Wyss-founded StataDX is using eRapid’s portable electrochemical sensing technology to develop point-of-care diagnostics for neurological, cardiovascular, and renal diseases.
The Problem
Many diseases and disorders cannot be diagnosed at the point-of-care, including at physician offices, pharmacies, and peoples’ homes. This prevents patients from receiving the best possible care and therapy on the fastest route. Compounding this problem is the fact that a large number of those disorders cannot be detected by measuring one disease-signaling biomarker molecule alone, but require the specific and sensitive assessment of multiple biomarkers that only in combination enable an accurate diagnosis.
A solution would be portable electrochemical sensors that translate the highly specific and sensitive chemical detection of multiple biomolecules present in a small sample of blood or other bodily fluid into electrical signals whose strength correlates with the levels of bound target biomolecules, and which can be immediately read and interpreted. Electrochemical sensors have revolutionized at-home medical testing for diabetics. However, they have not been successfully applied to the diagnosis of other conditions. The root cause has been the “biofouling” of electrochemical sensors, which is caused by microbial and other biomolecules in biofluids that attach to the sensor surfaces and prevent the transfer of the electrons to produce the electrical signal. Biofouling renders electrochemical sensors useless within a short time, blocking their advance into real-world diagnostic applications.
Our Solution
A multidisciplinary team at the Wyss Institute has developed an affinity-based electrochemical sensor technology as a low-cost multiplexed diagnostics platform that can simultaneously detect and quantify a broad range of biomarkers with high sensitivity and selectivity in a small volume of blood or other complex biological fluids.
The foundational discovery made by the team was a novel antifouling nanocomposite coating that enables electrodes in electrochemical sensors to withstand the attack of biofouling molecules contained in various biofluids, including blood. As a result, the electrodes’ sensing capabilities are maintained over weeks of continuous use, and potentially interfering background signals are minimized. The team then integrated their coated electrodes with a process that causes a chemical precipitate to form in solution and fall onto the electrode surface in response to the binding of a target biomolecule. This changes the electrical conductivity of the electrode, which can be easily detected using an electronic readout. The precipitation process can be independently performed on neighboring electrodes of an electrode array, with each electrode detecting a different biomarker without signal interference, and the electrode-bound precipitate can be stably maintained for more than a week.
Importantly, the anti-fouling coating can be used to embed probes for a broad range of biomarkers, including proteins, antibodies, metabolites, hormones, and RNA molecules, that can be simultaneously detected in a drop of blood or saliva using multiplexed electrode arrangements. In their validation process, the team developed multiplexed eRapid sensors for the detection of various complex disorders. The combined capabilities of eRapid opened up a vast diagnostic space with multiple opportunities for commercialization.
Product Journey
The early development stages of the eRapid technology were funded by a Defense Advanced Research Projects Agency (DARPA) grant awarded to Wyss Founding Director Donald Ingber, M.D., Ph.D., which focused on building a human body on-a-chip. Additional support was provided by the KeepSmilin4Abbie Foundation as part of Project Abbie. After the initial technological eRapid-enabling discoveries, the team, led by Ingber and Senior Staff Scientist Pawan Jolly, Ph.D., advanced the technology through Wyss Institute-funded Validation and Institute Projects. To maximize its commercial potential, the team improved on their original coating by developing a graphene-nanocomposite chemistry that enhanced the efficiency of eRapid sensors, and inventing a novel “dip coating” method to dramatically reduce the cost and time of manufacturing. The latter advance also enabled eRapid sensors to be stored for an extended period of time with minimal performance loss, making them especially useful in settings where samples are collected locally and then sent to a central lab for analysis.
The researchers developed electrochemical sensors for 30 different disease-specific biomarkers with a vast range of sizes (100 Da to 150 kDa) and belonging to different classes of biomolecules. Multiplexing different eRapid sensors in sensor arrays enabled the team to detect difficult-to-diagnose disorders ranging from sepsis to brain concussion and myocardial infarction quickly and accurately.
We showed in our extensive de-risking process at the Wyss Institute that the eRapid platform can address diverse live-threatening diseases and conditions with multiplexed biomarker measurements for which no accurate diagnosis existed before.
From 2020 onwards, the COVID-19 pandemic became another driving force for the eRapid team’s de-risking process. With partners from industry and affiliated hospitals, they developed SARS-CoV-2-specific eRapid sensors that could be expanded to determine the presence and stage of viral infections as well as the patient’s immune responses, all simultaneously and at the point-of-care.
The team started to form ties with Boston’s biotech ecosystem and in 2021 obtained additional funding from MassVentures for advancing their technology after being selected as the winner of its MALSI+ competition, which “is the Commonwealth of Massachusetts’ flagship event connecting scientific innovators, entrepreneurs, business leaders, and investors.”
In 2022, Ingber and Jolly co-founded StataDX together with external co-founders Sidhant Jena, CEO and Michal Depa, CTO. Sanjay Sharma Timilsina, Ph.D., and Nolan Durr, two Wyss researchers who were instrumental in advancing the eRapid platform through its different stages, joined StataDX’s external co-founders in the Cambridge-based startup.
While there are many at-home tests for viral diseases such as COVID-19 available today, nothing yet exists for patients with complex chronic diseases such as multiple sclerosis, heart failure or chronic kidney disease that need periodic measurements of multiple biomarkers. The approach enabled by eRapid addresses underlying limitations of electrochemical biosensing in an elegant way, which may overcome the challenge faced by so many promising diagnostic technologies – the successful transfer to manufacturing at scale.
StataDX has licensed eRapid to enable new diagnostics for neurological, cardiovascular, and renal diseases, and is first focusing on the detection of neurological disorders in various point-of-care settings.