A reaction on a single electrode can tell scientists a remarkable amount about the chemical nature and amount of analytes involved.
The challenge comes when they want to distinguish many reactions on the same electrode.
After more than a decade of trying to overcome that limitation, Ravi Saraf and his Nebraska Engineering graduate students have demonstrated a way to quantify many reactions on the same electrode without sacrificing extraordinary sensitivity.
The advancement, Saraf said, could potentially lead to better early diagnoses of diseases such as cancer and improved assessment of injury from exposure to high-energy radiation.
“It is certainly one of the more exciting things I’ve done,” said Saraf, Lowell E. and Betty Anderson Distinguished Professor of chemical and biomolecular engineering.
In two recently published studies, Saraf and graduate students Linh Hua, Md Tawfiq Anik and Joydip Dey describe an optical-electrochemical technique capable of detecting reactions involving just zeptomoles, each of which include roughly 600 molecules, while probing different locations on the same electrode.
The results bring the technology close to a fundamental quantum mechanical limit imposed not by the instrument but by the statistical error in counting electrons involved in a reaction.
Electrochemical sensors are everywhere, with the glucose meter perhaps the most familiar example. But conventional sensors measure the total electrical current produced on an electrode’s surface, making it difficult to distinguish multiple reactions occurring simultaneously.
Saraf’s team took a different approach.
Their lab-built instrument, the Scanning Electrometer for Electrical Double-layer (SEED), uses light to measure multiple reactions on a single electrode.
The researchers attached methylene blue molecules to DNA on a gold electrode. As the molecules underwent reduction and oxidation reactions, they switched between colored and colorless states. SEED measured those changes optically.
That sidesteps a longstanding obstacle. Increasing the speed of an electrochemical reaction increases the signal, but also the capacitive background that can overwhelm it. Because SEED measures an optical change instead of that electrical background, Saraf said, “this device is sort of blind to that.”
That allowed the team to operate at higher speeds and achieve extraordinary sensitivity.
In a study published in the September 2026 edition of ACS Measurement Science Au, Saraf’s team reported detecting redox reactions of about eight zeptomoles (roughly 4,800 molecules) and had effectively reached what Saraf calls the “quantum mechanical wall.”
At that scale, unavoidable statistical fluctuations associated with counting electrons become significant. Researchers can also move the laser across the electrode to examine individual spots, potentially enabling quantitative detection of many analytes on one chip under identical conditions using a small sample.
“That was a remarkable result,” Saraf said.
A second paper, published in October in ACS Sensors, demonstrated what the researchers call “reactivity amplification.” The system quantified 250 zeptomoles of target molecules, roughly 150,000 molecules, on a spot about 20 micrometers across. About 2% binding of target molecules produced a 27% change in the SEED signal.
Those capabilities could eventually matter far beyond the laboratory.
One application Saraf is pursuing involves microRNAs, regulatory molecules whose concentrations in blood can change with disease. Detecting multiple microRNAs at extremely low concentrations could potentially aid early disease detection or assessment of radiation exposure.
Saraf envisions the technology primarily as a clinical or laboratory instrument, with continued development aimed at making it smaller and practical for real-world use.
Its reach may extend beyond medicine. Testing numerous electrochemical reactions on the same chip under identical conditions could allow researchers to rapidly compare catalysts, corrosion-resistant materials and other chemical systems.
“We can do hundreds of reactions on the same chip in the same beaker under the same condition,” Saraf said.
For Saraf, the accomplishment is especially satisfying because the work began outside his expertise. He was not an electrochemist and began teaching himself the field from the ground up.
Rather than beginning with conventional electrochemical methods, Saraf approached the problem through something he already understood: optics. If an electrochemical reaction changes a molecule’s electrical charge, he reasoned, perhaps that change could be detected with light rather than relying solely on electrical current.
“The idea of using optics to measure electrochemical reaction is decades old,” Saraf said. “Our innovation was a simple method that allowed us to measure reaction at very fast rates and push farther than we’ve ever gone before.”
This work was supported by the National Institutes of Health (R01GM157477).
