1.Background of the project
Colorectal cancer (CRC) is a common digestive tract malignant tumor worldwide. It has high incidence rate and mortality. It is the third most common cancer in the world, which seriously threatens human life and health[1][2][3].According to the global cancer epidemic Statistics (GLOBOCAN 2020) released by the international cancer research agency of the World Health Organization, it is estimated that in 2020, there will be 1931600 new cases and 935200 deaths of colorectal cancer in the world, accounting for 10.0% and 9.4% of the total cancer incidence and deaths respectively. The number of new cases and deaths will rank third and second among all malignant tumors respectively[4].According to the data of the World Health Organization (WHO), it is expected that by 2030, the number of patients with colorectal cancer will increase by 77% and the number of deaths will increase by 80%[5][6].
Colorectal cancer is not only a high incidence rate and mortality rate, but a recent study published in JAMA Netw Open indicates that the survival rate of patients with early colorectal cancer is lower. At the same time, the researchers further evaluated the heterogeneity of CRC patients and found that the survival advantage was the greatest among individuals diagnosed between 35 and 39 years old, but this higher survival rate was limited to stage I and II. Therefore, early prediction of colorectal cancer is very important to reduce the overall mortality.
So what are the diagnosis and treatment methods of colorectal cancer on the market at this stage?
Enteroscopy - traditional endoscopy is widely used in clinic. The diagnostic results of pathological specimens obtained by this method are regarded as the gold standard for the early diagnosis of colorectal cancer[7].However, as an invasive examination method, it has the risk of perforation and bleeding, which may cause intestinal damage and related complications, and the population compliance is low[8].Besides, the pain of colonoscopy is high, and the patients are prone to conflict, which is not conducive to the prediction of large-scale colorectal cancer.
CT - CT virtual colonoscopy can be viewed at any position and angle of view in the reconstructed colon cavity. The examination time is short and the subject has high tolerance. However, a meta-analysis of CT virtual colonoscopy in colorectal cancer screening shows that virtual colonoscopy has greater advantages over traditional endoscopy for lesions with diameter ≥ 6mm, but it is difficult to detect smaller lesions[9].In addition, CT virtual colonoscopy has the risk of X-ray radiation[10].In addition, adequate bowel preparation is also required before operation. In the face of poor bowel preparation, the missed diagnosis rate of colorectal cancer will also increase significantly.
Fecal occult blood test paper - this method is non-invasive, simple and convenient. However, this method has poor specificity and sensitivity, and can not detect the presence of early benign polyps. The necessary condition for the detection of fecal occult blood is that the tumor is accompanied by bleeding, and the tumor without bleeding can be missed.
In summary, all kinds of detection methods now have their own advantages and disadvantages. Considering all kinds of schemes, none of them can meet all comprehensive needs of simple, convenient, high precision and low cost. This means that a new CRC detection method needs to be developed to fill the market vacancy.Our colorectal cancer prediction project is consistent with such requirements in the biological module, hardware and software module.
2. Project introduction and product positioning
1) Project introduction
Our project has developed an ultra-sensitive miRNA detection method based on loop-mediated isothermal amplification (LAMP) and CRISPR-Cas12a trans cleavage technology. The technical route and operation method of early screening for colorectal cancer constructed for the integrated project, to overcome the complex process of traditional detection methods, low patient tolerance, unsuitable for large-scale early screening, etc. The project built a colorectal cancer early screening platform in order to realize the fast, portable and easy-to-operate "sample-to-answer" integrated detection of colorectal cancer, it provides effective intelligent interactive IVD equipment for large-scale early screening. After testing, the system is easy to operate, the process is completed within 1h, and the sensitivity can reach fM level. In addition, our equipment also has the ability to detect different miRNAs, making it possible to build a standardized cancer detection platform.

