Paul van Gerven
8 February

The US company Roswell Biotechnologies has wired single molecules into standard CMOS circuitry, creating what it calls the world’s first molecular electronics chip.

For centuries, chemistry has been about observing and manipulating the collective behavior of molecules. It wasn’t until the 1980s that researchers were handed the first tools to peek at and prod individual molecules. The number of available tools has greatly increased since then, and many of those have been gratefully adopted by life scientists to study the underpinnings of life at the molecular level.

And yet, there’s much left to be desired. Studies into the interactions between biomolecules are often still about averages: the extracted information is typically an average of many interaction events between molecules, obtained on a timescale much longer than the events themselves. In addition, these predominantly optical methods are constrained by the signal-to-noise ratio, spatial resolution and bandwidth. Only highly specialized experiments can unveil the nanoworld in real-time. These approaches are unsuitable for routine adoption in the life sciences.

Not only can all-electronic measurements remove some of the current constraints, but their intrinsic compatibility with standard chip technology also offers great potential for low-cost, high-speed and miniaturizable sensor technology. Roswell Biotechnologies claims to have achieved just that. By wiring single molecules into CMOS circuitry, the San Diego-based company has created what it calls the world’s first molecular electronics chips. Apart from studying biomolecular processes in real-time, these devices can also be used for diagnosing diseases, testing drug candidates, DNA sequencing and other biomolecular applications – all at unprecedented speed.

Roswell molecular electronics
Credit: Roswell Biotechnologies

Off-chip

Integrating single molecules into electronic circuits has been a decades-old dream. As early as 1974, IBM researchers proposed that individual molecules could be turned into electronic components. The first single-molecule circuits were demonstrated in the 1990s, after which the number of publications on the subject exploded. There has been considerable commercial interest as well, particularly in using carbon nanotubes in logic and memory chips. It’s still unclear, however, when – or if – this research will move out of the lab and into the fab.

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Roswell’s sensing technology is also still in the R&D stage. The sensor element is a molecular wire spanning a 20-nanometer gap between electrodes. To this ‘bridge’ a probe molecule is anchored. Whenever this ‘hook’ catches something, a change in resistance is induced, resulting in an observable change in the picoampere current that’s pulsed through the molecular wire.

A single chip contains 16,000 of these sensors, along with the 180μm CMOS circuitry needed to digitize and transfer sensor readings off-chip, at a rate of 1,000 frames per second. Eventually, Roswell expects to scale up to millions of ‘pixels’ per chip. The biotech company also supplies instrumentation for data processing and visualization in different settings, such as laboratories, doctors’ offices and possibly even at home.

Guilty

Roswell has demonstrated the validity and versatility of its sensor platform in a range of different applications. In one experiment that’s particularly relevant today, the researchers performed the last step of a corona PCR test, ie testing whether a piece of SARS-CoV-2 genetic code is present. Crucially, however, they showed that – thanks to the power of single-molecule sensitivity – it wasn’t necessary to purify the PCR sample from ‘background’ genetic material. The ability to work with crude samples facilitates testing procedures and may even lead to PCR self-testing (PCR tests are significantly more sensitive and specific than the rapid antigen lateral flow tests currently used for testing at home).

The sensor chip, along with the PCR test and other examples of biosensing measurements, has recently been described in Proceedings of the National Academy of Sciences (PNAS), a high-impact peer-reviewed journal. By doing so, Roswell hopes to convince the world that its technology is sound. There certainly is plenty of skepticism to overcome after Theranos, another Californian high-flying biotech company promising to revolutionize diagnostic tests, came crashing down. Theranos’ founder Elizabeth Holmes has recently been found guilty on four counts of fraud.