awareness, which you can find in our public engagement.

Dr. Junne-Ming Sung 6/25

Director and Attending Physician, Division of Nephrology, National Cheng Kung University Hospital

We met with Dr. Junne-Ming Sung to talk more about the viability of our device in the market. He guided us to think about the future of our device, highlighting several questions we had never thought of. His valuable insight allowed us to begin shifting the trajectory of our device to have a more functional role in the market. Instead of just being able to prove our biotherapeutic works, our device now has the potential to become a cornerstone in the diagnosis of Chronic Kidney Disease.

Ms. Li-Hui Huang 7/11

Nurse, Chia Yi Chang Gung Memorial Hospital Dialysis Center

In an activity hosted by Taiwan Chronic Kidney Disease Foundation, we had the opportunity to meet Ms. Li-Hui Huang. As someone who interacts with CKD patients on a daily basis, she was able to give us more insight on a CKD patient’s needs and wants. She talked us through the treatments that CKD patients undergo, mentioning that dialysis was often used as a prevention method for CKD patients, and they need to undergo dialysis three times a week. While uremic toxins and uric protein checks are important for CKD patients, they do not do routine checks on it - and even if they do, they only do creatinine checks once a month.

Ms. Yu-Chen Kuo 8/29

Chronic Kidney Disease Nurse Specialist, National Cheng Kung University Hospital

As a CKD Nurse Specialist, she periodically give lectures on how to handle CKD patients and background knowledge on the disease, and thus, knows the disease very well. She taught us quite a lot about the disease, especially about the treatments. While there is no current treatment that can fully cure the patients, she does admit that the patients will sometimes take Chinese Herbal medicine or even go for acupuncture to give themselves a peace of mind. When we mentioned our project, she mentioned a current drug currently insured by National Health Insurance (NHI) that could be our market competitor. In order to make it in the Taiwanese market, she advised us to consider our drug being insured by NHI, as the government has policies regarding CKD in Taiwan, and thus insured most CKD treatments.

Feng Dian United Dialysis Center

We visited Tainan Dialysis Center to learn more about patients undergoing dialysis treatments. and to find out whether CreSense can be a good fit if placed in dialysis centers. We also met with Dr. Shun-Jie Hsu and Dr. Kuan Wen Chen who gave us plenty of advice for our device. They agreed that there was currently a gap in the market for a p-Cresol reader, or any other kind of uremic toxin readers. However, they warned us that especially in small dialysis centers like this, the cost of the device and treatments need to be considered.

We also talked about the mindset of patients undergoing dialysis. Not many know the connection of p-Cresol or other uremic toxins with CKD, and only 10% of patients know about gut bacteria. We talked to one CKD patient undergoing dialysis, and he mentioned that his CKD had developed from diabetes - which is considered quite common. Despite not knowing about uremic toxins, he does know that CKD can lead to cardiovascular disease.

Professor Yi-Je Juang

Professor, Department of Chemical Engineering, National Cheng Kung University

While we were testing PDMS chip, we encountered a problem. When we injected whole blood into the blood separation chamber, the blood would flow into the reaction chamber instantly, causing impureness of the plasma. We hope to stop this from happening so we went to Professor Juang to ask suggestions toward our microfluidic wafer. He suggested us to apply a passive valve on the channel between the whole blood chamber and the reaction chamber. The passive valve can stop the flow of the blood without incurring any additional operation, which improved the purity of the plasma we gained significantly. Furthermore, He told us to retry on the PDMS spinning test (the PDMS would burst during centrifuge at that time) since theoretically, PDMS layers should strongly adhere together and it should be inseparable. Also, he suggested us to use double-sided tape in the combination of the acrylic disc, which is proved to be effective. By having a fruitful meeting with him, we restored our faith in PDMS and improved our project by applying passive valve and double-sided tape in the microfluidic disc.

Professor Chia-Yuan Chen

Associate Professor, Department of Mechanical Engineering, National Cheng Kung University

We proposed our idea about creating a device using microfluidic chips in mind, however we were not exactly sure how to apply the chip into our device. Professor Chen was very helpful as he discussed with us about the type of microfluidic chip that can be used in our device, how the chip will integrate with other parts of the device, and whether our chip is reusable or not. He told us to try using PDMS chip because it’s affordable and it has the same performance as acrylic chip. From this discussion, we then decided to use PDMS-based microfluidic chip. Professor Chen then provided us with resources in his lab and taught us the required PDMS chip fabrication skills. By his help, we successfully made a few version of PDMS microfluidic chips.

Professor Ruey-Jen Yang

Chair Professor, Department of Engineering Science, National Cheng Kung University

We consulted Professor Yang when we kept failing on creating the PDMS microfluidic chip as the runner joint made of PDMS will rupture during centrifugation process. Although the third version of the wafer is reinforced at the joint, we still hope to find an alternative before the third version of the wafer comes out. Since Professor Yang has done low-cost paper-based chip development and micro-flow channel design, we hoped to get help and his advice in this regard.

After asking and briefly describing what we wanted to do, he suggested us to find his student who was doing a PDMS-related study. He told us that the bond between PDMS and PDMS is weaker than the bond between PDMS and glass and acrylic. It is recommended that we try to use PDMS and acrylic binding to test whether the strength could have a higher performance. Other problems also include the parameters of the oxygen plasma during binding that will also affect the binding effect (the pressure and time of the binding). Professor Yang then suggested that we make the whole acrylic disc into a microfluidic disc, which will save some space and fixed processes and introduced Ph.D. Weng to us. By his suggestion, we went to Ph.D. Weng and tested acrylic materials for bonding in our third version of the device.

Ph.D. Chen-Hsun Weng

Chief of Industry-Academic Collaboration in Medical Device Innovation Center, Tainan

We went to Ph.D. Weng to learn about paper-based microfluidic chip and how to use acrylic engraving machine and we also consulted about what type of microfluidic chip suit us the best. We had tested our device parts and found some troubles regarding the chip we used. Our first version uses PDMS microfluidic chip but apparently when we tested it in our centrifuge, it burst. Therefore we went to Ph.D. Chen-Hsun Weng who suggested us to use paper-based chip because it can do blood separation. He also said PDMS is harder to customize and is quite inefficient. He then taught us to use the engraving machine for the acrylic disk.

Enterprise visit

Just because an idea is good does not always mean it will sell well in the market. Our product may be designed and modified in the laboratory and adjusted to maximize its performance. However, we needed advice from potential stakeholders to ensure our product will meet real-world demands. We need to interact with industries to understand more about the industrial environment and current market situation. So, in order to refine our idea into a product suitable for the market, we visited several enterprises.

GeneFerm Biotechnology Co., LTD.

Geneferm is a leading fermentation company, that focuses on fermented fungi, microbes and also probiotics. We visited Geneferm to learn more about the criteria we need to meet before our product can enter the market. At this stage, we were still considering whether to market our product as a drug or probiotic.

From our meeting with Miss Erin Wu and Mr Eugene Wu, we learned:

Quality control of a living cell on a medication
Food Industry Research and Development (FIRDI) help in inspection of the supplement
Comparison between food and medication process and regulation
The risks if we do not apply patent for our drug or medical device

Moreover, they suggested us three things:

Determine the usage of product like the age group and delivering product
Take into account the law and regulations since Taiwan does not have proper gene-editing regulations especially toward the biotherapeutic drug
Education toward GMO usage

By their suggestions, we conducted survey for our drug method delivery and classified approximate age of ESRD patients who will consume our biotherapeutic drug (Data can be seen in our entrepreneurship. Also, because of them, we also planned to pay a visit to IPO (Intellectual Property Office) to learn more about patents.

GenMont Biotech Inc.

Genmont is a leading probiotic company in Taiwan, where we had our first enterprise visit and we were fortunate enough to meet Genmont’s Miss Tsai, Wan-Hua, Miss Mei-Ling Wang, Miss Janette Chen. As this enterprise visit was made when we still wanted our product to be a probiotic, our main purpose of visiting GenMont is to learn about how probiotic is made, how quality management is done and regulations we need to obey in applying this product to the market.

They were kind enough to give a short talk about how their company works and how their research and development works. They also talked about their process in entering their product into the market. This way, we were able to get a glimpse of how the company is able to build from the ground up, and inspired us to create a business plan for our products.

Through this visit, we received a lot of feedback and realized we need to much more research, not only on developing our product, but also more research on many other fields. We need to start thinking about how to apply this project into a real life situation. We need to consider the regulations and consider adding our product into the National Health Insurance.They also mentioned about the safety assay on how our engineered E.coli is and by their suggestions, we optimized our kill switch plan and run a functional check to make sure that our engineered E.coli is safe.

Synbio Tech Inc.

Synbio Tech Inc., a company focusing on probiotic powder and healthcare products. We got a chance to meet Mr. Jin-Seng Lin, Miss I-Ju Chang and Miss Erica Chang from Synbio Tech. Our purpose is to have valuable insights on how we are going to market the product and manufacture process. We implemented the marketing suggestion from Synbio Tech to expand our products marketing and business plan. It was an enlightenment meeting, we received a lot of suggestions on how we should market our products:

Establish the key points of the products
Marketing Promotion has to be different since our products are different and have a specific target. They also mentioned our drug marketing is also limited as we have target consumers. However, they did mention B2B (Business to Business):

Join medical conferences to meet potential business partners and auiliences
The website design must be appealing and have a clear description
White paper to attract investors
Proper and effective advertisements
Drug must fulfill cGMP requirements, and have their form. They told us that from powder, liquid and tablets form of the drug, the most popular one is the powder sachet but to determine which one is suitable for us, we need to conduct a survey for prices and forms. By their suggestions, we started our survey about public opinions.

Winston Medical Supply Co.

We went to Winston Medical Supply Co. to learn about the drugs market and the steps needed to be taken for a drug to be in the market. We were able to meet with Yu-Cheng Wang, CEO of the company and also Yi-Ching Chen, Marketing Director of Winston. We received a lot of feedback toward our wet and entrepreneurship part. He agreed that CKD is a serious problem in Taiwan and uses up a lot of money to deal with the treatments, but they were concerned about how we are going to maintain the effectiveness of Can gene knockout, but after we showed them how we did a functional test, they then suggested it needs to be optimized later when we already finished with the fermentation and packaging part in the future.

