COVID-19 & Corporate Wellness

In Microfluidics, Speed Meets Accuracy to Rapidly Verify Infection and Limit Infectious Spread in the Workplace

Richard H. Noel, M.S.
Director North American Marketing

Workplace-based testing for SARS-CoV-2, the virus that causes COVID-19, could identify workers with SARS-CoV-2 infection, and thus help prevent or reduce further transmission[1], but with all these tests coming out, which one should you choose to screen asymptomatic employees, to improve your chance to catch silent spreaders? If you’re like many others on executive teams, you didn’t get a Ph.D. in clinical laboratory medicine on the side. You likely just want to know a little about the test technology to create a safe working environment. One where your employees feel comfortable returning to work and reduce the risk of an outbreak.

Rapid antigen tests, those that look for a protein unique to SARS-CoV-2, are emerging as the pragmatic solution to viral testing in the community. They are fast – usually providing results in 12-30 minutes, they are easy to use, and they are appropriately priced for large-scale testing. But what about the sensitivity you may be thinking? Aren’t they less accurate than PCR? The answer is a bit more complex.

Some antigen tests are more sensitive than others. It depends on the test technology. A low-sensitivity test means more false negatives, which means some infected individuals harboring the virus are able to co-mingle with the rest of the workforce undetected. Higher sensitivity tests can detect smaller amounts of virus thereby reducing the rate of false-negative results from infected individuals. Often, individuals can be contagious even when they’re not showing symptoms. These individuals can be pre-symptomatic, mildly symptomatic, or even never show symptoms yet still are able to transmit the virus to others.

Antigen-based testing technology used at the ‘point of care' can be separated into two categories, lateral flow antigen tests, which are more familiar, and microfluidic antigen tests, which represent the next generation in point of care testing technology. What’s the difference between microfluidic antigen tests and lateral flow antigen tests? Prior to the pandemic these were esoteric terms typically confined to conversations within the four walls of the hospital laboratory; however, with the emergence of next-generation point of care testing, it’s important to highlight the differences between these two technologies and what it means for SARS-CoV-2 antigen testing. In short, not all antigen assays are the same.

Lateral flow antigen tests have been around for decades. They use passive capillary action to drive an immunochromatographic assay. To give a more familiar example, if you put half a paper towel in a cup of water, the water will climb up the dry part of the paper towel through a process called capillary action. It’s the same principle for the driving force behind lateral flow antigen tests. Simply, the liquid sample is absorbed throughout the test pad, eventually crossing a lawn of antibodies designed to capture proteins unique to the SARS virus. Results are then visually determined by subjective observation often by non-laboratory trained personnel, picture a visually read pregnancy test where 1 line means the test worked and 2 lines mean you’re pregnant. Counting one line or two can be challenging especially when one line is very faint, which occurs when the concentrations of what you’re trying to detect are near the lower limit of detection. This leads to misinterpretation of results. More recently, in an effort to improve readability and sensitivity these lateral flow antigen tests use a different type of fluorescent dyes and are coupled with a digital reader. These simple tests are cheap, portable, and provide results quickly; however, notable limitations on sensitivity present challenges for SARS-CoV-2 testing. Requirements for higher concentrations of analyte to detect a positive signal constrain the sensitivity. They work well to rapidly identify infectious individuals with the highest viral loads, but performance is mitigated in individuals with relatively lower viral loads but who may still be contagious. In an effort to overcome the limitation of insensitivity, most if not all lateral flow antigen tests need to be used multiple times on the same patient within a 24–48-hour window. Testing at different points in time, also referred to as serial testing, may be more likely to detect acute infection among workers with repeat exposures than testing done at a single point in time. Notably, these so-called “rapid lateral flow antigen tests”, when used properly, actually take at least 24 hours and 15 minutes to provide a result. Emerging next-generation microfluidic antigen testing is anticipated to become the dominant architecture over the near term.

Next-generation, microfluidic, point-of-care antigen tests use more advanced technology to mimic complex lab analyzers but are scaled down to a fit on a single chip – hence the term, lab-on-a-chip. This new class of point of care tests uses microfluidic systems to miniaturize the complex lab processes, which until now, have only been available in more sophisticated hospital laboratories. Microfluidic devices have microchannels ranging from less than a micron to a few millimeters thick. To compare, human hair is about 100 microns thick. Microfluidics has been increasingly used in the biological sciences because precise and controlled experiments can be conducted at a lower cost and faster pace. These novel systems actively manipulate microliter volumes with nanoliter levels of precision to deliver exceptional performance at the point of care. The microfluidic architecture can not only control mixing to accelerate reaction kinetics but also control the analytical environment by washing away residual specimens providing a higher resolution analysis. When compared to lateral flow antigen tests, this liquid-free analysis provides a four-fold improvement in the limit of detection (LoD). These tests also precisely control reaction times and temperatures. Reaction times in microfluidic systems are much quicker than conventional devices due to the smaller dimensions of the systems leading to a shorter diffusion time for any given molecule.[2] Integrating these assets onto a single test strip provides the potential to revolutionize POCT by bringing the higher-performing technology out of the conventional hospital laboratory and closer to the patient.

SARS-CoV-2 testing demand is driving the adoption of this novel technology in a variety of settings from traditional healthcare settings outward to mobile clinics, on-site clinics, and near-site clinics within schools, workplaces, and large events. Rapid microfluidic SARS-CoV-2 antigen tests are designed to detect the presence of nucleocapsid protein (N) at lower concentrations than what is typically feasible on POC lateral flow antigen test platforms. These high-sensitivity, Rapid Microfluidic Immunoassays have important implications in terms of how, where, and when a test can be used for pandemic control.

