Diagnostics in your hand
Handheld electrochemical sensors are part of the daily routine for millions of people with diabetes around the globe who monitor their blood sugar levels with electric glucometers. While such sensors have revolutionized at-home medical testing for diabetics, they have not yet been successfully applied to diagnosing other conditions.
Sensors like glucometers detect glucose in blood based on the activity of an enzyme, and there are only a limited number of enzymes that can be used to sense biomarkers of human disease. An alternative detection strategy based on binding events between antibodies and their molecular targets have been investigated to expand the use of electrochemical sensors for medicine, but these sensors fall victim to the rapid accumulation of “fouling” substances from biological fluids on their conductive surfaces, which deactivate them. Existing antifouling coatings are difficult to mass-manufacture, suffer from quality and consistency issues, and are not very effective. Now, a new diagnostic platform technology developed by researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University known as “eRapid” enables the creation of low-cost, handheld electrochemical devices that can simultaneously detect a broad range of biomarkers with high sensitivity and selectivity in complex biological fluids, using as little as a single drop of blood. The technology is described in Nature Nanotechnology.
“As long as an antibody exists for a given target molecule, eRapid can detect it,” said co-author Pawan Jolly, Ph.D., a Senior Research Scientist at the Wyss Institute. “By solving the biofouling problem with a simple yet robust design, we are now able to easily mass-produce biochemical sensors for a wide variety of applications at low-cost.” The team demonstrated the commercial utility of this approach by creating a multiplexed sensor with three separate electrodes, each coated with the BSA/gold nanowire matrix and a layer of antibodies against a specific clinically relevant target molecule: interleukin 6 (IL6), insulin, or glucagon. When they incubated the sensor with the respective target molecules in undiluted human plasma, they observed excellent electrical signals with picogramper- mL sensitivity. Conversely, electrodes coated with a published “PEG-SAM” anti-fouling coating failed to produce distinct signals, indicating that they had been irreversibly fouled by off-target molecules in human plasma samples. In addition, the BSA/gold-nanowire-coated sensors can be washed and reused multiple times with minimal signal loss, allowing serial monitoring of biomarkers easily and at low cost.
Since then, the Wyss team has been able to detect more than a dozen different biomarkers ranging from 100 Da to 150,000 Da in size with eRapid, and they are continuing to experiment with conductive nanomaterials to optimize the electrode coating and the system’s performance, as well as reduce the cost even further.