Lab-on-a-chip test has potential to detect COVID-19 immune response faster than current antibody testing
A new antibody test being developed by a team that includes two SMU researchers has the potential to detect the presence of antibodies generated in response to COVID-19 faster and with more accuracy than current antibody testing.
Antibody tests are key to helping determine how many coronavirus cases have gone undetected and whether people who have had the virus might now be immune—measurements that can help the healthcare community manage the COVID-19 pandemic and plan for the future. But conventional immunosensor antibody tests tend to be slow to show results and frequently inaccurate.
Researchers estimate the lab-on-a-chip test could detect immune responses to coronavirus in two to three minutes, with just a drop of blood. The materials used to create the test are inexpensive, which should result in low-cost mass production.
Ali Beskok and J.-C. Chiao are the lead researchers behind the lab-on-a-chip test.
Beskok is The Brown Foundation, Inc. Professor of Engineering at SMU's Lyle School of Engineering. Chiao is The Mary and Richard Templeton Centennial Chair and professor in Lyle's Department of Electrical and Computing Engineering. Together, they have more than 50 years of combined expertise in microfluidics technology and biotechnology.
Eva Csaky, Executive Director of SMU's Hunter and Stephanie Hunt Institute for Engineering & Humanity; Bob Hendler, Chief Medical Officer of Texas Hospital Association; and Quan-Zhen Li, Director of UTSW Genomics & Microarray Core Facility, were also consultants on the project.
To accelerate the development of the lab-on-a-chip device for potential clinical uses, the team is currently seeking research funding.
How it works
The lab-on-a-chip test will look for signs that a person's immune system has at some point responded to coronavirus being present in their body. Specifically, it will detect human IgG, IgM, and IgA antibodies that are produced when someone is or has been infected with the virus.
The test is performed by applying a drop of blood to a microfluidic chip used to analyze tiny amounts of liquid. A filter embedded in the microchip extracts plasma from the blood sample. The chip is then placed into an electronic instrument that uses electric measurements to detect whether specific antibodies are present in the plasma.
"Our device contains highly-sensitive electrodes that can specifically capture those targeted antibodies. Once captured, a signal will be generated to the attached electronics and send information to the user's smartphone," Chiao explained.
The chip is 2 cm in diameter, and the device is simple enough that those without medical training should be able to perform the test, Beskok noted.
How do these electrodes—conductors by which electrical currents can travel—know they have found a targeted antibody?
Antibody-Antigen Binding is the Key
An antigen is a protein that provokes the body's immune system to attack viruses, bacteria, or other harmful intruders to the body. Antibodies are the proteins that actually do the work of eliminating that intruder by attaching to antigens.
"We will use COVID-19 antigens such as Spike proteins (S1 and S2) that can be found on the surface of the virus. These protrude from the virus membrane, and the antibodies attach onto these," Beskok said. "These antigen proteins cover the electrode surfaces like a sticky pad, and only the specifically matched antibodies will attach on to these."
Beskok said the same technology can potentially be used to detect other diseases that have known antibody-antigen binding.
"The potentials are unlimited," Beskok said.
SMU (Southern Methodist University) has applied for a provisional patent of the technology behind the test, which is called Multiplexed Assay for the Immune Response to COVID-19 (MAIRC).
Beskok and Anil Koklu, who got his Ph.D. in mechanical engineering at SMU, first came up with the idea of using a "Lab on the Chip" device to detect malaria and tuberculosis in 2018.
They created an early prototype of this device, using lattice-like nanopillar structured electrodes created at the University of Texas at San Antonio. Results outlined in the journal Analytical Chemistry showed that the early device accurately detected IgG antibodies in 60 seconds using a small sample (just one ng/ml) of lab-bought antigens and antibodies.
Beskok and Chiao switched their focus to COVID-19 antibody detection once the global pandemic began. They and two SMU Ph.D. students have since made modifications to the device. For instance, they've made changes to the electronic equipment used to read the chip, so that the test can be performed anywhere via a smartphone.
They have also added an additional detection method to measure how much of each type of antibody—IgG, IgM, or IgA—is found in a sample. This allows doctors to better track a person's recovery to COVID-19, Chiao said. Because of the extra detection step, Beskok estimates it will take two to three minutes for someone using lab-on-a-chip testing for COVID detection to get results on their smartphone.
The next step in the research will be testing the sensitivity and specificity of the device using lab-purchased human plasma samples spiked with lab-purchased antibodies and antibodies. Beskok and Chiao will then test the device on plasma from actual COVID patients before it would be made available to the public.
The gold standard for antibody testing is the enzyme-linked immunosorbent assay, or ELISA. These tests require a person to go into a lab to have their blood drawn, and they typically take two days to get results back.
"There are some other techniques to detect antibodies quickly without using expensive laboratory equipment, but they suffer from sensitivity, accuracy, and consistency issues," Chiao said.
The precision and speed of lab on a chip are attributable, in part, to several innovations. One of those is the use of alternating current electrothermal (ACET) flows to bring antibodies in the blood plasma closer to sensor surfaces in the chip, so they can be detected.
"An analogy of ACET is this: think about using a fan to force the air to pass a filter. The filter can capture more dust and particles in the air this way," Beskok said. "Similarly, ACET allows the antibodies in the blood plasma to be captured more efficiently and detected by our device."
Beskok and Chiao estimate the cost of the electronic instrument to read the chip would be about $15 to $20. The cost of the disposable cartridge, which is where a drop of blood would go, would likely be less than $1.
"Our ultimate goal is to create quantifiable, accurate, fast, and inexpensive diagnostic methods based on the detection of human IgG, IgM, and IgA antibodies. This does not currently exist, and it would have a deep and significant impact on the world, given the devastating effect this coronavirus pandemic has had," Chiao said.