Diagnostic Assay using Piece of Paper?

With current technology in synthetic biology, scientists were able to diagnose using a piece of PAPER. Yes, that’s right a paper to identify your sickness.

Marco
ILLUMINATION
4 min readJan 14, 2023

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Photo by National Cancer Institute on Unsplash

By utilizing Cell-Free Protein Synthesis (CFPS) and biosensors for genetic material, scientists were able to detect viruses or bacteria and then give a specific signal to the operator, so they know what pathogen is inside the body.

Health is expensive!

The health sector is the second highest federal money spender in 2022 with $914 Billion. Around 93.8% of that budget goes toward grants to states for Medicaid, centers for medicare and Medicaid services, health and human Services meanwhile 5.3% goes to health research and training and the rest 0.9% goes to consumer and occupational health and safety.

Source: United States Federal Spending in 2022, Chart created using ggplot2 libraries in R

Currently, we are facing multiple biological threats such as antimicrobial-resistant microbes, monkeypox outbreaks, and ebola outbreaks in Democratic Republic of the Congo. What if suddenly there’s another pandemic like COVID? If another pandemic hit again most of the spending will be reallocated to handle it*. But what if we have a cheap and fast method to diagnose a disease? Surely that can

*Notes: I am not saying budget reallocation is a bad thing. But budget reallocation can reduce the effectiveness of other health programs because of changes in priority.

Color Changing Paper

But how does it work? Mainly it works by changing color. If the viruses are present within a patient, then it will turn into a certain color by utilizing a certain enzyme.

This invention is very useful, especially for laboratories that don’t have diagnostic equipment such as thermal cycler for PCR (golden standard for many diagnostics) and for remote areas that don’t have medical infrastructure such as South Africa.

Photo by Ilya Zoria on Unsplash

Currently, scientists were able to detect Noroviruses by using these papers. First, virus samples are captured using synbody (a biotin-labeled synthetic peptide affinity ligand) attached to a magnetic bead for enrichment. After that, Noroviruses RNA is amplified by a specific enzyme. The amplified RNA samples are added to the paper for diagnosis. The paper itself contains an RNA acting as a biosensor called toehold switch which can recognize specific RNA sequences. Amplified Noroviruses RNA will bind to the sensor which then will generate lacZα peptide and combined with lacZω will produce a purple color within the paper. If there are no Norovirus infections, then the paper will not produce a different color.

Lower Price!

The research claimed that the whole material cost for the paper diagnostic is $8.73 and if we also calculate the average lab technician (using South Africa standard) the total cost per assay is $14.02 meanwhile the current noroviruses diagnostic in South Africa is using RT-PCR method which cost around $14.93 (Prices with discount, if there is no discount the diagnostic can cost around $30.26-$155.44).

Now you might be thinking, “Hey the cost is not that much different, and PCR is the golden standard for many diagnostic assays, so why should I use it?”. Keep in mind that the $14.02 cost can still be reduced even further with the optimization of magnetic beads used for capturing virus samples and large scales order of materials. Also, as I mentioned before these paper test assay doesn’t need equipment such as thermal cycler which can cost more than $2000.

Stability and Activity

The scientist claimed that by using freeze-drying, cell-free system can be preserved for a year at room temperature.

Freeze-drying indeed creates sterile and gives properties for protein synthesis within abiotic material. Using this method, the paper biosensor could be stored at room temperature and ready for distribution. If the paper is needed, then you just need to activate it using water. However, with an increasing amount of storage time the functionality and output signal of the system decrease, thus making it less effective for assay as time passed. Currently, scientists are developing another method for the preservation of CFPS system without reducing the system’s effectiveness.

My thought

This innovation allows medical personnel in remote medical clinics or ships to diagnose pathogens without expensive equipment. Personally, I really wish that we can develop the method and equipment further, so we can diagnose our own bodies inside our homes without the need to go to a hospital or clinic (like COVID-19 self-test). It will help to reduce the burden on the healthcare system and prevent more death. There are many stories I heard about someone who underestimated symptoms in their own body and only go to the doctor once it hit the worst. Hopefully, this paper-based diagnostic can be developed for use at home.

Reference

Ma, D., Shen, L., Wu, K., Diehnelt, C. W., & Green, A. A. (2018). Low-cost detection of norovirus using paper-based cell-free systems and synbody-based viral enrichment. Synthetic Biology, 3(1), ysy018.

Wang, T., & Lu, Y. (2022). Advances, Challenges and Future Trends of Cell-Free Transcription-Translation Biosensors. Biosensors, 12(5), 318.

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Marco
ILLUMINATION

Microbiologist | Science communicator enthusiast