Equipment use process

Equipment modeling diagram

Equipment internal structure

For detailed modules such as the principle of the project, you can move to our project module for a more detailed understanding.
2) Product positioning
Our product advantages are mainly positioned to create a cancer early screening platform that integrates convenient and simple operation, high-sensitivity detection, high-throughput standardization, and extended information openness.
①Portable and integrative platform of cancer early screening with simple operation
The device of our project has the characteristics of miniaturization, portability and simple operation, the biometric process can be carried out step by step via a machine-driven slip chip without much user involvement. It bases on the development of software interactive page to give users the corresponding operation tips and simplifies the complicated manual operation process in the detection process by the integrated hardware design. Therefore, the detection platform developed by the project is based on the public and does not require the operation of professional technicians, which provides the possibility of large-scale early screening.
②Practical platform of cancer early screening with high sensitivity
Our project combines the advantages of CRISPR/Cas12 technology for specific recognition and cutting and the advantages of LAMP technology for the signal of nucleic acid amplification that CRISPR/Cas12 system is highly specific when applied in nucleic acid detection. LAMP technology can perform exponential amplification of target nucleic acid in a short time and improve detection sensitivity. It is this combination of technologies that enables our project to achieve the high sensitivity detection target of fM level.
③ Standardized platform of cancer early screening with high-throughput
The project builds a corresponding integrated detection platform for early screening of miRNA biomarkers for colorectal cancer and integrates the detection of multiple miRNAs on a slip chip to achieve high-throughput detection system design. In the future, the project can further expand the ability to detect biomarkers and detect multiple cancers, providing corresponding hardware support strategies for the construction of standardized cancer detection platform.
④ Opening platform of cancer early screening with extending information
With the continuous development of information technology such as 5G, internet of things and cloud services, the detection equipment with smart phones as the detection port and data transmission starting point will have great significance. The visualization of the processes and results by using WeChat mini programs on smartphones is greatly suitable for end-user experience.
3)Target users
Our audience groups can focus on students and office workers who regularly carry out organizational physical examination, and also serve relevant personnel of all ages who need the project. It can also be carried out for hospital examination to help the auxiliary diagnosis and treatment of patients with clinical colorectal intolerance.
At present, colonoscopy and fecal occult blood are commonly used in clinical screening, but their applications are mainly concentrated in the middle and late stage of cancer. There are also problems such as low sensitivity, high clinical cost, and causing various complications or body damage, which make the current early screening methods of colorectal cancer with high clinical popularity have certain limitations. Therefore, according to the needs of early screening, the project integrates CRISPR / CAS technology and lamp amplification technology to realize the rapid detection of colorectal cancer related miRNA under constant temperature, and develops a colorectal cancer assisted early screening system with the characteristics of fast, simple, economic, safe, good sensitivity and high throughput, supporting the miniaturization, lightweight, easy to carry, mobile phone based The easy-to-use mobile phone instruments and equipment can assist in screening patients with early colorectal cancer among healthy people, and can also help in the auxiliary diagnosis and treatment of patients with clinical colorectal endoscopy intolerance, so as to find more possibilities for the methodological construction of early colorectal cancer screening, and provide a new strategy for the construction of standardized cancer detection platform.
3.Project feasibility analysis
Market status - macro environment PEST analysis
P (political - macro political environment analysis)
For the implementation of the project - in terms of supporting college students' innovation and entrepreneurship, the national government has given a lot of preferential policies to college graduates in tax, financial support, training, entrepreneurship services and so on. For example, tax preference, entrepreneurship guarantee loans and interest discount support, exemption from relevant administrative fees, training subsidies, free entrepreneurship services, etc.
E (economic macroeconomic environment analysis)
After the impact of COVID-19, based on the recent national economic operation in the first quarter of 2021 released by the National Bureau of statistics, China's first quarter 2021 macroeconomic data was released, showing a steady start and stable recovery, laying the foundation for achieving the annual economic growth target. Residents have fully begun to enter a normal life, and the consumption level is further increasing.
In such a relatively stable economic environment, the implementation and development of new projects are easier to achieve; It is expected that the project products will be more easily noticed and accepted when they are put into market.
Industry competition analysis
With the improvement of people's knowledge level and increasing attention to health. Colorectal cancer has begun to come into public view. Many detection projects for colorectal cancer are emerging. In this iGEM competition, there is more than one team for colorectal cancer prediction. So what are the advantages of our project?
1) Operational advantages.
One of our project ideas is POCT to achieve large-scale convenience prediction. Our hardware and software provide a good foundation for the biological detection module. Through our convenient device for detection, the data will be synchronized to our wechat applet in real time, so as to avoid the cumbersome operation of traditional methods and high requirements for professionals.
2) Specific advantage
Because most miRNAs can regulate protein synthesis at the post transcriptional level, they are almost involved in all aspects of regulating cell activities. MiRNA is involved in the regulation of PI3K / Akt, NF KB, MAPK, JAK / STAT3 and other tumor related signal pathways. It belongs to a broad-spectrum marker[11]. Therefore, miRNA is often used as a detection or potential diagnostic marker of a variety of tumors, with abnormal expression and poor specificity in a variety of tumors. In this project, three miRNAs with strong specificity and correlation were selected for data mining through TCGA database, and the specificity was evaluated. Finally, the joint detection of three miRNAs was adopted, which greatly improved the detection specificity.
3) Service advantage
From the perspective of patients, the project considers the feelings of patients in many aspects, so as to avoid invasive detection, avoid secondary trauma and so on, better protect the privacy of patients in many aspects and take care of their psychological feelings.
4.Security and Challenges
1. safety form
Our project has completed basic operations in the laboratory and verified its success. And from the safety form, it can be seen that our project can be completed safely in the laboratory, and there are also safety guarantees implemented in the market.

