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Undergrad Dhruv Biswas works with PhD student Wihan Adi in the lab
March 23, 2022

By delivering more details, biosensor boosts antibody testing

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In the future, with a finger prick and a portable testing device featuring a biosensor, a light source and a camera, you might be able to check your antibody levels against an infectious disease like COVID-19 without leaving home.

The benefits of such a test could be great: Local governments could use community data to inform prevention policies; epidemiologists could draw on large swaths of data to improve their models of disease spread; clinicians could tailor recommendations about boosters to individual patients based on their antibody levels; and vaccine makers could more easily monitor patient data and better understand their products’ effectiveness against different viral variants.

However, that vision requires antibody tests that are both more advanced than those currently commercially available, yet don’t require costly and labor-intensive laboratory analysis. Filiz Yesilkoy, an assistant professor of biomedical engineering at the University of Wisconsin-Madison, is working at the intersection of nanotechnology and photonics to deliver those kinds of tools.

Filiz Yesilkoy

In a new paper published in the journal Biomedical Optics Express, Yesilkoy, two of her students and Associate Professor Miriam Shelef from the UW-Madison School of Medicine and Public Health present a biosensor and accompanying imaging approach that delivers a more comprehensive COVID-19 antibody readout than commercially available tests. It’s an early-stage demonstration of technology that could power more advanced at-home or point-of-care serology tests in the future.

Whereas most existing serology tests check indiscriminately for any and all antibodies, and antigen tests look for one specific protein on a virus or bacteria (think COVID’s well-known “spike” protein), this nanoengineered biosensor delivers a more detailed picture. It’s capable of accommodating multiple antigens; for the paper, the researchers outfitted it with both the COVID spike protein and a nucleocapsid protein.

But the biosensor doesn’t merely detect the presence of those antigens.

“We can actually quantify how many antibodies, because our sensor enables that,” says Yesilkoy. “The number of antibodies we have may correlate to how well we’re protected. It’s also important to understand what antigen these antibodies are specific to so that we can identify cues relating to medical conditions and disease protection. Our sensor can do that, and it can do it in a very simple way.”

For their testing workflow, the researchers leveraged a syringe-like microfluidic cartridge prototyped by a team of undergraduates in the Department of Biomedical Engineering’s design course sequence that filters the serum from a small quantity of blood and transfers it onto the nanofabricated biosensor chip without requiring complex equipment. Optical analysis can then reveal a detailed antibody landscape from the sample.

While Yesilkoy, PhD student Wihan Adi and undergraduate Dhruv Biswas relied on more complex spectroscopy to pinpoint the suitable range of light wavelengths for that analysis in COVID patient samples (courtesy of Shelef), Adi notes their work paves the way for that component to be carried out using a basic portable optical reader using a proper optical filter.

A less complex optical analysis is an essential component for enabling point-of-care testing in settings such as local healthcare clinics, pharmacies or schools, a natural earlier step in the path toward true at-home testing. That’s precisely why Yesilkoy earned funding from the School of Medicine and Public Health’s Wisconsin Partnership Program for the project.

“It would be fantastic for low-income areas, as well as areas that don’t have antibody detection easily available to people,” says Biswas, a junior who’s planning to pursue a master’s degree through the BME department’s one-year accelerated program after graduation.

Moving forward, Yesilkoy says her lab plans to examine whether it can use this approach to detect specific viral variants in blood samples, work that could inform epidemiological studies. And yet even as the COVID-19 pandemic continues to provide immediate impetus for the research, the biosensor could easily be modified for future infectious diseases or more routine diagnostic checks.

“This could be generalized,” says Adi, who is the paper’s first author. “Let’s say you want to detect some kind of cancer biomarker or even something like hormone levels, something more routine and benign.”


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