Take MIE Breath Away

The inhalation of SARS-CoV-2 containing aerosols is thought to be the predominant mode of infection, but why not use this distinctive transmission feature to combat COVID-19 – by detecting the virus in exhaled breath?

Researchers modified a micro-immunoelectrode (MIE) biosensor to create a breath aerosol analyzer that can rapidly detect SARS-CoV-2 for direct, non-invasive screening (1).

We spoke with lead and corresponding authors from Washington University in St. Louis: Dishit Ghumra and Rajan Chakrabarty, from the Center for Aerosol Science and Engineering, John Cirrito from the Department of Neurology, and Carla Yuede from the Department of Psychiatry, to learn more about their research and their ambitions for the diagnostic device.

What was the inspiration behind your MIE biosensor – and how does it work?
 

Our MIE biosensor is actually adapted from an Alzheimer’s disease-related technology that was originally developed in John Cirrito’s lab at Washington University in St. Louis, USA. That device worked by attaching an antibody specific to amyloid-β to the surface of a carbon fiber microelectrode. 

Our biosensor is also an antibody-based sensor, but we attach a llama-derived nanobody specific to SARS-CoV-2 onto the surface of a screen-printed carbon electrode. The MIE biosensor measures the oxidation of tyrosine amino acids within the SARS-CoV-2 Spike protein. Linked to a standard potentiostat, square wave voltammetry is conducted to oxidize tyrosine, gauging the peak oxidation current that signifies the presence of virus aerosols in a given sample. The major advantage of our MIE biosensor is the really low limit of detection (LoD), as it can detect as low as ~8 viral copies in exhaled breath samples.

And the intended application is rapid point-of-care testing?
 

That’s right. In fact, the most challenging part of our research was meeting the three characteristics important for mass testing applications: i) an affordable, non-invasive, and single-use sample collection device, ii) an ultrasensitive biosensor that provides rapid results, and iii) operation that does not require the need for trained personnel or additional processing steps.

Through meaningful collaborations between the Washington University in St. Louis School of Engineering and the School of Medicine, we were able to overcome these challenges: the Engineering team came up with an ideal design for a breath aerosol collection device that can be 3D-printed (affordable), while the School of Medicine team developed the MIE biosensing technology for rapid detection of the sampled virus aerosols.

Did you successfully meet your initial goals? 
 

We have successfully demonstrated a cost-effective point-of-care testing platform that delivers results within a minute – so, yes!

This non-invasive technique offers rapid and point-of-care detection without the need for specialized training. Notably, just 20 seconds of sampling (two breaths) yielded reliable results, contrasting with typical exhaled breath condensate (EBC)-based studies. The MIE biosensor exhibited high sensitivity for SARS-CoV-2 detection, outperforming comparable devices. Our testing platform also has the potential for multiplexed detection of different respiratory viruses, including influenza and RSV.

Tell us more about the low LoD – were you surprised by what you achieved? 
 

Actually, we anticipated that the MIE biosensor’s LoD would be low, especially when compared with RT-PCR techniques that can achieve a LoD of about as 100 copies/mL. However, our series of experiments involving sequential dilution with different SARS-CoV-2 variants, aimed at assessing the biosensor's sensitivity, revealed an impressive LoD range of 8-32 copies/mL (for Beta, Delta, Washington WA1, and Omicron BA1 variants). These findings further underscore the platform’s capability to identify viral particles in as low as two exhaled breaths of patients.

What impact do you think the MIE biosensor will have on healthcare professionals and patients?
 

Our device has the greatest potential in mass testing scenarios, particularly in settings where significant gatherings occur, such as airports, conference centers, and sports arenas. Its primary advantage lies in its ability to non-invasively and rapidly detect SARS-CoV-2 in infected individuals. The swift turnaround time holds the promise of early intervention and effective containment of disease transmission within communities.

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