Programmable Biosensor Chip Uses Single Molecules to Detect Multiomic Molecular Interactions

Source: National Academy of Sciences, written by Carl W. Fuller; Pius S. Padayatti; Hadi Abderrahim; Lisa Adamiak; Nolan Alagar; Nagaraj Ananthapadmanabhan; Jihye Baek; Sarat Chinni; Chulmin Choi; Kevin J. Delaney; Rich Dubielzig; Julie Frkanec; Chris Garcia; Calvin Gardner; Daniel Gebhardt; Tim Geiser; Zachariah Gutierrez; Drew A. Hall; Andrew P. Hodges; Guangyuan Hou. AI-generated summary by biochip.com, published July 29, 2026. Not independently reviewed.

A team spanning the University of California, San Diego, Harvard Medical School, Rice University, and Roswell Biotechnologies has built a programmable molecular electronics chip designed to measure molecular interactions one molecule at a time. The semiconductor device integrates single-molecule sensors into a scalable circuit, allowing it to detect electrical signals produced when biological molecules bind or react. Its demonstrated chip contains 16,000 independent sensors, each able to monitor a solution placed over the array. Rather than relying on fluorescent or chemical labels, the platform reads tiny changes in electrical current directly. That approach could let researchers observe how DNA, proteins, enzymes, antibodies, and other biological components interact in real time. The researchers reported the work in the Proceedings of the National Academy of Sciences, describing a platform for measuring binding kinetics and enzyme activity. By pairing molecular-scale sensors with semiconductor manufacturing concepts, the device aims to make detailed molecular measurements more scalable. The result is a chip-centered approach to multiomic measurement, meaning it can potentially examine interactions involving different classes of biomolecules on one electronic platform.

A Sensor Built Around a Molecular Wire

The core of the platform is a semiconductor chip organized as an array of sensor circuits. Think of the array as a large field of tiny listening stations: each station watches for changes in an electrical signal caused by activity at a single attached molecule.

Within each circuit element, a synthetic molecular wire bridges nanoelectrodes, which are extremely small electrical contacts. The wire is a 25-nanometer-long peptide, a short chain of amino acids, and it carries the current that the system monitors. Because the sensing component operates at molecular scale, an interaction at the probe can generate a measurable change in that current.

Programming the Target

The chip becomes useful for different biological questions through a central attachment point on the molecular wire. Researchers can connect a chosen molecular probe to that site, and the probe determines what the sensor is meant to recognize or measure.

This is similar to swapping the bait on a fishing line while keeping the same fishing rod and reel. A DNA probe can be used to look for a matching DNA sequence, while an antibody, antigen, aptamer, or enzyme can turn the same electronic architecture toward a different kind of molecular interaction. Aptamers are short nucleic-acid molecules selected to bind specific targets, functioning in some ways like synthetic antibodies.

Turning Molecular Events Into Digital Signals

The device records current over time from each sensor element at the picoampere scale. A picoampere is one trillionth of an ampere, so the chip is designed to register exceptionally small electrical changes. It converts those current-by-time measurements into digital information at 1,000 frames per second.

That rapid electronic readout lets the platform capture interaction kinetics, the timing and rate of molecular binding or enzyme activity. Instead of only reporting whether a target was present at the end of a test, the chip is intended to follow the electrical signatures of interactions as they occur in solution. Barry Merriman, PhD, Roswell Biotechnologies' chief scientific officer, said the demonstrated chip has 16,000 sensors independently monitoring the exposed solution.

Why Label-Free Measurement Is Important

Many conventional molecular assays rely on labels, such as fluorescent dyes, to make an interaction visible. Labels are often powerful tools, but attaching them can alter the molecules being studied or interfere with the interaction itself. The new platform is designed to measure parallel single-molecule interaction kinetics without labels encumbering the interacting molecules.

Jim Tour, PhD, a Rice University chemistry professor and co-author, described the goal as listening in on molecular communications. That framing reflects a central promise of the technology: biology depends on molecules binding, separating, and reacting, and an electrical sensor may provide a direct way to monitor those events at the scale where they happen.

From DNA to Enzymes

The reported system accommodates several categories of probes, including DNA, aptamers, antibodies, antigens, and enzymes. This breadth matters because molecular biology is not limited to one type of target. DNA sequence recognition, protein binding, immune interactions, and enzyme reactions all involve distinct molecules and different patterns of activity.

The team specifically identified CRISPR Cas enzymes binding target DNA sequences as a relevant application. CRISPR Cas enzymes are proteins that can recognize and act on particular DNA sequences when guided appropriately. Reading their interactions electrically could support work related to diagnostics and sequencing, while the broader platform is also positioned for drug discovery and proteomics, the study of proteins at scale.

Why This Matters

Modern molecular medicine needs measurements that are sensitive enough to distinguish individual events, fast enough to follow them over time, and practical enough to perform in large numbers. This work combines those goals in a semiconductor-based architecture rather than treating each single-molecule experiment as a separate specialized setup. The chip's 16,000-sensor design demonstrates parallelism, while its programmable probe attachment site provides flexibility.

The project also connects biosensing to a familiar technological trajectory. Semiconductor chips became widely useful because manufacturers could make increasingly dense, capable circuits at scale. Paul Mola, PhD, Roswell Biotechnologies' founder, president, and CEO, argued that molecular electronic chips could provide a similar digital foundation for biology through low-cost, all-electronic devices. The reported work establishes the sensor architecture and its ability to measure single-molecule binding kinetics and enzyme activity, while future applications will depend on how well specific assays perform for particular targets.

What Comes Next

The platform's value will rest on translating its general-purpose sensing design into useful measurements across real biological samples and applications. Its combination of a molecular wire, nanoelectrodes, programmable probes, and fast digital readout gives researchers a common electronic framework for studying many kinds of interactions. If that framework continues to scale while preserving single-molecule sensitivity, it could offer a practical route for bringing more of biology's smallest events onto a chip.

Topics: Biosensors

Start here: Biosensors explained