Team:TUDelft

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The Global Hidden Hunger Crisis

To date, an estimated two billion people worldwide suffer from hidden hunger, also known as micronutrient deficiencies [1]. Hidden hunger is defined as a lack of vitamins and minerals and is most prevalent in sub-Saharan Africa and South Asia [2]. The consequences of hidden hunger are various health issues, often exhibiting generic symptoms, making it difficult to diagnose. Long-term and acute deficiencies can result in severe health issues, such as growth impairment and increased risks of infectious diseases [3]. Moreover, micronutrient deficiencies may contribute to socioeconomic gaps within populations [4]. Intervention with non-specific micronutrient supplements has shown to be inefficient. Nevertheless, data-tailored intervention programs can contribute to tackling hidden hunger [1].

Diagnostic Accessibility Withholds Exposure of Hidden Hunger

Non-governmental and governmental organizations have taken actions to tackle hidden hunger. However, progress is slow and unequally distributed across different regions and countries due to insufficient data on micronutrient deficiencies. This data is needed for developing an effective strategy. The bottleneck remains in the accessibility of the current diagnostic tests, such as high-performance liquid chromatography and mass spectrometry, in countries with insufficient economic and logistical means [1, 5, 6].

How Will AptaVita Tackle Hidden Hunger?

Our goal is to develop AptaVita: an accessible, quantitative, and modular rapid diagnostic test for vitamin deficiencies to accelerate the obtention of prevalence data, exposing hidden hunger and making it addressable. The technology uses a novel and modular aptazyme-based biosensor and dedicated hardware for a quantitative read-out.

Aptazyme and reporter gene
Specific & Modular

Aptazymes are RNA structures that combine self-cleaving ribozymes with a ligand-binding aptamer domain. The aptamer has specificity to bind to the target vitamin, while the self-cleaving ribozyme regulates the expression of the reporter gene as a riboswitch. These aptazymes are engineered through in vitro evolution, based on the choice of target ligand and its binding, making our system modular to virtually any small organic molecules [7].

Paper-based cell-free expression of biosensor
Accessible & Cheap

To ensure an accessible and affordable test, the genetic construct of the aptazyme-based biosensor, substrate, and the cell-free expression system are freeze-dried on a paper support for facile analysis and distribution [8].

Dedicated hardware
Robust, Quantitative, & Portable

Consistent quantitative measurements of the color change resulting from the level of targeted vitamins are made possible with our user-friendly dedicated hardware, which requires minimal expertise to use. The hardware consists of a light intensity sensor and heating supply to measure the absorbance and maintain the incubation temperature of the cell-free system containing the biosensor, respectively.

Integrated human practices

We engaged with our stakeholders and considered their values to get their input and perspectives on the design of AptaVita. By doing so, we ensured a successful and meaningful implementation of our project. Through a value-sensitive design, we analyzed different design options. These perspectives were integrated into our design choices during different design phases. Taken all together, we arrived at our final design that relies on responsible and collaborative innovation.

The Future Prospects of AptaVita

Driven to deliver an efficient solution for vitamin deficiencies, we developed a modular, quantitative, and accessible rapid diagnostic test. The data collection contributes to a better understanding of the problem, thereby providing an opportunity for future intervention programs. We believe that AptaVita has the potential to alleviate health- and socioeconomic issues related to vitamin deficiencies and therefore contribute to the United Nations’ Sustainable Development Goals [1, 9]. The modular aspect of our system allows AptaVita to be applied to other small molecules, overcoming the limitations of accessibility for analytical testing that may arise in the future. For example by detecting metabolites of prostate cancer, mycotoxins, and sex steroid hormones for male breast cancer [10, 11, 12]

Explore how AptaVita contributes to tackling hidden hunger!

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References

1. Global Nutrition Report. (2018). Chapter 3: Three issues in critical need of attention. Development Initiatives.
2. Muthayya, S., Rah, J. H., Sugimoto, J. D., Roos, F. F., Kraemer, K., & Black, R. E. (2013). The global hidden hunger indices and maps: an advocacy tool for action. PloS one, 8(6), e67860. https://doi.org/10.1371/journal.pone.0067860
3. World Health Organization. (2021). Micronutrients. Adopted from https://www.who.int/health-topics/micronutrients#tab=tab_1 on 27/09/2021.
4. Van de Poel, E., Hosseinpoor, A. R., Speybroeck, N., Van Ourti, T., & Vega, J. (2008). Socioeconomic inequality in malnutrition in developing countries. Bulletin of the World Health Organization, 86(4), 282-291.
5. World Health Organization. (2021). Vitamin and Mineral Nutrition Information System (VMNIS). Adopted from https://www.who.int/teams/nutrition-and-food-safety/databases/vitamin-and-mineral-nutrition-information-system on 27/09/2021.
6. Centers for Disease Control and Prevention, World Health Organization, Nutrition International, & UNICEF. (2020). Micronutrient Survey Manual. Geneva: World Health Organization.
7. Townshend, B., Xiang, J. S., Manzanarez, G., Hayden, E. J., & Smolke, C. D. (2021). A multiplexed, automated evolution pipeline enables scalable discovery and characterization of biosensors. Nature Communications, 12(1), 1-15. https://doi.org/10.1038/s41467-021-21716-0
8. Pardee, K., Green, A., Ferrante, T., Cameron, D., DaleyKeyser, A., Yin, P., & Collins, J. (2014). Paper-based synthetic gene networks. Cell, 159(4), 940–954. https://doi.org/10.1016/j.cell.2014.10.004
9. United Nations. (2021). Department of Economic and Social Affairs. Sustainable Development. Adopted from https://sdgs.un.org/goals on 27/09/2021.
10. Struck-Lewicka, W., Kordalewska, M., Bujak, R., Yumba Mpanga, A., Markuszewski, M., Jacyna, J., Matuszewski, M., Kaliszan, R., & Markuszewski, M. J. (2015). Urine metabolic fingerprinting using LC-MS and GC-MS reveals metabolite changes in prostate cancer: A pilot study. Journal of Pharmaceutical and Biomedical Analysis, 111, 351–361. https://doi.org/10.1016/j.jpba.2014.12.026
11. World Health Organization (2018). Mycotoxins. Adopted from https://www.who.int/news-room/fact-sheets/detail/mycotoxins on 04/10/2021.
12. Brinton, L. A., Key, T. J., Kolonel, L. N., Michels, K. B., Sesso, H. D., Ursin, G., Van Den Eeden, S. K., Wood, S. N., Falk, R. T., Parisi, D., Guillemette, C., Caron, P., Turcotte, V., Habel, L. A., Isaacs, C. J., Riboli, E., Weiderpass, E., & Cook, M. B. (2015). Prediagnostic sex steroid hormones in relation to male breast cancer risk. Journal of Clinical Oncology, 33(18), 2041–2050. https://doi.org/10.1200/JCO.2014.59.1602

A big thank you to our sponsors!