First Molecular Electronics Chip Developed – Realizes 50-Year-Old Goal

The Roswell Molecular Electronics chip uses individual molecules as universal sensor elements in the chain to create a programmable biosensor with one-molecular-time real-time sensitivity and unlimited scalability of sensor pixel density. Credit: Roswell

A platform for single-molecular measurement of binding kinetics and enzyme activity.

The first molecular electronics chip was developed, which realizes the 50-year goal of integrating individual molecules into circuits to achieve the ultimate scaling limits of Moore’s Law. Developed by Roswell Biotechnologies and an interdisciplinary team of leading scientists, the chip uses individual molecules as universal sensor elements in a circuit to create a programmable biosensor with molecular sensitivity in real time and unlimited scalability in pixel density. This is an innovation that appeared this week in a peer-reviewed article Proceedings of the National Academy of Sciences (PNAS)will contribute to advances in a variety of fields that are largely based on monitoring molecular interactions, including drug discovery, diagnosis,[{” attribute=””>ДНК паслядоўнасць і пратэёміка.

«Біялогія працуе, калі адзінкавыя малекулы размаўляюць адзін з адным, але нашы існуючыя метады вымярэння не могуць гэтага выявіць», – сказаў суаўтар Джым Тур, доктар філасофіі, прафесар хіміі Універсітэта Райса і піянер у галіне малекулярнай электронікі. «Датчыкі, прадэманстраваныя ў гэтым артыкуле, упершыню дазволілі нам праслухаць гэтыя малекулярныя сувязі, што дазваляе атрымаць новы і магутны погляд на біялагічную інфармацыю».

The molecular electronics platform consists of a programmable semiconductor chip with a scalable sensor array architecture. Each element of the array consists of an electric current meter that monitors the current flowing through a precise molecular wire assembled to cover the nanoelectrodes that connect it directly to the circuit. The sensor is programmed by attaching the desired probe molecule to the molecular wire through a centrally designed conjugation site. The observed current provides direct electronic reading of the molecular interactions of the probe in real time. These current measurements in picoamperes are read from an array of sensors digitally at 1000 frames per second to obtain molecular interaction data with high resolution, accuracy and throughput.

“The aim of this work is to put bio-research on an ideal technological basis for the future of precision medicine and personal health,” added co-founder and lead researcher Barry Merriman, Ph.D., senior author. “This requires not only incorporating bioassay on the chip, but also in the right order, with the right sensor. We have previously reduced the sensor element to the molecular level to create a biosensory platform that combines a whole new way of measuring a single molecule in real time with a long-term, unlimited scaling roadmap for smaller, faster and cheaper tests and tools. ”

The new molecular electronics platform detects multi-atomic molecular interactions on a single molecule scale in real time. The PNAS paper presents a wide range of probe molecules, including DNA, aptomers, antibodies, and antigens, as well as the activity of enzymes involved in diagnosis and sequencing, including the CRISPR Cas enzyme, which binds its target DNA. It illustrates the wide range of applications of such probes, including the ability to rapidly test for COVID, drug detection, and proteomics.

The article also presents a molecular electronics sensor capable of reading DNA sequences. In this sensor, DNA polymerase, an enzyme that copies DNA, is integrated into the chain, and the result is direct electrical observation of the action of this enzyme as it copies a fragment of DNA, letter by letter. Unlike other sequencing technologies that rely on indirect measurements of polymerase activity, this approach provides direct real-time monitoring of a DNA polymerase enzyme that includes nucleotides. The paper illustrates how these activity signals can be analyzed using machine learning algorithms so that the sequence can be read.

“The Roswell Sequencing Sensor provides a new direct look at polymerase activity with the potential to advance sequencing technology by additional orders of magnitude in speed and cost,” said Professor George Church, co-author of the work, a member of the National Association. Academy of Sciences and member of the Roswell Scientific Advisory Board. “This ultra-scalable chip opens up the possibility of widespread sequencing for personal health or environmental monitoring, as well as for future ultra-high-bandwidth applications such as DNA storage on an exobyte scale.”

Reference: “Molecular Electronics Sensors on a Scalable Semiconductor Chip: A Platform for Measuring Single Molecule Binding Kinetics and Enzyme Activity” by Karl W. Fuller, Pius S. Padayati, Hadi Abderachim, Lisa Adamiak, Nolan Alagar, Naharaja Dharajah Anantapad Chulmin Choi, Kevin J. Delaney, Rich Dubelzig, Julie Francanetz, Chris Garcia, Calvin Gardner, Daniel Gebhardt, Tim Geiser, Zachary Gutierrez, Drew A. Hall, Andrew P. Hodges, Guang Yuan Hou, Sonal Jain, Teresa Jones, Rayland Lobanet, Raymond Lobton , Pratik Mohan, Paul Mole II, Paul Mudonda, James Mallinix, Tuan Nguyen, Frederick Olinger, Sarah Orr, Yusuan Wyang, Paul Pan, Namsok Park, David Poros, Keshav Prabhu Reese, Travers Reuel, Trevor Ruer, Trevor Sauerbry, Jamie R. Prem Sinha, Jackie Tu, A. G. Wenkatesh, Sushmita Vijay Kumar, Le Zheng, Sunho Jin, James M. Tour, George M. Church, Paul W. Mola and Barry Merriman, January 24, 2022, Proceedings of the National Academy of Sciences.
DOI: 10.1073 / pnas.2112812119

About Roswell Biotechnologies

Roswell Biotechnologies digitizes biology using molecular electronics to predict, prevent and treat disease. The company has developed the world’s first molecular electronics chip, Roswell ME Chip ™, which integrates individual molecules into standard semiconductor chip technology to deliver a programmable biosensor that integrates a wide range of bioassay and measurement applications on a single platform. The Roswell ME platform is commercialized for applications in drug research and discovery, molecular diagnostics, sequencing, and storage of digital DNA data. Roswell Biotechnologies was founded in 2014 by industry leaders in genomic technology and is headquartered in San Diego, California.

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