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“It’s a great concept. I think chipmakers should do something for us in biosciences a long time ago,” says Nils Walter, a chemist at the University of Michigan and co-founder of aLight Sciences, a company that is also developing single-molecule biosensors, except their approach. is to use fluorescence, or the emission of light, instead of electrical signals to read the results.
Roswell isn’t the only company looking at chip-based biosensors. For example, Munich-based Dynamic Biosensors offers DNA-based sensor chips that use light. But Roswell’s manufacturing approach produces precise sensors that are flexible enough to envision a “universal biosensor” that can be mass-produced with modern chip-making techniques, says Merriman.
The centerpiece of the Roswell circuitry is a molecular wire made of a chain of amino acids that is connected to the rest of the chip like a regular metal wire would be. To create a sensor, the lab attaches a molecule to the other end of the wire. When this molecule interacts with its intended target, which may be a DNA strand, an antibody, or any other biologically relevant molecule, its electrical conductivity changes. The chip registers this change and the software extracts the corresponding interaction details.
To assemble thousands of sensors, Roswell starts with a silicon chip studded with prefabricated nanoelectrodes, then uses electrical voltage to pull molecules out of solution and onto the chip. This part of the mounting process takes less than 10 seconds; in the past, similar molecular processes took hours or even days.
The Roswell approach could revive some of the hopes molecular electronics researchers had 20 years ago. At the time, it seemed that the small size of molecules might help make circuit components smaller and computer chips denser. Interestingly, a molecular chipmaker could, in principle, “self-assemble” circuits, adding molecules under highly controlled conditions and letting them assemble into desired structures on their own, explains George Church, a Harvard geneticist and a member of the scientific advisory board of Roswell. .
The enthusiasm for such molecular properties led to a rapid growth in the field of molecular electronics in the late 1990s. It seemed like the perfect time. “There were all these predictions throughout the ’80s and ’90s about how silicon was going to hit a brick wall,” recalls Tour. But it was not like that; the engineers moved on. “We weren’t shooting at a static target. Silicon kept getting better,” he says. Philip Collins, a physicist at the University of California, Irvine, who was previously a Roswell consultant, says the resulting drop in molecular electronics was quite dramatic: “I’d say nine out of 10 researchers dropped out.”
With the new chip, Roswell is targeting an application for which silicon is not suitable. Molecules are special because “they can be much more complex than binaries,” says Collins. “They can encode all these different interesting states, like in biochemistry, that we just don’t have other ways to access.”
The new vision, shared by Roswell and other molecular-on-chip technology makers, is for biosensors that would allow people to check biomarkers like vitamin levels or evidence of an infection with just a little more hassle than it now takes to check. your heart. rate on a smart watch. In the case of Roswell, thousands of biosensors could detect different molecular interactions simultaneously, and the chips would be disposable.
Walter of the University of Michigan points out that while the Roswell device can accommodate more than 10,000 biosensors on a chip, having hundreds of thousands or millions would push the device toward more marketable functionality, especially when it comes to detecting low concentrations of biomarkers in early stages. disease.
The commercial biotech market is not a new arena for Church, Merriman and other business leaders. But the experience and expertise of the Roswell team have not made the process of financing the company as easy as CEO Paul Mola had hoped. After the company newspaper in January, Mola says, he expected venture capital to come in, but it didn’t. Although Roswell has raised more than $60 million so far, mostly from strategic investors and representatives of wealthy families, it had to cut its workforce by nearly half in February.
Mola is frustrated by the lack of investment in the company when it is, he says, so close to commercialization. “We feel like we’ve actually done a lot with so little,” he says. “Now we really need the community to step up and stand behind us and see us through to the end.”
Mola, who is black, says part of the problem lies in the biotech industry’s troubled history with diversity, a concern Stat reported in early March. “If you think about entrepreneurs and founders, they generally have had an entrepreneur in their family, they have networks and access to investors. From a systemic and fundamental standpoint, Black founders don’t have that,” she says. “I do not have that”.
Roswell is still on track to release a commercial device by the end of the year, says Mola. The startup is about to start its next funding series. It’s also introducing a service that may lure customers in before it’s possible to sell them chips directly: Scientists will now be able to ship samples to Roswell and have their molecular biosensors work on them internally, collecting valuable data on, say, the function in real time of new medicines.
For Tour, the Roswell work remains a symbol of the renaissance of molecular electronics: “It’s nice to be able to see something happen and say, okay, it worked, it just took longer than we thought.”
Karmela Padavic-Callaghan is a freelance journalist based in Brooklyn, New York.