Moving on to the marketing part, we showed them our CreSolve living therapeutic drug flowchart that includes the few steps we need to take in order to make our living therapeutic successful in the market. Wang CEO emphasized that we need to start from API (Active Pharmaceutical Ingredients), and it needs to be divided into 4 parts which are Regulation, API, Formulation and Preclinical. After that, we then can develop our drug more precisely. Through their recommendations, we came up with a new flowchart of our CreSolve living therapeutic drug:

We also asked whether they can be our potential partners regarding drug manufacturing in the future, they said it is possible as long we can show them the final prototype of our CreSolve living therapeutic drug accompanied by government approval and research data.

NARLabs (National Applied Research Laboratories)

Founded by the government, NARLabs is one of the leading research centers in Taiwan. We had the opportunity to visit the lab and consulted our business model with NARLabs’ startup team, which is aimed at helping new startups to build better business model and also provide fundings to potential startups. During the visit, we talked about the overall project of OMG and also showed them the current business model we had.

The meeting was successful and we gained a lot from NARLabs, mostly from the business part:

Currently, laws in Taiwan on engineered bacteria are quite strict and there are still some laws under discussion. So, we should pay more attention to the laws and make sure we are always up-to-date with the latest news.
Coating the sensing bacteria on PDMS chips may be a good idea, but we need to be extra careful about the bacteria because most bacteria have a certain condition that has to be met in order to survive.
When developing the business model, sometimes it is also important to consider users’ experiences into the model. For example, where will the sensing device best serve our patient and if the device is safe enough to let the patients operate it by themselves.

Government Association

Laws and regulations set by the government, especially when it comes to GMO products, can sometimes be tricky. In addition to the fact that we wanted to potentially launch our own start-up based on this project, we needed to make sure that we are not breaking any rules. To make sure we are on the right track, we contacted several government agencies.

IPO
TFDA

IPO (Intellectual Property Office)

Due to a suggestion made by GeneFerm, we visited the Intellectual Property Office. We wanted to consult the expert and commissioner about the procedure of the patent application. We also wanted to know if there will be more regulations and laws to ensure the uniqueness and specificity of our product after the living therapeutic drug is marketed. In addition, we also wanted to understand why there are so many bio-related restrictions.

The director of IPO Tainan Branch gave us a patent-related course. He taught us the query skills of our patent search mechanism. The expert also reminded us to pay attention to the relevant application procedures. From category, item objects to cost, they all have clear explanations. Even the years, nationality, and method of application have different regulations, too. Due to its unique operations and novel ideas, the director recommended us to apply the “invention” patent for our living therapeutic drug. As for our CreSense sensing device, it’s suitable to apply for a utility model patent because the device has new features and new testing projects after our team’s improvement.

TFDA (Taiwan Food and Drugs Administration)

By phone call:

Through GenMont’s suggestion, we contacted Taiwan Foods & Drugs Administration to propose our project. They were very clear in the difference between a probiotic and drug. They said that because we wanted to say our product has pharmacological effects, we need to market CreSense as a drug instead of a probiotic.

2019 NCKU iGEM OMG Survey

Genetically Modified Organisms (GMOs) are becoming more and more prevalent in our society due to its potential in many different fields, including pharmaceutical field. There is a large amount of misconceptions and controversies surrounding GMOs. Despite the majority of scientists and researchers pushing for GMOs, it seems like the public are getting more and more wary about it.

In order to have a better idea of how the public perceives GMOs in the context of our Oh My Gut project, we developed an opinion survey about GMOs and their use in the treatment of CKD. We were fortunate enough to be able to spread this survey to international citizens. We received responses from Singapore, Malaysia, Indonesia, Japan, the Netherlands, Germany, Ukraine, Spain, Mexico, China, Canada, India and Greece.

Population Sample

From the responses we got, we know that nearly 80% of responses were comprised of those aged 18 - 25 and 41 - 65 (see Fig. 1). It was relieving to know that a large majority has received high school-level education at the very least (see Fig. 2), although only 19% were of scientific backgrounds (see Fig. 3).

Fig. 1. Age distribution

Fig. 2. Highest education level

Fig. 3. Background

Knowledge on CKD

First, we wanted to assess the sample population’s general knowledge of Chronic Kidney Disease. Thus, we established several questions to learn more about their level of information. It was quite a surprise to us that only 47% of them had heard of CKD (see Fig. 4) and only 10% admits to being quite knowledgeable about CKD (see Fig. 5). When asked about current treatments for CKD (see Fig. 6), 58% admitted to knowing nothing. The most well-known method was dialysis and kidney transplant, with 22% and 11% responses respectively. Other responses include medicine, diet control, controlling blood pressure/sugar and active charcoal.

From these responses, we could deduce that there is still a lack of education and knowledge when it comes to Chronic Kidney Disease. The responses inspired us to launch a workshop aimed at elementary students, to educate them about kidneys with a hands-on approach. (See public engagement)

Fig. 4. Have you heard of CKD?

Fig. 5. What is your understanding of CKD? (5 being an expert on CKD)

Fig. 6. What are the current treatments for CKD?

Living Therapeutic Acceptance

Second, we wanted to assess the sample population’s acceptance when it comes to living therapeutic. Thus, we established a few questions to understand more about their stance on living therapeutic (engineered bacteria used as medical treatments). Only 37% were supportive of genetic engineering, while 31% were considerably neutral (see Fig. 7). 39% approved the development of ‘gene-edited’ bacterial drugs, while only 34% agreed to use said bacterial drugs.

From these responses, we could deduce that there is still a large percentage of people who do not fully support or are neutral about gene editing, especially when it comes to gene-edited bacterial drugs. As such, we can conclude that there is still a long way to go before gene-edited pharmaceutical products like CreSolve (our live therapeutic drug) is able to hit the market. However, we are still optimistic that given enough time and education, live therapeutics can become a staple in medical treatments.

Fig. 7. What is your level of support for ‘Genetic Engineering’ or ‘Genetic Modification’?

Fig. 8. What is your level of support for the development of "gene-edited" bacterial drugs?

Fig. 9. Will you agree to use "gene edited" bacterial drugs?

p-Cresol Detector Acceptance

Last, we wanted to assess the sample population’s acceptance when it comes to utilizing a p-Cresol Detector. Thus, we established a few questions first to understand the current situation and whether or not there is a need for this detector. 38% have ever done a kidney function test (see Fig.10), but only a mere 9% has ever done a self-paid uremic toxin test (see Fig. 11). However, we cannot know for sure if the reason there is only a small percentage of people doing uremic toxin tests is because of lack of knowledge or lack of need.

We performed this survey to understand more about what the public wants and needs when it comes to a uremic toxin detector, to further understand CreSense, our blood p-Cresol quantification device’s value in the market. Most are concerned about the accuracy and cost of the device, with 67% only accepting the device if the price-tag is below 50 USD. That being said, we are happy to say that each CreSense test will cost less than $2, which is much lower than the public’s estimation.

Fig. 10. Have you ever did a "Kidney Function Test" (Ex: Creatinine test)?

Fig. 11. Have you ever did a "self-paid uremic toxin test"?

Fig. 12. Which of the following are you concerned about when choosing a "blood uremic toxin detector"? (Multiple choice)

Fig. 13. What amount of "self-paid detection fee" can you accept? (Amount in USD)

