The first molecular electronic chip has been developed, fulfilling the 50-year goal of integrating a single molecule into a circuit to reach the ultimate extended limit of Moore’s Law. The chip, developed by Roswell Biotechnologies and a multidisciplinary team of leading academic scientists, uses a single molecule as a common sensor element in a circuit, creating a programmable biosensor.
This sensor has real-time, single-molecule sensitivity and infinite scalability of sensor pixel density.
The innovation, published this week in PNAS, will power advances in a variety of fields that are fundamentally based on observing molecular interactions, including drug discovery, diagnostics, DNA sequencing and proteomics.
“Biology works by single molecules talking to each other, but our current measurements can’t detect that,” said Jim Tour, PhD, co-author of the study, professor of chemistry at Rice and a pioneer in molecular electronics. The sensors shown here allow us to listen to these molecular communications for the first time, giving us a new and powerful view of biological information.”
The molecular electronics platform consists of a programmable semiconductor chip with an expandable sensor array structure. Each array element consists of an ammeter that monitors the current flowing through precisely-engineered molecular wires and is assembled into wide-span nanoelectrodes that are then directly coupled to the circuit. The sensor connects the desired probe molecule to a molecular wire for programming through a central engineering connection point. The observed current provides a direct, real-time electronic readout of the probe’s molecular interactions. These picoamp-level current measurements of time are read digitally from a sensor array at a rate of 1,000 frames per second, enabling molecular interaction data to be captured with high resolution, precision, and throughput.
The goal of this work is to place biosensing on top of the ideal technology for future precision medicine and personal health, adds Barry Merriman, PhD, Roswell co-founder and chief scientific officer and senior author of the paper. “This requires not only putting biosensing on a chip but using the right sensor in the right way. We have preshrunk sensor components down to the molecular level to create a biosensor platform that combines a new kind of real-time, single-molecule measurement with a long-term, unlimited roadmap for scaling up to smaller, faster, and cheaper tests and instruments.”
The new molecular electronics platform detects multiatomic molecular interactions in real time at the single molecular scale. The PNAS paper describes a broad array of probe molecules, including DNA, aptamers, antibodies and antigens, and the activity of enzymes related to diagnosis and sequencing — including the binding of the CRISPR Cas enzyme to the target DNA. It illustrates a wide range of uses for this probe, including the potential for rapid COVID testing, drug discovery, and proteomics.
The paper also describes a molecular electronic sensor that can read DNA sequences. In this sensor, DNA polymerase, the enzyme that copies DNA, is integrated into a circuit. The result is a direct electrical observation of the enzyme’s action as it copies a piece of DNA letter by letter. Unlike other sequencing techniques that rely on indirect measurements of polymerase activity, this approach allows direct, real-time observation of DNA polymerase binding nucleotides. This paper illustrates how to use machine learning algorithms to analyze these active signals to read the sequence.
“The Roswell sequencing sensor provides an entirely new, direct way to observe polymerase activity and has the potential to advance sequencing technology by an additional order of magnitude in speed and cost,” “Such ultra-scalable chips offer the possibility of highly distributed sequencing for personal health or environmental monitoring, as well as future ultra-high-throughput applications such as Exabyte-scale DNA data storage,” said Professor George Church, co-author of the paper, fellow of the National Academy of Sciences and member of roswell’s Scientific Advisory Board.