In today’s world, inexpensive and rapid medical diagnostic tests are needed more than ever. We believe that disposable electrochemical sensors can meet this need. Electrochemical sensors measure changes in electrical signals that are caused by binding events between antibodies and analytes. Like clinical RT-PCR tests, electrochemical detection provides a quantitative readout of virus concentration in a samples, but at testing rates more similar to the at-home tests. In short, electrochemical diagnostics enable rapid testing with less ambiguity.
Common electrochemical sensor electrodes are made from gold, which is wasteful for single-use devices. As an alternative, conductive carbon-based electrodes can be utilized. Graphene, a highly conductive, two-dimensional form of carbon, is an excellent candidate for electrode materials. Graphene films are an ideal material for electrochemical biosensing due to their high electrical conductivity, large surface area, and biocompatibility.
By combining emerging graphene ink technology with decades-old protein-linking chemistry, my collaborators and I designed a universal biosensing platform that could be produced at scale through various additive manufacturing techniques. These devices have been used for the rapid electrochemical detection of SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic. Through careful engineering, my team and I successfully developed printed biosensors that cost less than $4.00 per unit and, within 30 minutes, could electrochemically detect SARS-CoV-2 Spike RBD protein in artificial saliva at a limit of detection lower than most at-home COVID diagnostics on the market.
The Hersam group at Northwestern University and the Claussen and Gomes groups at Iowa State University have collaborated for years to adapt the graphene biosensing platform for various biosensing applications. Almost any antibody can be attached to the graphene surface, allowing the device to be customized for the detection of many types of molecules. As a first demonstration, we detected cytokines, which are immune system proteins that become elevated in the blood during states of infection. We were able to detect cytokines at levels that were medically relevant for diagnosing paratuberculosis in cattle. We also detected the small molecule histamine, which creates an inflammatory response in the body if ingested at sufficiently high concentrations. Rotting fish products can produce histamine, so we developed our sensor to detect histamine in fish broth at medically relevant levels.
Overall, the low cost of manufacturing and short testing time suggest that we can use this printed graphene biosensor platform for other sensing applications, including wearable health monitoring and human health diagnostics. Nevertheless, a few barriers to commercialization do exist. Manufacturing identical sensors that provide reproducible measurements is one challenge, although high-throughput manufacturing techniques like screen printing are beginning to overcome that limitation. Additionally, the accuracy of the sensor can be compromised if the surface of the electrode is not adequately treated to prevent adsorption of undesirable proteins and molecules that mask or imitate the signal from true antibody-analyte binding events. Still, a number of blocking agents and coatings have been developed to overcome this limitation.
The ultimate challenge to commercialization lies with the equipment required to measure the electrochemical signals from the sensor. The key instrument, called a potentiostat, ranges from the size of a desktop computer to a USB drive and represents the most expensive component of the electrochemical diagnostic kit. While similar devices have been mass-manufactured for electrochemically detecting other medical conditions – e.g. glucose meters for diabetes management – the technology is still not affordable enough to be used in a public health/epidemiology context.
Therefore, I see two possible paths forward for electrochemical biosensor commercialization.
1) Potentiostat technology for electrochemical diagnostics is refined and optimized to cost $20-50 per device for the US consumer.
2) Electrochemical diagnostics are pursued for use cases that can justify the higher operating costs.
Researchers at Harvard University chose the second path forward when testing their eRapid electrochemical sensor platform during the pandemic. First, the eRapid system was used in the R&D phase of COVID-19 diagnostic assays in Australia; this suggests that electrochemical diagnostics could become an important clinical tool to improve the performance of more-inexpensive lateral flow assays. Additionally, the Harvard team applied their electrochemical diagnostics in the hospital setting to develop a rapid sepsis assay, shortening testing time from 1 hour to 7 minutes and enabling higher-quality patient care in the process.
I hope to see more clinical applications of electrochemical diagnostics in the coming years.
Selected press coverage of graphene-based electrochemical sensors
- Phys.org: Histamine sensor
- National Institute for Food and Agriculture: Food safety sensor
- 3D Printing Industry: Food toxin sensor
My publications on graphene-based electrochemical sensors
C.C. Pola*, S.V. Rangnekar*, R. Sheets, B.M. Szydlowska, J.R. Downing, K.W. Parate, S.G. Wallace, D. Tsai, M.C. Hersam, C.L. Gomes, J.C. Claussen. “Aerosol-jet-printed graphene electrochemical immunosensors for rapid and label-free detection of SARS-CoV-2 in saliva.” 2D Materials, 9, 035016 (2022).
S.G. Wallace, M. Brothers, Z. Brooks, S.V. Rangnekar, D. Lam, M. St. Lawrence, W. Gaviria Rojas, K.W. Putz, S. Kim, M.C. Hersam. “Fully printed and flexible multi-material electrochemical aptasensor platform enabled by selective graphene biofunctionalization.” Engineering Research Express, 4, 015037 (2021).
K. Parate*, C.C. Pola*, S.V. Rangnekar*, D.L. Mendivelso‐Perez, E. Smith, M.C. Hersam, C.L. Gomes, J. Claussen. “Aerosol‐ jet‐printed graphene electrochemical histamine sensors for food safety monitoring.” 2D Materials, 7, 034002 (2020).
K. Parate*, S.V. Rangnekar*, D. Jing, D.L. Mendivelso‐Perez, S. Ding, E.B. Secor, E.A. Smith, J.M. Hostetter, M.C. Hersam, J.C. Claussen. “Aerosol‐jet‐printed graphene immunosensor for label‐free cytokine monitoring in serum.” ACS Applied Materials and Interfaces, 12, 8592‐8603 (2020).
Sonal V. Rangnekar 