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+                                </p>
+                            </div>
+                            <div id="slide1-chapter1" class="popout">
+                                    <div title="Click to read more" id="coll1" role="button" tabindex="0"  class="collapsible active main-nav-link" linkedidchapter="slide1-chapter1">
+                                        RDT Need
+                                    </div>
+                                <div class="collapsible-content">
+                                    <div class="collapsible-content-wrapper">
+                                        <h3>Question: Which challenge is iGEM Leiden 2020 going to take on?</h3>
+                                    </div>
+                                    <div class="content-wrap">
+                                        <div class="question-hp">
+                                            <h2 > Input</h2>
+                                            <div class="question-content">
+                                                <p>
+                                                    <em>Our team started the iGEM experience with a very open attitude, hoping to address an important societal issue. Our team decided to work in the field of infectious diseases. As we dug into literature and talked to experts, we aimed to identify a need in this vast field. </em>
+                                                </p>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/c/c4/T--Leiden--WHO-emblem.png" alt="Picture of this person">
+                                                </div>
+                                                <div >
+                                                    <h4> World Health Organization </h4>
+                                                    <p>
+                                                        As part of their effort in emergency preparedness and response, the WHO keeps a record of the outbreaks that occur yearly. The latest outbreaks include Yellow fever,  influenza A virus, Ebola virus, Plague, MERS-CoV, Measles, Dengue, as well as SARS-CoV-2. Certain diseases, such as Ebola, are recurrent in tropical and Subsaharan regions<a class="hyperlink main-nav-link" linkedidchapter="slide1-chapter9"><sup>1</sup></a>. <a class="hyperlink" target="_blank" href="https://www.who.int/news-room/fact-sheets/detail/yellow-fever">Yellow Fever</a><a class="hyperlink main-nav-link" linkedidchapter="slide1-chapter9"><sup>2</sup></a> is endemic in Africa and Central and South America, whereas the endemic regions affected by <a class="hyperlink" target="_blank" href="https://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue">Dengue</a><a class="hyperlink main-nav-link" linkedidchapter="slide1-chapter9"><sup>3</sup></a> are even larger. These outbreaks of diseases need to be addressed with funds but also medical developments. This is all the more important in regions with fewer resources.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/e/e1/T--Leiden--LitteratureSources.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>McNerney, R. (2015). Diagnostics for developing countries. Diagnostics, 5(2), 200-209<a class="hyperlink main-nav-link" linkedidchapter="slide1-chapter9"><sup>4</sup></a>.  </h4>
+                                                    <p>
+                                                        Lower-income countries have a higher incidence and prevalence of communicable diseases, because of a lack of correct diagnosis and follow-up treatment for the patients, due to geographical or financial reasons. As a consequence, they often face difficulties preventing the further transmission of these diseases.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/c/c1/T--Leiden--Permata.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Dr Assica Permata, M.D. currently working on TB in a research environment </h4>
+                                                    <p>
+                                                        Dr Permata told us about the situation in Indonesia, where patients in large cities usually could get tested. However, in smaller cities, where the laboratory facilities are not optimal, the samples have to be sent to larger facilities and patients may have to wait days to weeks for the results.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/e/e1/T--Leiden--LitteratureSources.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Peeling & Mabey, 2010<a class="hyperlink main-nav-link" linkedidchapter="slide1-chapter9"><sup>5</sup></a>.</h4>
+                                                    <p>
+                                                        In the developing world, there is a need for point of care tests, as they can help speed up the diagnosis of bacterial, parasitic, and viral diseases. Additionally, the quality of the tests has to be improved. Systems for quality control and improving training in the use of the kit can help improve the quality of the tests.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/1/16/T--Leiden--Robin_van_Houdt.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Robin van Houdt, microbiologist at the Dutch Association for Medical Microbiology and the UMC Amsterdam</h4>
+                                                    <p>
+                                                        Robin van Houdt told us that RDTs are also very useful in developed, high-income countries where hospitals dispose of sophisticated laboratories. RDTs could be used to tests patients upon entry in the hospital, for instance, identifying the patients that should be treated in isolation. This could help save a lot of time and money, and is better for the patient’s wellbeing. RDTs could also be used to quickly test an entire ward if an infection does occur. This could then prevent spread to other parts of the hospital.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/3/33/T--Leiden--Huram_Konjen.png
+                                                    " alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Huram Konjen, Chief executive officer of Dianox</h4>
+                                                    <p>
+                                                        Mr. Konjen told us that the need to improve diagnostics lies in the need to address and reduce the elevated costs associated with testing. These costs are mainly lab costs such as equipment and the staff.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                        </div>
+                                        <div class="integration-hp">
+                                            <h2> Integration</h2>
+                                            <p>
+                                                Infectious diseases are the most important <span class="highlight">enemy</span> of the health of <span class="highlight">humankind</span>, translated as seasonal colds, urinary infections, but also haemorrhagic fevers, respiratory affections or septic shocks.
+                                            </p>
+                                            <p>
+                                                When our team first sat down around a table to discuss the purpose of our project, a very obvious, threatening situation was cooking on the other side of the planet. The <span class="highlight">COVID-19</span> pandemic seeped through each of our conversations and interfered with our habits and way of life. It reminded us of the damage and <span class="highlight">chaos</span> that a few nano/micrometers of biology can cause in entire populations.
+                                            </p>
+                                            <p>
+                                                Particularly in the middle and low resource areas, the increased emergence of these outbreaks and the <span class="highlight">lack</span> of sufficient medical <span class="highlight">resources</span> yield an important death toll, even for preventable and treatable diseases<a class="hyperlink main-nav-link" linkedidchapter="slide1-chapter9"><sup>6</sup></a>.
+                                            </p>
+                                            <p>
+                                                Our team therefore decided to take on the challenge of developing an economical and accessible <span class="highlight">rapid diagnostic test</span> (RDT) for infectious diseases.
+                                            </p>
+                                            <p>
+                                                Rapid diagnostic tests can be used with minimal equipment and are suitable for <span class="highlight">emergency</span> situations, where low resources are available, but not only. The <span class="highlight">speed</span> of the tests is also particularly appreciated as delays in diagnosis can result in the poorer prognosis of the patients. For some neglected or less prevalent infectious diseases, there is a true, urgent need for more specific, accurate, and <span class="highlight">accessible</span> diagnostic tools. Diagnosis of other, more prevalent diseases such as Malaria, require more qualitative tests, in a market flooded with low-cost tests.
+                                            </p>
+                                        </div>
+                                    </div>
+                                </div>
+                            </div>
+                            <div id="slide1-chapter2" class="popout">
+                                    <div   title="Click to read more"id="coll2" role="button" tabindex="0"  class="collapsible main-nav-link" linkedidchapter="slide1-chapter2">
+                                        Science
+                                    </div>
+                                <div class="collapsible-content">
+                                    <div class="collapsible-content-wrapper">
+                                        <h3>Question: Developing a rapid diagnostic test for infectious diseases: where do we start?  </h3>
+                                    </div>
+                                    <div class="content-wrap">
+                                        <div class="question-hp">
+                                            <h2 > Input</h2>
+                                            <div class="question-content">
+                                                <p>
+                                                    <em>The first step to develop a rapid diagnostic test is to determine the technical, scientific means at our disposal and to compare it to existing methods, to identify a starting point. To do so, our team turned to our predecessors in the iGEM community, in the hope to learn from their experience and launch our ambitious quest.  </em>
+                                                </p>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/5/53/T--Leiden--NiekSavelkoul.png" alt="Picture of this person">
+                                                </div>
+                                                <div >
+                                                    <h4> Niek Savelkoul, iGEM 2017 Wageningen Mantis & Founder of Scope Biosciences </h4>
+                                                    <p>
+                                                        Niek shared his experience in the iGEM 2017 Mantis project, in which they attempted to develop a multiplex rapid test for infectious diseases. However, they did not manage to get a functional kit. He said that using a cell receptor sensor presented too many limitations, such as a delay due to the transcription and the fact that it contained living material. He suggested that a cell-free system would be preferred.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src=" https://static.igem.org/mediawiki/2020/9/94/T--Leiden--Janneke_Wijgert.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Prof. dr. Janneke van de Wijgert, professor in epidemiology UMC Utrecht & Liverpool </h4>
+                                                    <p>
+                                                        According to professor Janneke van de Wijgert, in general, a molecular-based diagnostic kit has an advantage over antigen/antibody-based or chemical biomarker-based kits when considering reliability. However, reliability depends on the type and complexity of the disease.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/6/65/T--Leiden--Peter_Bredenbeek.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Dr Peter Bredenbeek, assistant professor in Virology LUMC  </h4>
+                                                    <p>
+                                                        With Dr. Bredenbeek we discussed which scientific considerations were important. He stated that to be successful, our kit should be at least as sensitive as PCR, which is able to detect up to 4-5 copies/mL of sampled blood. He also encouraged us to include a positive and negative control in each of the kits.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/d/d0/T--Leiden--Thomas_Caltagirone.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Thomas Caltagirone, CEO of Alpagen LLP</h4>
+                                                    <p>
+                                                        We discussed with Dr. Caltagirone his publication of 2018, on a technique that is able to cause a color change in the reaction with the help of a DNAzyme, called the GQ-EXPAR system<a class="hyperlink main-nav-link" linkedidchapter="slide1-chapter9"><sup>7</sup></a>. He told us that the amplification of the target in the tube would help to reduce false positives and increase the intensity of the colorimetric output.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-wrapper-stay-flex-no-space">
+                                                    <div class="figure-container width40-no-margin">
+                                                        <img src="https://static.igem.org/mediawiki/2020/3/30/T--Leiden--Armand_Paauw.png" alt="Picture of this person">
+                                                    </div>
+                                                    <div class="figure-container width40-no-margin">
+                                                        <img src="https://static.igem.org/mediawiki/2020/e/ec/T--Leiden--Hans_van_Leeuwen.png" alt="Picture of this person">
+                                                    </div>
+                                                </div>
+                                                <div>
+                                                    <h4>Dr Armand Paauw, Scientist at TNO Defence, Security and Safety, & Dr Hans van Leeuwen, Senior Scientist at TNO</h4>
+                                                    <p>
+                                                        LAMP is a factor 5 to 10 less sensitive than qPCR. This is problematic for LAMP because qPCR will always be picked over LAMP in a lab environment. This means that if your kit is to be used in a lab, then it has to compete with qPCR and be at least as good. If your kit is meant for a setting outside of the lab (point-of-care), it is acceptable to lose some sensitivity. The point-of-care nature makes up for the loss in sensitivity.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/6/69/T--Leiden--EPFL_Vitest.jpg" alt="Picture of  EPFL">
+                                                </div>
+                                                <div>
+                                                    <h4>iGEM EPFL 2019 ViTest</h4>
+                                                    <p>
+                                                        Thereafter, we reached out to the iGEM 2019 team from EPFL, that worked on developing a sensor for wine diseases as they used the RPA technique for amplification. They told us that RPA is highly specific and sensitive, but that as a result contaminations can interfere with the results. They suggested using the TwistDX kit for RPA.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                        </div>
+                                        <div class="integration-hp">
+                                            <h2> Integration</h2>
+                                            <p>
+                                                At the start of our project, we reached out to the 2017 iGEM Mantis project, to understand the challenges they faced and to identify our <span class="highlight">starting point</span>. One of their challenges, integrating living cells with an antibody library in a test kit, was not feasible. Our team, therefore, decided to opt for a <span class="highlight">cell-free system</span>, comprised of enzymes and rather stable nucleic acids. This also enabled to bypass the challenge that antigen tests may face and allows to directly identify the pathogen using <span class="highlight">molecular</span> techniques.
+                                            </p>
+                                            <p>
+                                                Literature  also suggested that the RPA method is more <span class="highlight">sensitive</span> than PCR (the golden standard, and reference technique for many infectious diseases) in a controlled environment<a class="hyperlink main-nav-link" linkedidchapter="slide1-chapter9"><sup>8</sup></a>. Additionally, RPA is a good option as it does not require a power source and would enable <span class="highlight">equipment-free</span> use.
+                                            </p>
+                                            <p>
+                                                Finally, technical considerations pushed forwards by many parties was the need for a qualitative, easily-detectable and foolproof <span class="highlight">output</span>, which would leave no room for interpretation. Our team therefore got inspired by the common ELISA tests. By using a peroxidase DNAzyme with hemin, positive samples would undergo an immediate and very clear <span class="highlight">color change</span>. Our team has also thought about the integration of the <span class="highlight">controls</span> in the kit as seen on our <a class="hyperlink" href="https://2020.igem.org/Team:Leiden/Hardware">Hardware</a> page
+                                            </p>
