Tag: graphene

Graphene, COVID-19, and Electrochemical Diagnostics

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

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).

What are 2D Materials?

Understanding 2D materials with pencil and paper.

Two-dimensional (2D) materials are a subclass of nanomaterials that are becoming increasingly popular for their electronic, optical, and mechanical properties. These materials are considered two-dimensional because of their atomically thin, planar geometry.

To understand the origins of 2D materials, you might envision a ream of printer paper. The ream is made up of many pieces of planar paper stacked on top of one another. Each sheet of paper shares physical and chemical properties with the aggregate ream. Both are white and good writing surfaces. Both the single sheet of paper and the ream will burn when exposed to a flame in air. However, there are other properties that are unique to the sheet sheet of printer paper. The single sheet is flexible and can be torn easily. The thin sheet of paper is more transparent when held up to light. Furthermore, the ream of paper is loosely bound. The addition of some energy – say, dropping the ream on the floor – will cause the stack to split up into individual pieces of paper. 

In this analogy, the individual sheets of paper represent 2D materials, and the whole stack is what we call a layered crystal. While the layered crystal and 2D material share some properties, there are more interesting electronic, optical, and mechanical phenomena that emerge when we “exfoliate” a layered crystal down to the atomically thin, single-layer limit. This exfoliation is achieved because the bonds between in-plane atoms (that is, the connections within a single sheet of paper) are much stronger than the out-of-plane, van der Waals bonds (the pieces of paper are loosely stuck to one another).

The most well-known layered crystal is graphite – the material that is found in pencil lead. Graphite is made up of layers of carbon atoms. When you write with a pencil, portions of the graphite crystal slip past one another due to the weak van der Waals bonds. This is a very crude exfoliation process; the portions of graphite that are left behind on the paper are still thousands-to-millions of times thicker than a single layer of the carbon atoms. However, with a little bit of scotch tape, graphite can be thinned to graphene – a single layer of carbon atoms.