2. Project implementation risk prevention and measures
1) At the technical level, due to the rapid development of science and technology, synthetic biology is booming, and the upgrading of every technology is very rapid. In order to make our equipment better serve the public. We must establish our own technical advantages, ensure that functions keep pace with the times, collect feedback information in time and make improvements.
2) In terms of policies, as start-ups, you may be troubled by funding problems, but the state and schools currently have relevant loan support policies for start-ups. In the case of fully integrating the advantages of the start-up plan, this should not be too much. Worry.
3) In terms of management, our project focuses on large-scale colorectal cancer prediction, so it is very important to grasp the overall situation and information. After the implementation of the project, we need to fully communicate with partners to quickly understand the overall situation of users. So as to better improve our project and operation.
4) In terms of capital, as college students' innovation and entrepreneurship, they still lack certain professional basic knowledge of capital management and so on. Therefore, a reasonable plan for the use of funds to improve technical capabilities while reducing operating costs requires our team to actively learn and ask relevant people for advice.
5) In terms of project implementation, during this competition, we have completed the 1.0 version of the project. In the follow-up, we need to continue to optimize the project-find relevant professionals to provide suggestions, and combine related improvements to produce version 2.0. After that, we will look for related equipment companies and related practice hospitals for product production and market launch. After a certain period of time, we will collect feedback information from WeChat clients, hospitals and companies, and improve our equipment based on this, and finally put it into use on a large scale.
[1] WANG F,CHEN ZN,ZHANG YX. Effects of PCDH10 gene overexpression on proliferation and migration of color- ectal cancer cells[J]. Journal of Zhengzhou University ( Medical Sciences) ,2020,55( 5) : 653
[2] Marley A R,Nan H. Epidemiology of colorectal cancer [J]. International Journal of Molecular Epidemiology and Genetics,2016,7( 3) : 105 - 114.
[3] Kolligs F T. Diagnostics and epidemiology of colorectal cancer[J]. Visceral Medicine,2016,32( 3) : 158 - 164.
[4] WHO. Global Health Estimates 2020: Deaths by Cause, Age, Sex, by Country and by Region, 2000-2019[Z/OL]. [2021-02-20].
[5] IARC. The Section of Cancer Surveillance[Z/OL]. [2021-02-20].
[6] BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6):394-424.
[7] McComiskey DA,Barrett B,Flemming J,et al. Colorectal Cancer Outcomes in a Large Negative Computed Tomography Colonography Screening Cohort[J]. Can Assoc Radiol J,2019,70( 4) : 452-456.
[8] Burt RW, Barthel JS, Dunn KB, et al. NCCN clinical practice guidelines in oncology. Colorectal cancer screening [J]. J Natl Compr Canc Netw, 2010,8(1):8-61.
[9] Blachar A,Levy G,Graif M,et al. Computed tomography colonog- raphy ( " virtual colonoscopy" ) in Israel: Results of the National CT Colonography Survey of the Israeli Association of Abdominal Imaging and the Israeli Radiological Association[J]. Isr Med Assoc J,2008,10( 10) : 707-712.
[10] Xu Sijia, Zhang Xieyi, Huang Gang, et al. Research progress in imaging diagnosis of colorectal cancer [ J ]. Journal of Shanghai Jiaotong University (Medical Edition), 2016, 36 (1): 124-127
[11] Liu Baorui, Xie Li. MiRNA: a new generation of tumor biomarkers [J]. Journal of Clinical Oncology, 2010, 15 (1): 1-5