+                                        </div>
+                                    </div>
+                                </div>
+                            </div>
+                            <div  id="slide1-chapter3" class="popout">
+                                <div title="Click to read more" id="coll3" role="button" tabindex="0" class="collapsible main-nav-link" linkedidchapter="slide1-chapter3">
+                                    Application
+                                </div>
+                                <div class="collapsible-content">
+                                    <div class="collapsible-content-wrapper">
+                                        <h3>Question: How can we identify a niche in the vast and complex field of infectious diseases? </h3>
+                                    </div>
+                                    <div class="content-wrap">
+                                        <div class="question-hp">
+                                            <h2 > Input</h2>
+                                            <div class="question-content">
+                                                <p>
+                                                    <em>The preliminary steps in our project indicated that there is a need for more and better diagnostics. Nevertheless, the need may differ depending on the disease and the sociogeographical situation of the patient. In the quest for an application, our team reached out to patients and experts in the field to understand where the specific medical, but also societal needs and challenges lie, for each of the diseases. </em>
+                                                </p>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/6/65/T--Leiden--Peter_Bredenbeek.png" alt="Picture of this person">
+                                                </div>
+                                                <div >
+                                                    <h4> Dr Peter Bredenbeek, assistant professor in Virology LUMC </h4>
+                                                    <p>
+                                                        The first pathogen we naturally thought of was the pathogen responsible for the current pandemic, the coronavirus, as no molecular test had yet been approved. However, Dr. Bredenbeek strongly discouraged us from choosing SARS-CoV-2 as an application. We would be competing with very large companies that possess extensive resources and large networks. These companies are racing for financial gain and scientific novelty in a highly pressured environment. Aligned with iGEM's advice and expectations, we decided not to linger on this topic and instead, look into other applications.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="
+                                                    https://static.igem.org/mediawiki/2020/f/f5/T--Leiden--Rene_Paulussen.png" alt="Picture of this person">
+                                                </div>
+                                                <div >
+                                                    <h4> René Paulussen, managing director Mondial Diagnostics </h4>
+                                                    <p>
+                                                        Our team set out to further research other pathogens, of which Vibrio cholerae. However, Mr. Paulussen discouraged us from developing a test kit for this disease. When an outbreak occurs in a community, only the first patients are diagnosed. Other patients with the same symptoms are treated for cholera without further testing. This is due to the epidemic nature of cholera. The cholera market is, therefore, an extremely low margin market for high development costs, which would not be viable for a project like Rapidemic.
+                                                    </p>
+                                                </div>
+                                            </div>
+<!-- Content deleted per team's request - Traci Haddock-Angelli
+-->
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/2/23/T--Leiden--Lieselotte_Hardy.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Dr Lieselotte Hardy, Doctor at Institute of Tropical Medicine Antwerp, Belgium </h4>
+                                                    <p>
+                                                        Dr. Hardy focuses on infectious diseases and their diagnosis and has worked on projects in Sub Saharan Africa and Asia. She mentioned that the diagnosis of bacterial bloodstream infections is still insufficient and that a rapid diagnostic test (RDT) for these infections would be fruitful. However, she also mentioned that in the case of bacterial sepsis, the concentration of the bacterial agent can be very low. This input was confirmed by one of Hardy's colleagues, who is a medical doctor. While there is a need for better diagnosis of this affection, even in hospital settings, diagnosis of sepsis would require multiplex testing of various pathogens, which might not be accommodated by our kit.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/a/a2/T--Leiden--Heleen_Koudijs.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Dr Heleen Koudijs, Tropical doctor</h4>
+                                                    <p>
+                                                        Dr. Koudijs also discussed TB as a potential disease our technology could be applied to. However, she mentioned that Genexpert has good control over the market. A drawback Genexpert has is that the kit is quite expensive.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <h3>Mosquito-born diseases</h3><br>
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/a/a2/T--Leiden--Heleen_Koudijs.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Dr Heleen Koudijs, Tropical doctor</h4>
+                                                    <p>
+                                                        Dr. Koudijs proposed several mosquito-borne diseases, one of these is Malaria. According to Dr. Koudijs, the market for RDT for malaria is quite saturated. There are a lot of cheap RDT's available for malaria. The reason why they are so cheap is because the companies are funded by organizations such as the WHO, Gates Foundation, and other NGO's. As a consequence, malaria might not be the best disease to focus on.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/0/0f/T--Leiden--patients.png" alt="Patient icon">
+                                                </div>
+                                                <div>
+                                                    <h4>Dengue and Malaria patients</h4>
+                                                    <p>
+                                                        We questioned patients diagnosed with Dengue (3) and Malaria (3) in Honduras, Argentina, Zambia, Congo, Costa Rica, and Indonesia about their diagnostic procedures. Some of the patients stated that they experienced difficulties in reaching a doctor to get tested, demonstrating that access to healthcare is not always easy. The patients experienced a very slow and inaccurate diagnosic procedure of the dengue virus and stated that it needs to be improved. Malaria patients also had to undergo repeated testing, even when tested in centers with experienced doctors. The patients expressed that they would prefer a quicker diagnostic procedure that would require less blood sampling.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/2/21/T--Leiden--Helene_van_Oorschot.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Hélène van Oorschot, Student in medicine</h4>
+                                                    <p>
+                                                        With Mrs. van Oorschot we discussed malaria and dengue as potential applications. She discouraged mosquito-borne diseases in general because if there is an epidemic, quarantine would not help. Apart from this, with malaria as an application, our kit would also compete with the medicine itself. This is because malaria medicine is cheap and readily available. For example, if the patient has the symptoms of malaria, but microscopy does not diagnose malaria, the patient is still given malaria medicine. In addition, testing for dengue is questionable as there is no cure available. Patients can therefore only be treated for their symptoms, rather than the source of disease, such as preventing dehydration.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <h3>Disease X and Epidemic preparedness</h3> <br>
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/5/5b/T--Leiden--_Pim_Martens.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Professor Pim Martens, Maastricht Sustainability Institute, director of the International Centre for Integrated assessment and Sustainable development (ICIS), School of Business and Economics, founder of AnimalWise and member of House of Animals, member of Dutch Health Council</h4>
+                                                    <p>
+                                                        Professor Martens worked on predicting the spread of Malaria and the associated risks. He told us that Malaria is still a very important disease to focus on in diagnostics as it is multifactorial and complex. Deforestation, increasing travel behavior, climate change, intensive farming and the increase in population density are increasing the emergence and the spread of novel pathogens, likely from zoonotic origin. Therefore, when we asked him which pathogen he would like to detect he responded:
+                                                    </p>
+                                                    <p>
+                                                        "I would go for the one we don't know yet"
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-wrapper-stay-flex-no-space">
+                                                    <div class="figure-container width40-no-margin">
+                                                        <img src="https://static.igem.org/mediawiki/2020/3/30/T--Leiden--Armand_Paauw.png" alt="Picture of this person">
+                                                    </div>
+                                                    <div class="figure-container width40-no-margin">
+                                                        <img src="https://static.igem.org/mediawiki/2020/e/ec/T--Leiden--Hans_van_Leeuwen.png" alt="Picture of this person">
+                                                    </div>
+                                                </div>
+                                                <div>
+                                                    <h4>Dr Armand Paauw, Scientist at TNO Defence, Security and Safety, & Dr Hans van Leeuwen, Senior Scientist at TNO</h4>
+                                                    <p>
+                                                        The two scientists at TNO told us that influenza would be a good application, since this is a rapidly mutating virus and has potential to cause an epidemic/pandemic. Besides this, the high mutation rate is something that can be addressed well by the modular nature of the kit. However, one should then be able to prove that the test can be quickly used for various diseases and, by extension, adapted to novel diseases.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/7/7f/T--Leiden--Willem_Mees-min.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Willem Mees van der Bijl, Director IDE Netherlands at IDE Group</h4>
+                                                    <p>
+                                                        Mr. Van der Bijl mentored us on the kit development. Rather than trying to implement one product that can detect any pathogen, he advised focusing the development effort on a specific diagnostic application at first and extending the application later to the diagnosis of other diseases.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                        </div>
+                                        <div class="integration-hp">
+                                            <h2> Integration</h2>
+                                            <p>
+                                                A <span class="highlight">DNA/RNA sensor</span> could be adapted to any human infectious disease. Soon after reaching out to the experts in the field of infectious diseases, our team realized that identifying a <span class="highlight">niche</span> in the field of diagnostics of infectious diseases would require us to balance the science of our kit with many <span class="highlight">external factors</span>. These, for instance, include the medical need for an RDT, the patient's preferences, the identification of a gap in the diagnostic market, but also the feasibility of the implementation, due to regulation and logistics.
+                                            </p>
+                                            <p>
+                                                Our team was driven by a desire to address a societal and humanitarian need for better diagnosis. The input of the patients was triggering, as it made us very invested in improving the diagnostic procedures. Pinpointing an application pushed us to acknowledge and work with the <span class="highlight">qualities</span> and the <span class="highlight">limitations</span> of the science of our kit, to inherently match its application. While we allowed ourselves to aspire to ambitious goals, we made it a prime point in this project to identify a niche and an application that would be realistic and viable.
+                                            </p>
+                                            <p>
+                                                At first, by focussing on <span class="highlight">specific diseases</span> such as Lyme disease, Cholera, bloodstream or urinary infections, and TB, our team aimed to respond to a specific diagnostic need. However, we then soon realized that when doing so, we were positioning ourselves in direct <span class="highlight">competition</span> with the sensitivity, cost, quality, and accuracy of the current methods of diagnosis of these diseases, without being certain that our kit would be able to truly answer an unmet need.
+                                            </p>
+                                            <p>
+                                                While conducting more integrated and holistic research, our team looked into current diagnostic methods for <span class="highlight">mosquito-borne</span> diseases such as Dengue, Yellow Fever, and Malaria. Patients and doctors confirmed that there are struggles with the detection of these diseases, particularly prevalent in tropical zones. Today, these diseases affect hundreds of millions of people each year. It is predicted that these diseases will likely spread towards the North as the effects of <span class="highlight">climate change</span> will force the vectors of these diseases upwards, affecting even more people. However, these diseases do  <span class="highlight">not</span> progress through direct <span class="highlight">human-to-human transmission</span>. This means that quarantine measures based on test results will not have any influence on the spread of the disease. A rapid diagnostic test could replace the "golden standard" diagnosis of these diseases in certain low-income areas. However, as many rapid tests for Malaria have already been developed, it may be unconstructive to compete with  diagnostic tools already on the market. As a consequence, we were not completely conviced that this application would be the optimal niche for our rapid and modular application.
+                                            </p>
+                                            <p>
+                                                We then took a step back an reflected on the scientific content of the tests we had imagined. The use of <span class="highlight">primers</span> in a molecular test would entail that they can be replaced for any pathogen, emphasizing the kit's potential for <span class="highlight">modularity</span>. Therefore, we presented a novel idea to the experts, which was received with great enthusiasm: tackling <span class="highlight">novel outbreaks</span> with epidemic potential at their source to prevent their spread. However, they warned that it is difficult to convince stakeholders in the field of a modular idea, as it might raise skepticism on the feasability of such an ambitious endeavour. Therefore, our team looked into diseases that have great pandemic potential, which rapidly led us to <span class="highlight">respiratory RNA viruses</span>, such as the group of Orthomyxoviridae and Coronaviridae. These pathogens are known to cause disease and <span class="highlight">mutate quickly</span>, making them very likely to cause a next great outbreak. Our kit could be used to rapidly address the need for tests, even in the most remote and low resource areas.
+                                            </p>
+                                        </div>
+                                    </div>
+                                    <div class="time-line-hp">
+                                        <div class="time-line-content">
+                                            <h3>Timeline</h3><br>
+                                            <p> Exploring the needs in rapid diagnostics  →   Mosquito-borne diseases   →  Disease X  →  Respiratory-borne RNA viruses</p>
+                                        </div>
+                                    </div>
+                                </div>
+                            </div>
+                            <div id="slide1-chapter4" class="popout">
+                                <div title="Click to read more" id="coll4" role="button" tabindex="0" class="collapsible main-nav-link" linkedidchapter="slide1-chapter4">
+                                    Users and User-friendliness
+                                </div>
+                                <div class="collapsible-content">
+                                    <div class="collapsible-content-wrapper">
+                                        <h3>Questions: Who is going to use our kit? Where is our kit going to be used? </h3>
+                                    </div>
+                                    <div class="content-wrap">
