New Sensor Chip Can Track the Activity of a Single Molecule — and Scale Its Resolution Upwards

A team of scientists, working with Roswell Biotechnologies, claims to have created the world's first single-molecule sensor chips scalable to unlimited resolutions — creating programmable biosensors, which work on observation of molecular interactions.

"Biology works by single molecules talking to each other, but our existing measurement methods cannot detect this," explains paper co-author Jim Tour, PhD, and professor at Rice University of the team's work. "The sensors demonstrated in this paper for the first time let us listen in on these molecular communications, enabling a new and powerful view of biological information."

"The goal of this work is to put biosensing on an ideal technology foundation for the future of precision medicine and personal wellness," claims Roswell co-founder and chief scientific officer Barry Merriman, PhD, the paper's senior author. "This requires not only putting biosensing on chip, but in the right way, with the right kind of sensor. We've pre-shrunk the sensor element to the molecular level to create a biosensor platform that combines an entirely new kind of real-time, single-molecule measurement with a long-term, unlimited scaling roadmap for smaller, faster and cheaper tests and instruments."

What the team claims to have developed is a modular platform that includes a programmable semiconductor chip with a fully-scalable sensor array based around monitoring current flow through a molecular wire spanning nanoelectrodes connecting it to the circuit. A "probe molecule" is connected to the molecular wire, then the system provides a real-time electronic readout of molecular interactions at the site of the probe - at a rate of 1,000 readings per second.

Capable of sensing interactions at the scale of a single molecule, the platform has already been tested with a wide range of probe molecules including DNA, antibodies, antigens, aptamers, and a probe capable of monitoring a CRISPR Cas enzyme binding its target DNA. One demonstration even used a probe with integrated DNA polymerase to observe enzymatic activity as DNA is copied letter by letter — using machine learning to process the data and read the resulting sequence.

"The Roswell sequencing sensor provides a new, direct view of polymerase activity, with the potential to advance sequencing technology by additional orders of magnitude in speed and cost," claims co-author George Church, professor, of the work. "This ultra scalable chip opens up the possibility for highly distributed sequencing for personal health or environmental monitoring, and for future ultra-high throughput applications such as Exabyte-scale DNA data storage."

The team's work has been published under open-access terms in the Proceedings of the National Academy of Sciences (PNAS).