We need rapid, accurate testing to fight COVID-19, because organizations, doctors, and individuals need to know if people are infectious, even when they are not symptomatic. But neither PCR nor conventional lateral flow antigen tests are optimized to meet those needs. The exceptional analytical sensitivity from rapid microfluidic tests for SARS-CoV-2 nucleocapsid antigen is just right: they are fast, easy to use, low cost, and accurate; unlike PCR they’re not designed to detect RNA so they won’t detect remnant RNA from previously infected - but now recovered - non-infectious individuals.[3] Recovered patients can continue to have SARS-CoV-2 RNA detected in their upper respiratory specimens for up to 12 weeks after symptom onset.[3],[4],[5] Investigation of 285 “persistently positive” adults, which included 126 adults who had developed recurrent symptoms, found no secondary infections among 790 contacts to these case-patients. Efforts to isolate replication-competent viruses from 108 of these 285 case-patients were unsuccessful.[3] Basically in this study a bunch of people kept testing positive by PCR but weren’t found to be contagious. Imagine sending your star performers home for 10 days of isolation because they tested positive by PCR but didn’t show symptoms and were no longer contagious.

Winning the war against the pandemic will require extinguishing the wildfire of infectious spread in the community and workplace. Tests that rapidly and accurately identify infected individuals who may still be contagious, while being sufficiently inexpensive and easy to use to allow frequent testing, can be a powerful tool for breaking the chain of transmission and preventing future flareups.[6] PCR is the premier finder of nucleic acids, bar none. But molecular detection does not necessarily denote the presence of a recoverable infectious virus. Recent data from a lab at Johns Hopkins suggests that antigen tests, not PCR, correlates better with viral culture, which is considered the best available proxy for infectivity.[7] Recovering patients that are no longer infective can actively shed viral RNA, at levels easily detected by PCR, for weeks or possibly months.[8] Detecting all viral shedders is an expensive luxury that does not necessarily serve society’s best interests.


Antigen-based testing, by contrast, could help to rapidly identify people who have high levels of virus — those who are most likely to be infectious to others — and isolate them from the community. However, not all antigen tests are the same. Lateral flow antigen tests provide rapid results but may come up a bit short as they’re only authorized for use in patients presenting within five or seven days following symptom onset, depending on the vendor. This may not provide sufficient sensitivity to cover the full range of infectivity, which can be as long as 10 days.[3] On the other hand microfluidic SARS-CoV-2 assays have been shown to maintain high performance through the 12th day following symptom onset.

What society really needs is a point of care test sensitive enough to adequately cover the broadest range of contagiousness, provide results quickly, and at a reasonable cost enabling widespread implementation across a variety of use-cases. Unlike lateral flow antigen tests, the emerging, next-generation microfluidic technologies simplify, scale down, and integrate techniques used in laboratory analyzers to provide lab-comparable diagnostic tests that can be easily used in community care settings. One system is authorized by FDA for emergency use during the COVID-19 pandemic for use on patients presenting up to 12-days post symptom onset, has superior sensitivity over most lateral flow assays, allows for the longest testing window currently available in waived settings, and shows a high positive predictive agreement (PPA) when compared to RT-PCR.[11] Microfluidic antigen tests combine speed with lab-grade performance to quickly catch the infectious of the COVID-19 pandemic while minimizing false alarms.


  1. SARS-CoV-2 Testing Strategy: Considerations for Non-Healthcare Workplaces.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 17 Mar. 2021, 
  2. Convery N, Gadegaard N. 30 years of microfluidics. Micro and Nano Engineering. Published January 26, 2019. Accessed May 1, 2021. 
  3. Interim Guidance on Duration of Isolation and Precautions for Adults with COVID-19. Centers for Disease Control and Prevention. Published February 13, 2021. Accessed May 1, 2021. 
  4. Li N, Wang X, Lv T. Prolonged SARS‐CoV‐2 RNA shedding: Not a rare phenomenon. Wiley Online Library. Published May 22, 2020. Accessed May 1, 2021. 
  5. Liu W-D, Chang S-Y, Wang J-T, et al. Prolonged virus shedding even after seroconversion in a patient with COVID-19. Journal of Infection. 2020;81(2):318-356. doi:10.1016/j.jinf.2020.03.063 
  6. Mina MJ, Parker R, Larremore DB. Rethinking Covid-19 Test Sensitivity — A Strategy for Containment. New England Journal of Medicine. 2020;383(22). doi:10.1056/nejmp2025631 
  7. Pekosz A, Parvu V, Li M, et al. Antigen-Based Testing but Not Real-Time Polymerase Chain Reaction Correlates With Severe Acute Respiratory Syndrome Coronavirus 2 Viral Culture. Clinical Infectious Diseases. January 2021. doi:10.1093/cid/ciaa1706 
  8. Guglielmi G. Fast coronavirus tests: what they can and can't do. Nature News. Published September 16, 2020. Accessed May 1, 2021. 
  9. Arons MM, Hatfield KM, Reddy SC, et al. Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility. New England Journal of Medicine. 2020;382(22):2081-2090. doi:10.1056/nejmoa2008457 
  10. Walsh KA, Spillane S, Comber L, et al. The duration of infectiousness of individuals infected with SARS-CoV-2. Journal of Infection. 2020;81(6):847-856. doi:10.1016/j.jinf.2020.10.009 
  11. Drain PK, Ampajwala M, Chappel C, et al. A Rapid, High-Sensitivity SARS-CoV-2 Nucleocapsid Immunoassay to Aid Diagnosis of Acute COVID-19 at the Point of Care: A Clinical Performance Study. Infectious Diseases and Therapy. February 2021. doi:10.1007/s40121-021-00413-x

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