+                                        <div class="question-hp">
+                                            <h2 > Input</h2>
+                                            <div class="question-content">
+                                                <p>
+                                                    <em>From an accessibility viewpoint, self RDTs are optimal as they do not require medical assistance and can be distributed and sold in pharmacies, directly to the population. We interviewed patients from different areas of the world, business players and doctors that have worked in areas with limited lab or hospital access to understand whether self-testing is the most appropriate option. </em>
+                                                </p>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/8/8a/T--Leiden--Sophie_van_Baalen.png" alt="Picture of this person">
+                                                </div>
+                                                <div >
+                                                    <h4> Dr Sophie van Baalen, Researcher team medical technology for Rathenau institute </h4>
+                                                    <p>
+                                                        Even though we aimed our kit to be used by patients, we did not only discuss patients as possible end-user with Dr van Baalen. According to her, the benefit of having the patient perform the test themselves is that there is no need for professionals to perform them. However, the benefit of having professionals handling the kit is that you have better quality control and immediate follow-up care. Moreover, it enables the collection of epidemiologic data from the tests. In the setting of outbreaks of infectious diseases, this crucial information would enable real-time monitoring of the spread.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/0/0f/T--Leiden--patients.png" alt="Patient icon">
+                                                </div>
+                                                <div>
+                                                    <h4>Patients: Malaria, TB, Dengue and SARS-CoV-2 </h4>
+                                                    <p>
+                                                        We first questioned patients (13) from around the world diagnosed with Malaria, Dengue and Tuberculosis to compare the diagnostic need and settings as well as to understand their preferences.
+                                                    </p>
+                                                    <p>
+                                                        When asked whether they would feel comfortable performing a finger prick test or a nasal swab themselves, the vast majority responded that they would not feel comfortable doing so, and prefer to be assisted. We also asked whether they would trust a test performed by a doctor more or less than a self-RDT. Out of the nine people that answered this question, six said that they would trust a self-RDT less than a test conducted by a doctor.
+                                                    </p>
+                                                    <p>
+                                                        We then also asked COVID-19 patients about their diagnostic experience. We found that if a patient does not experience symptoms that are unique or characteristic of a disease, or if the probability of getting the disease is not (very) high, patients do not think of purchasing a test for this specific disease unless they had been advised by their doctor.
+                                                    </p>
+                                                    <p>
+                                                        Additionally, we questioned the risk of self-RDTs for the patients' health. Indeed, if a patient performs a self-RDT and tests positive, the patient would not be in a setting where it can immediately be provided with treatment if necessary. If the patient tests negative, the patient cannot test further for other diseases, nor have access to additional medical care, such as IV fluids or analgesia.
+                                                    </p>
+                                                    <p>
+                                                        Finally, a patient reminded us that in certain countries, social security is a well-structured system that enables reimbursement to the patients. If a patient in these regions self-tests, but then also wishes to visit a doctor for a second opinion, self RDTs might be an additional procedure, thus an additional cost. A solution would be to sell RDTs solely under prescription.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/f/f5/T--Leiden--Rene_Paulussen.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>René Paulussen, managing director Mondial Diagnostics </h4>
+                                                    <p>
+                                                        As it is challenging to bring a testkit to the market, Mr Paulussen discouraged us from making a home self-test right away. Indeed, companies first have to build up and a reputation and credibility. He, therefore, suggested starting by developing the kit for laboratories with limited infrastructure, where the tests can be conducted by minimally trained staff. This way, the quality can be safeguarded and, in turn, improves the credibility and reputation. Later on, the kit can be made more accessible to less/non trained individuals.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/a/a2/T--Leiden--Heleen_Koudijs.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Dr Heleen Koudijs, Tropical doctor</h4>
+                                                    <p>
+                                                        While working in Ethiopia, Dr Koudijs found that a large share of the population is analphabetic. Therefore, she does not trust the patient to perform the test themselves. She thus recommended developing the kit with health centers or health professionals working in posts in rural villages as end-users. They are probably the best way to reach rural villages as they are greatly respected by the locals.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/d/d6/T--Leiden--Eric_de_Koster.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Eric de Coster, Medical coördinator in the General Infectious Disease Control and Travel Advice </h4>
+                                                    <p>
+                                                        Mr de Coster told us about what happens when a patient tests positive for a disease in health centers (GGD) in the Netherlands. The GGD tests the patients, but also gathers the data (results) and sends the anonymized files to the  National Institute for Public Health and Environment (RIVM). Collecting data is crucial as it can help to manage the spread of diseases and subsequently determine decisionmaking on a governmental level.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <h3>How can we then ensure that our kit is userfriendly?</h3>
+                                                <p>
+                                                    <em>Identifying the end-users of the tests is crucial as it is inherently related to the design of the kit and eventually the reliability of the outcome. Therefore, we sought to know which considerations are important in order to build a physical kit and to render it userfriendly and the result unequivocal.</em>
+                                                </p>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/a/a2/T--Leiden--Heleen_Koudijs.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Dr Heleen Koudijs, Tropical doctor</h4>
+                                                    <p>
+                                                        Dr. Koudijs has worked with RDT's during her time in Ethiopia. However, according to her, the corona test kit used by doctors in Ethiopia lacks a clear description and has a very confusing design. This resulted in unnecessary errors and false results. Therefore, Dr. Koudijs highly recommended ensuring that a clear instruction manual (pamphlet) is present as well as a simple, clear kit design.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/6/60/T--Leiden--John_Tonkinson.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>John Tonkinson, Chief Business Development Officer DCN Dx</h4>
+                                                    <p>
+                                                        Mr. Tonkinson told us to make use of engineering to complete the biological limitations that the kit might present. He strongly emphasized anticipating the slightest errors that one could make. The results should also not leave any room for interpretation, as this is a source of errors. Clear color-coding to show the outcome is a good example to prevent interpretation.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/f/f5/T--Leiden--Rene_Paulussen.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>René Paulussen, managing director Mondial Diagnostics</h4>
+                                                    <p>
+                                                        Mr Paulussen also had some remarks about the design of our kit. He proposed to use the KISS strategy (Keep It Simple, Stupid). Therefore, the explanations of the kit should be given in pictograms, such that they can be understood by everyone, regardless of their education level. The different reagents (such as the buffer and the sample) that should be added together should be color-coded as well.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-wrapper-stay-flex-no-space">
+                                                    <div class="figure-container width40-no-margin">
+                                                        <img src="https://static.igem.org/mediawiki/2020/9/9d/T--Leiden--Aldrik_Velders.png" alt="Picture of this person">
+                                                    </div>
+                                                    <div class="figure-container width40-no-margin">
+                                                        <img src="https://static.igem.org/mediawiki/2020/4/43/T--Leiden--Vittorio_Sagiono.png" alt="Picture of this person">
+                                                    </div>
+                                                </div>
+                                                <div>
+                                                    <h4>Professor dr Aldrik Velders, Nanobiotechnology at Wageningen University & Dr Vittorio Saggiomo, Organic Chemistry</h4>
+                                                    <p>
+                                                        The two chemists working on developing microfluidic devices told us that it is important to keep the handling of the device to a minimum and to limit the possibility of contaminations to ensure a reliable outcome.  Thus, ideally, the kit should be as passive as possible and happen in a single reaction tube.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                        </div>
+                                        <div class="integration-hp">
+                                            <h2> Integration</h2>
+                                            <p>
+                                                Certain limitations of self-testing, such as the increased chance of false results due to human error and the absence of appropriate data gathering, indicate that <span class="highlight">patients</span> should probably not be entrusted with the manipulation of the kits themselves.
+                                            </p>
+                                            <p>
+                                                The input gathered indicates that patients as well as doctors and developers think it is best to consider <span class="highlight">trained staff</span> as users of the kits. Patients are not eager to perform medical procedures themselves, even minor ones. The patients overall would not prefer performing a kit from the comfort of their homes as they would like to get proper follow-up care in the case of a severe disease.
+                                            </p>
+                                            <p>
+                                                Out of concern for equality, we do not want to compromise the <span class="highlight">accessibility</span> nor the quality, and instead find the right balance between both. Therefore, our team thinks that the tests could be used by hospital staff, but also NGOs or trained technicians that could be mobilized in the field or in <span class="highlight">crowded areas</span> such as airports and in cities. The kits could also be performed by staff in schools, essential businesses, or elderly homes. Performing tests by trained staff also facilitates data collection for epidemiology, so important in outbreaks of infectious diseases. Trained staff will also be more inclined to properly dispose of the kit, which contains material from a potentially infected patient (see <a class= "main-nav-link hyperlink" linkedidchapter="slide1-chapter7" linkedid="coll7">Disposal</a>).
+                                            </p>
+                                            <p>
+                                                Furthermore, the experts reminded us of certain considerations that, when applied, can help safeguard the <span class="highlight">quality</span> of the test. The test should be made as intuitive, easy and robust as possible. Indeed, our team attempted to minimize the amount of handling by conducting the reactions with buffers that could accommodate the different components and conduct reactions with the least amount of material possible (fewer reaction tubes, centrifugation steps, using generic buffers or adapt the pH).
+                                            </p>
+                                            <p>
+                                                To avoid <span class="highlight">interpretation</span>, experts confirmed that a colorimetric output is a good option. The test would be given along with a color indicator, as well as an integrated positive and negative <span class="highlight">control</span> in the test, with the aim to minimize human error.
+                                            </p>
+                                            <p>
+                                                More about the design of the kit can be found on the <a class="hyperlink" href="https://2020.igem.org/Team:Leiden/Hardware">Hardware</a> page.
+                                            </p>
+                                        </div>
+                                    </div>
+                                    <div class="time-line-hp">
+                                        <div class="time-line-content">
+                                            <h3>Timeline</h3><br>
+                                            <p> Exploring the needs in rapid diagnostics  →   Mosquito-borne diseases   →  Disease X  →  Respiratory-borne RNA viruses</p>
+                                        </div>
+                                    </div>
+                                </div>
+                            </div>
+                            <div id="slide1-chapter5" class="popout">
+                                <div title="Click to read more" id="coll5" role="button" tabindex="0" class="collapsible main-nav-link" linkedidchapter="slide1-chapter5">
+                                    Affordability
+                                </div>
+                                <div class="collapsible-content">
+                                    <div class="collapsible-content-wrapper">
+                                        <h3>Question: How can we ensure that the cost of a test does not compromise the accessibility to all?   </h3>
+                                    </div>
+                                    <div class="content-wrap">
+                                        <div class="question-hp">
+                                            <h2 > Input</h2>
+                                            <div class="question-content">
+                                                <p>
+                                                    <em>Proper healthcare is a basic need, however, it has to be paid for to be sustained. We attempted to understand the cost of exitsting RDTs, and how we can make ours affordable for all.   </em>
+                                                </p>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/5/53/T--Leiden--NiekSavelkoul.png" alt="Picture of this person">
+                                                </div>
+                                                <div >
+                                                    <h4> Niek Savelkoul, iGEM 2017 Wageningen Mantis & Founder of Scope Biosciences </h4>
+                                                    <p>
+                                                        Niek told us that behind projects to improve diagnostics lie a strong philanthropic desire. As many RDTs are developed for low resource areas, the tests cannot be too expensive as they would not be used in the regions in need.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/9/94/T--Leiden--Janneke_Wijgert.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Prof. dr. Janneke van de Wijgert, professor in epidemiology UMC Utrecht & Liverpool </h4>
+                                                    <p>
+                                                        Professor van de Wijgert said that most RDTs are not widely available. In resource-poor countries, almost all tests are considered too expensive.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/6/60/T--Leiden--John_Tonkinson.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>John Tonkinson, Chief Business Development Officer DCN Dx </h4>
+                                                    <p>
+                                                        Mr. Tonkinson told us that typically during pandemics, tests are funded or subsidized by foundations working with local governments (such as the Gates foundation). He told us that they set the cost depending on the budget and that the test kits should then be produced for that price. Therefore, the tests have to be economical and the prices have to be set at the beginning of the development process. He also told us that producing in very large amounts, as is done for Malaria RDTs, enables us to drastically reduce the price per kit.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/b/b5/T--Leiden--VanVugt.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Erik van Vught, Goffin Molecular Technologies</h4>
+                                                    <p>
+                                                        Mr van Vught said that a kit should not cost more than 10€, as determined by the market, or perhaps 12€ if the test is very unique. This price should include the costs of distibution and logistics. However, doing distribution ourselves would jeopardize the value creation out of our sales. Therefore, it is recommended to outsource distribution.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/2/2e/T--Leiden--Dr_Dam.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Dr Dam, Medical doctor </h4>
+                                                    <p>
+                                                        Dr. Dam told us that in The Netherlands tests for this pandemic were paid by the government. For other infectious diseases, the tests are paid by health insurance companies.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/a/a2/T--Leiden--Heleen_Koudijs.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Dr Heleen Koudijs, Tropical doctor</h4>
+                                                    <p>
+                                                        In order to get the cost of the kit low, Dr. Koudijs told us it is important to follow the guidelines of UNESCO, UNICEF, WHO and other NGO's. For many lower-income countries, these organizations fund the purchase of diagnostic tests. In other countries, like Ethiopia, the government pays for medical devices.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/8/8a/T--Leiden--Sophie_van_Baalen.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Dr Sophie van Baalen, Researcher team medical technology for Rathenau institute</h4>
+                                                    <p>
+                                                        Dr. Van Baalen also suggested thinking about strategies to ensure equal distribution during a pandemic. For example by adopting a model in which high-income countries would pay a higher price for test-kits than lower-income countries.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                        </div>
+                                        <div class="integration-hp">
+                                            <h2> Integration</h2>
+                                            <p>
+                                                In a pandemic where the entire world is affected, everyone should have <span class="highlight">access</span> to diagnosis. However, everything has a price, and a business cannot continue to provide products without <span class="highlight">income</span>. Diagnostics should be sold at a very low price as usually they are government-funded, but sometimes also by foundations and NGOs. Therefore, businesses have to work with an immuable, limited budget. An <span class="highlight">economical</span> test would allow governments to be able to <span class="highlight">test more</span>, and repeatedly.
+                                            </p>
+                                            <p>
+                                                An advantage of molecular diagnostics is that they tend to be rather economical. Our team tried to approximate the cost of a single test reaction performed in the lab. The <span class="highlight">cost</span> of a single detection (as determined by the purchase cost of the reagents, sequences, buffers, and enzymes) was around <span class="highlight">$1.45</span>,  without the hardware (as determined on our <a class="hyperlink" href="https://2020.igem.org/Team:Leiden/Proof_Of_Concept">Proof of Concept</a> page). If the kit is <span class="highlight">mass-produced</span>, this price can be lowered even further.
+                                            </p>
+                                            <p>
+                                                Our team felt that the cost of a kit should not limit the access to diagnostic devices. We therefore plan to implement a self-sustaining hybrid <span class="highlight">economic system</span> to make our kits affordable. In this hybrid model, the price of the tests would depend on the income of the countries. High income countries, would then pay a "premium" price that would <span class="highlight">co-fund</span> the purchase of tests by NGOs or governments in lower income countries.
+                                            </p>
+                                        </div>
+                                    </div>
+                                </div>
+                            </div>
+                            <div id="slide1-chapter6" class="popout">
+                                <div title="Click to read more" id="coll6" role="button" tabindex="0"class="collapsible main-nav-link" linkedidchapter="slide1-chapter6">
+                                    Logistics & Regulation
+                                </div>
+                                <div class="collapsible-content">
+                                    <div class="collapsible-content-wrapper">
+                                        <h3>Question: How can kits reach our kits reach the target population? How can they be distributed accordingly?  </h3>
+                                    </div>
+                                    <div class="content-wrap">
+                                        <div class="question-hp">
+                                            <h2 > Input</h2>
+                                            <div class="question-content">
+                                                <p>
+                                                    <em>It is probably rather easy for an inhabitant of high-income countries to get tested for a particular disease. However, for certain regions, it can be a true challenge to reach a target population<a class="hyperlink main-nav-link" linkedidchapter="slide1-chapter9"><sup>9</sup></a>. Therefore, our team has asked experts which challenge should be overcome to reach the populations that can benefit most from our development. This entails research on regulations but also some logistical aspects of distribution.  </em>
+                                                </p>
+                                            </div>
+                                            <div class="question-content">
+                                                <h3>Regulations</h3>
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/4/49/T--Leiden--Qserve.png" alt="Picture of Qserve">
+                                                </div>
+                                                <div >
+                                                    <h4> Qserve  </h4>
+                                                    <p>Qserve is a consultant company that helps diagnostic companies to get a CE label from the notified bodies. There are two notified bodies in the Netherlands, Dekra inc. and BSI. A CE label is proof that a product conforms to the European regulation and is therefore essential when bringing a product to the European market. The EU regulation our kit needs to abide by, in order to obtain the CE marking, is the In Vitro Diagnostic Regulation 2017/746. The notified bodies test our kit independently to ensure that our kit abides by the regulation.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/b/b5/T--Leiden--VanVugt.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Erik van Vught, Goffin Molecular Technologies </h4>
+                                                    <p>
+                                                        When trying to receive approval to sell our kit overseas, Mr van Vught suggested to first market the product in our own country, the Netherlands, as it is one of the leading countries in (molecular) diagnostics, therefore also the most critical market. If it works in the Netherlands, we would be more comfortable selling it in other countries.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/f/f5/T--Leiden--Rene_Paulussen.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>René Paulussen, managing director Mondial Diagnostics</h4>
+                                                    <p>
+                                                        Outsourcing or licensing a part of our business to large companies is the optimal for bringing our kit on a foreign market as they have a great sales and distribution network and often have contacts with regulatory bodies or government members. The latter is important as good relations with the local government facilitates the approval and implementation of the devices.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/b/ba/T--Leiden--Ward_Heij.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Ward Heij, Monitor Deloitte</h4>
+                                                    <p>
+                                                        Ward Heij told us that there is a difference between public and private markets. Procurement for public healthcare is often centralized either on a national or regional level. Sometimes, smaller consortia of hospitals procure together. It is rare that individual hospitals procure for themselves. Additionally, procurement is often done through tendering.
+It is also important to remember that due to price competition, better quality is not necessarily sought after. Often, the cheapest product that matches all certifications is sold.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/c/c4/T--Leiden--Guus_Eskens-min.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Guus Eskens, Retired researcher and CEO of CARE Nederland </h4>
+                                                    <p>
+                                                        Guus shared with us some of his extensive experience with CARE Netherlands, Cordaid, IDA Foundation, and years of living in Africa. He provided us with insight into the state of the market for diagnostics and therapeutics in Africa. In certain countries, the major players in the medical field are international NGOs, often financed by large funds or wealthier countries. These NGOs work with funding programs (or missions), where they address a single crisis situation. The equipment and drugs are purchased depending on the goods that have been certified, tested, and approved by large bodies such as the FDA and the WHO. The equipment is then imported into the area in need. In a crisis situation, the complicated and delocalized logistics, may cause an inevitable administrative delay in bringing a novel product from the lab to the field. Therefore, to get into this market, the kits have to be approved by the larger bodies. The idea of modularity is interesting, but it will never be approved by these bodies if the tests are modular. As a consequence, the immediate, "rapid response" to epidemics is not fully achievable.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <h3> Distribution/Logistics</h3>
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/f/f5/T--Leiden--Rene_Paulussen.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>René Paulussen, managing director Mondial Diagnostics</h4>
+                                                    <p>
+                                                        According to Mr. Paulussen, distribution is always a challenge. However, the difficulty lies in getting our kit approved in the countries where we want to sell. Once we get our approval first, then the distributors will come.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/2/24/T--Leiden--Otto_Kroesen.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Dr Otto Kroesen, researcher of cross-cultural entrepreneurship for development</h4>
+                                                    <p>
+                                                        Dr. Kroesen also proposed that (a part of) the production could be done in Africa. He gave South Africa as an example to do packaging in. However, it is definitely important to take into account what the benefits are of moving production to Africa.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/f/f5/T--Leiden--Rene_Paulussen.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>René Paulussen, managing director Mondial Diagnostics</h4>
+                                                    <p>
+                                                        Distribution in Sub-Saharan Africa happens on trucks driving through the desert. The temperature inside these trucks can exceed 55°C. Therefore, it is essential that the kits are robust and can withstand these extreme temperatures.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/a/a2/T--Leiden--Heleen_Koudijs.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Dr Heleen Koudijs, Tropical doctor</h4>
+                                                    <p>
+                                                        Dr Koudijs told us that in Ethiopia RDTs are distributed in distribution centers (mostly from UNICEF) on scooters on walking paths to the remote villages.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/6/60/T--Leiden--John_Tonkinson.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>John Tonkinson, DCN Dx</h4>
+                                                    <p>
+                                                        Mr. Tonkinson suggested making a kit with the least plastic possible, small and compact, which would be easier for transport.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/c/c4/T--Leiden--Guus_Eskens-min.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Guus Eskens, Retired researcher and CEO CARE Nederland</h4>
+                                                    <p>
+                                                        Mr. Eskens told us that the conditions for logistics and distribution in certain remote places, like on the African continent, can vary greatly. These variations can complicate the distribution in certain regions. The availability and reliability of electricity can compromise the cold transport chain and the very long distances between regions yield high distribution costs. The temperature in containers left in harbors without a cooling system can reach 60-70°C. Their unreliability can be a problem to safeguard the quality of the tests.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                        </div>
+                                        <div class="integration-hp">
+                                            <h2> Integration</h2>
+                                            <h3> Regulations</h3>
+                                            <p>
+                                                Understanding the <span class="highlight">regulations</span> that govern the market of diagnostic devices globally is important. Experts helped us understand what it takes to bring a kit to a market where the standards are extremely high, versus a market where low(er) cost applications are often the norm.
+                                            </p>
+                                            <p>
+                                                Indeed, in high-income countries, the <span class="highlight">governments</span> make up stocks of basic medical necessities. Therefore, the products  have to be tested and approved by the notified bodies (such as the CE marking). In contrast, in lower income countries, large <span class="highlight">NGOs</span> fund these medical supplies and are funded by foundations. They purchase these based on <span class="highlight">recommendations</span> from bodies like the WHO. Therefore, kits first have to be tested and approved and gain a reputation on the market. However, there is a risk that modular kits might not reach the target users as quickly as initially intended due to inevitable administrative <span class="highlight">delay.</span> Yet the nature of our kit (pre-produced generic part) could help in reducing this delay in an epidemic setting.
+                                            </p>
+                                            <p>From a business perspective, it is complicated to market and <span class="highlight">commercialize</span> a modular kit that cannot be tested immediately. Therefore, our team has become aware that we have to start small and gradually build up the product to its final, modular application. By focussing on the group of respiratory-borne RNA viruses, our kit could already be applied and tested for <span class="highlight">specific diseases</span> like influenza. If we prove that the kits respond to the requirements for specific diseases (sensitivity, accuracy, speed), it can increase the credibility of our modular application, build up a <span class="highlight">reputation</span> and accelerate their approval and implementation in a crisis situation.
+                                            </p>
+                                            <h3> Distribution/Logistics</h3>
+                                            <p>
+                                                In lower-income countries, including many countries on the African continent, transport and logistics are often difficult for complex, bulky, fragile, refrigerated medical devices. Therefore, <span class="highlight">robustness</span> and temperature insensitivity are the qualities sought after in a kit. Additionally, the distribution costs in more isolated regions can be very elevated. As a consequence, the regions where these kits are highly needed are eventually poorly covered in the required medical supplies.
+                                            </p>
+                                            <p>
+                                                The majority of the reagents in the Rapidemic test kits can be <span class="highlight">freeze-dried</span>, which can respond to the need for better conservation and subsequent <span class="highlight">long-term storage</span> and distribution of the products. We predict that this could also render the reagents more resistant to high temperatures<a class="hyperlink main-nav-link" linkedidchapter="slide1-chapter9"><sup>10</sup></a>. Additionally, as we are aiming to design the embedding of the test reagents in a simple, robust device, this will likely require less specialized distribution systems.
+                                            </p>
+                                            <p>
+                                                The exact <span class="highlight">hardware</span> of the kits has not yet been detemined. However, given that very little volume of the reagents is necessary, the kits could be made in a very <span class="highlight">compact</span> format. Our team has even considered doing a <span class="highlight">paper-based</span> test. This  will also facilitiate the distribution of the tests.
+                                            </p>
+                                        </div>
+                                    </div>
+                                </div>
+                            </div>
+                            <div id="slide1-chapter7" class="popout">
+                                <div title="Click to read more" id="coll7" role="button" tabindex="0"class="collapsible main-nav-link" linkedidchapter="slide1-chapter7">
+                                    Disposal
+                                </div>
+                                <div class="collapsible-content">
+                                    <div class="collapsible-content-wrapper">
+                                        <h3>Question: How can we make ensure that our kit is disposed of in a safely manner?  </h3>
+                                    </div>
+                                    <div class="content-wrap">
+                                        <div class="question-hp">
+                                            <h2 > Input</h2>
+                                            <div class="question-content">
+                                                <p>
+                                                    <em>As mentioned in "Users and user friendliness", the best way to make sure that the kit is properly disposed of is by entrusting trained professionals with the use of the kit. In the Netherlands, the hospitals are responsible for managing their own waste. How can we ensure that the used kits present no environmental or health risk whatsoever, in the Netherlands and abroad? Which waste category would used kits qualify as?  </em>
+                                                </p>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-wrapper-stay-flex-no-space">
+                                                    <div class="figure-container width40-no-margin">
+                                                        <img src="https://static.igem.org/mediawiki/2020/3/30/T--Leiden--Armand_Paauw.png" alt="Picture of this person">
+                                                    </div>
+                                                    <div class="figure-container width40-no-margin">
+                                                        <img src="https://static.igem.org/mediawiki/2020/e/ec/T--Leiden--Hans_van_Leeuwen.png" alt="Picture of this person">
+                                                    </div>
+                                                </div>
+                                                <div >
+                                                    <h4> Dr Armand Paauw, Scientist at TNO Defence, Security and Safety, & Dr Hans van Leeuwen, Senior Scientist at TNO </h4>
+                                                    <p>According to the two scientists, our kit should be considered as contaminated hospital waste and should be disposed of accordingly. They also said that in order to inactivate the pathogens, the samples should be lysed entirely, which would render the pathogens harmless. This can be achieved with a lysis buffer, for instance. However, they suggested testing whether the pathogens are effectively neutralized and that a lysisbuffer is sufficient to do so. Alternatively, they told us that the samples could be inactivated by steaming them for 10 minutes at 80°C before disposal.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <h3>
+                                                    Waste transporting company
+                                                </h3>
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/f/f9/T--Leiden--Bram_de_graaf.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Bram de Graaf, Project Manager hazardous waste NNRD </h4>
+                                                    <p>
+                                                        The NNRD is a waste transporting company responsible for the waste collection and transport for the areas Drachten and Groningen. All the waste transporting companies in the Netherlands follow the regulations from the ADR. The driver has to have an ADR diploma and the truck has to be ADR certified as well. After the waste is collected from the hospitals, the waste is dropped brought to the depot until there is enough waste to be transported to the waste disposal company Zavin in Dordrecht.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <h3>Waste disposal company </h3>
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/2/2f/T--Leiden--Ron_Roffel.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Ron Roffel, Operational director Zavin  </h4>
+                                                    <p>
+                                                        According to Mr. Roffel, the hospital staff in the Netherlands is rather considerate of waste separation and disposal infrastructure. However, he said that  Dutch general practitioners sometimes fail to separate their medical waste correctly, yet this is improving. According to Mr. Roffel, if the waste disposal of point-of-care kits is left to the general public (patients), proper separation of the medical waste is practically unachievable.
+                                                    </p>
+                                                    <p>
+                                                        We also learned from this visit that the majority of medical waste worldwide is improperly disposed of, even in Europe. In a best-case scenario, all the medical waste is incinerated in the open air. In worse conditions, the kit may end up in an open landfill or in nature. In the latter case, the kit should be hermetically sealed off and non-hazardous, to ensure it does not present a health threat to the population.
+                                                    </p>
+                                                    <p>
+                                                        To read more about our visit to Zavin: <a onclick="showDivs(1)" class="hyperlink">Click here!</a>
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                               <h3> The future of waste diposal</h3>
+                                               <div class="figure-container width40-no-margin">
+                                                <img src="https://static.igem.org/mediawiki/2020/6/66/T--Leiden--Gerard_Vincent.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Gerard Vincent, CEO Red Bag Solutions Europe</h4>
+                                                    <p>
+                                                        Red bag solutions is an alternative option for medical waste disposal in the Netherlands. Instead of incineration, they use water sterilization. The benefits of their technique are mainly environmental. They can reuse up to 95% of all their materials. This tech also saves up almost 100% of nitrogen and 75% of CO2 from medical waste.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <h3> Waste disposal in Africa and Asia</h3>
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/a/a2/T--Leiden--Heleen_Koudijs.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Dr Heleen Koudijs, Tropical doctor </h4>
+                                                    <p>
+                                                        According to Dr. Koudijs, the waste in Ethiopia is thrown on top of a pile until the pile is big enough to be incinerated out in the open. However, the situation in hospitals is better. Hazardous waste in hospitals in Ethiopia is well separated. It is very unclear how the waste is separated and processed in countries like Zambia and Tanzania.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/c/c1/T--Leiden--Permata.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Dr Assica Permata, M.D. currently working on TB in a research environment</h4>
+                                                    <p>
+                                                        Dr. Permata shared with us how infectious waste is handled in Indonesia. One of the anecdotes that stuck with us is the fact that some doctors expose contaminated material to sunlight for sterilization. The remaining waste is disposed of in bags and likely burned.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                        </div>
+                                        <div class="integration-hp">
+                                            <h2> Integration</h2>
+                                            <p>
+                                                Through contact with the diagnostic companies, we have rapidly understood that RDT developers do not integrate the <span class="highlight">end-of-life considerations</span>, such as environmental or (health) safety, into the developmental stages of the products. We also realized that developing a medical product for low-resource countries with inadequate infrastructure can present certain <span class="highlight">risks</span>, that should be taken into account in the design process. Therefore, we contacted professionals in the field to understand how our team could consider and integrate these considerations into our project, even at a very early stage.
+                                            </p>
+                                            <p>
+                                                After our kit has been used, it will be classified as hospital waste and should therefore be treated as such. In the Netherlands, the quality of the <span class="highlight">disposal systems</span> in place is not perfect, yet the country is among the best in the world. Just a few countries further, the quality of the waste treatment is drastically worse or even non-existent<a class="hyperlink main-nav-link" linkedidchapter="slide1-chapter9"><sup>11</sup></a>. Often, the disposed medical waste is mixed with regular house waste and landfilled, or incinerated without post-treatment of the fumes.
+                                            </p>
+                                            <p>When kits are properly <span class="highlight">incinerated</span>, there is less environmental value in making our test kits from degradable material (with harmless contents), such as biodegradable plastics. One way to further decrease the impact of the kits would be to use recycled content to reduce the unnecessary incineration of virgin material. However, opting for recycled materials sometimes also entails decreased polymer quality and therefore reduced robustness. This may affect the choice of material since it is important that the <span class="highlight">quality</span> and <span class="highlight">robustness</span> of the kits are maintained. Additionally, if the kits are incinerated, all potentially infectious material is killed.
+                                            </p>
+                                            <p>
+                                               Instead, if the hospital waste is <span class="highlight">placed in a landfill</span> to which the population has access, the content of the kits could present a risk. Therefore, the potentially infectious material should be <span class="highlight">lysed</span>. The use of biodegradable materials could decrease the environmental impact of the kits in these circumstances.
+                                            </p>
+                                        </div>
+                                    </div>
+                                </div>
+                            </div>
+                            <div id="slide1-chapter8" class="popout">
+                                <div title="Click to read more" id="coll8" role="button" tabindex="0" class="collapsible main-nav-link" linkedidchapter="slide1-chapter8">
+                                    Ethics
+                                </div>
+                                <div class="collapsible-content">
+                                    <div class="collapsible-content-wrapper">
+                                        <h3>Question: What social considerations do we need to take into account when doing business in different areas of the world?   </h3>
+                                    </div>
+                                    <div class="content-wrap">
+                                        <div class="question-hp">
+                                            <h2 > Input</h2>
+                                            <div class="question-content">
+                                                <p>
+                                                    <em>Doing business in Africa is certainly not the same as doing business in Europe. Topics like culture, social taboos, trust and extreme poverty all play a significant role in determining if our product is going to be a success or a failure.  </em>
+                                                </p>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/a/a2/T--Leiden--Heleen_Koudijs.png" alt="Picture of this person">
+                                                </div>
+                                                <div >
+                                                    <h4>Dr Heleen Koudijs, Tropical doctor</h4>
+                                                    <p>A significant portion of the Ethiopian population lives in extreme poverty. This means many people in Ethiopia earn less than one euro per day. Therefore, taking a day off to test has severe consequences for the families. Testing in Ethiopia is regulated and performed by the Ethiopian government. The patients are tested and then put into isolation (quarantine) until the results are in. If the result of the test is positive then they are isolated two more weeks, if not then they are free to go. This has severe financial consequences for the families involved. Another cultural consideration is that Ethiopians will probably not wait long to get the test result. According to Dr Koudijs, keeping people in hospitals was, therefore, quite the issue. To combat this, it is recommended to have a kit that has a test result within two hours. Lastly, having a disease (like HIV, for instance) in countries like Kenia is a big social taboo. Privacy is therefore crucial and should not be neglected.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                            <div class="question-content">
+                                                <div class="figure-container width40-no-margin">
+                                                    <img src="https://static.igem.org/mediawiki/2020/2/24/T--Leiden--Otto_Kroesen.png" alt="Picture of this person">
+                                                </div>
+                                                <div>
+                                                    <h4>Dr Otto Kroesen, researcher in cross-cultural entrepreneurship for development </h4>
+                                                    <p>
+                                                        According to Dr. Kroesen, there is very little trust in shop owners. Even physicians are not always trusted. If the kits are given to health workers for free then there is a good chance that kits will go missing. However, for any transaction, it is important to have the trust of the locals. It is also important to have kits handled by trustworthy people. Trust can be earned through schools and churches. However, it does take a lot of time to gain trust.
+                                                    </p>
+                                                </div>
+                                            </div>
+                                        </div>
+                                        <div class="integration-hp">
+                                            <h2> Integration</h2>
+                                            <p>
+                                                Social considerations should not be forgotten when trying to enter the African market. Gaining <span class="highlight">trust</span> is of vital importance. The best strategy regarding the quickest entry into the market is <span class="highlight">licensing</span> our product to a company with a good reputation and which is trusted by the local population. The social considerations regarding the feeling of being looked down upon and the social taboo related to a disease (like HIV) are struggles that are mainly affecting the physicians. Therefore, these issues cannot be solved by an RDT since these issues are <span class="highlight">cultural</span>. The fact that people are not willing to wait is problematic. Fortunately, this issue can be (partially) solved by having shorter (less than 2 hours) <span class="highlight">reaction times</span>.
+                                            </p>
+                                        </div>
+                                    </div>
+                                </div>
+                            </div>
+                            <div class="next-chapter">
+                                <div class="next-buttons">
+                                    <a onclick="plusDivs(1)" href="#marker" class="single-button">
+                                        <div class="button-content-wrapper">
+                                         A day at Zavin
+                                        <i class=" fas fa-caret-right"></i>
+                                        </div>
+                                    </a>
+                                </div>
+                            </div>
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      <main style="margin-top:2rem;" class="overall-1">

Difference between revisions of "Team:NCKU Tainan/Human Practices"

Revision as of 13:41, 20 July 2021

Human Practices

Question: Which challenge is iGEM Leiden 2020 going to take on?

Input

World Health Organization

McNerney, R. (2015). Diagnostics for developing countries. Diagnostics, 5(2), 200-2094.

Dr Assica Permata, M.D. currently working on TB in a research environment

Peeling & Mabey, 20105.

Robin van Houdt, microbiologist at the Dutch Association for Medical Microbiology and the UMC Amsterdam

Huram Konjen, Chief executive officer of Dianox

Integration

Question: Developing a rapid diagnostic test for infectious diseases: where do we start?

Input

Niek Savelkoul, iGEM 2017 Wageningen Mantis & Founder of Scope Biosciences

Prof. dr. Janneke van de Wijgert, professor in epidemiology UMC Utrecht & Liverpool

Dr Peter Bredenbeek, assistant professor in Virology LUMC

Thomas Caltagirone, CEO of Alpagen LLP

Dr Armand Paauw, Scientist at TNO Defence, Security and Safety, & Dr Hans van Leeuwen, Senior Scientist at TNO

iGEM EPFL 2019 ViTest

Integration

Question: How can we identify a niche in the vast and complex field of infectious diseases?

Input

Dr Peter Bredenbeek, assistant professor in Virology LUMC

René Paulussen, managing director Mondial Diagnostics

Dr Lieselotte Hardy, Doctor at Institute of Tropical Medicine Antwerp, Belgium

Dr Heleen Koudijs, Tropical doctor

Mosquito-born diseases

Dr Heleen Koudijs, Tropical doctor

Dengue and Malaria patients

Hélène van Oorschot, Student in medicine

Disease X and Epidemic preparedness

Professor Pim Martens, Maastricht Sustainability Institute, director of the International Centre for Integrated assessment and Sustainable development (ICIS), School of Business and Economics, founder of AnimalWise and member of House of Animals, member of Dutch Health Council

Dr Armand Paauw, Scientist at TNO Defence, Security and Safety, & Dr Hans van Leeuwen, Senior Scientist at TNO

Willem Mees van der Bijl, Director IDE Netherlands at IDE Group

Integration

Timeline

Questions: Who is going to use our kit? Where is our kit going to be used?

Input

Dr Sophie van Baalen, Researcher team medical technology for Rathenau institute

Patients: Malaria, TB, Dengue and SARS-CoV-2

René Paulussen, managing director Mondial Diagnostics

Dr Heleen Koudijs, Tropical doctor

Eric de Coster, Medical coördinator in the General Infectious Disease Control and Travel Advice

How can we then ensure that our kit is userfriendly?

Dr Heleen Koudijs, Tropical doctor

John Tonkinson, Chief Business Development Officer DCN Dx

René Paulussen, managing director Mondial Diagnostics

Professor dr Aldrik Velders, Nanobiotechnology at Wageningen University & Dr Vittorio Saggiomo, Organic Chemistry

Integration

Timeline

Question: How can we ensure that the cost of a test does not compromise the accessibility to all?

Input

Niek Savelkoul, iGEM 2017 Wageningen Mantis & Founder of Scope Biosciences

Prof. dr. Janneke van de Wijgert, professor in epidemiology UMC Utrecht & Liverpool

John Tonkinson, Chief Business Development Officer DCN Dx

Erik van Vught, Goffin Molecular Technologies

Dr Dam, Medical doctor

Dr Heleen Koudijs, Tropical doctor

Dr Sophie van Baalen, Researcher team medical technology for Rathenau institute

Integration

Question: How can kits reach our kits reach the target population? How can they be distributed accordingly?

Input

Regulations

Qserve

Erik van Vught, Goffin Molecular Technologies

René Paulussen, managing director Mondial Diagnostics

Ward Heij, Monitor Deloitte

Guus Eskens, Retired researcher and CEO of CARE Nederland

Distribution/Logistics

René Paulussen, managing director Mondial Diagnostics

Dr Otto Kroesen, researcher of cross-cultural entrepreneurship for development

René Paulussen, managing director Mondial Diagnostics

Dr Heleen Koudijs, Tropical doctor

John Tonkinson, DCN Dx

Guus Eskens, Retired researcher and CEO CARE Nederland

Integration

Regulations

Distribution/Logistics

Question: How can we make ensure that our kit is disposed of in a safely manner?

McNerney, R. (2015). Diagnostics for developing countries. Diagnostics, 5(2), 200-209⁴.

Peeling & Mabey, 2010⁵.