Thursday, May 19, 2022

This startup wants to kick-start a molecular electronics revival

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“It’s a great concept. I think it’s way too late for chip manufacturers to do anything for us in the life sciences,” said Nils Walter, a chemist at the University of Michigan and co-founder of aLight Sciences, a company that is also developing single molecules as biosensors, in addition to the approach is to use fluorescence, or the emission of light, instead of electrical signals to read out the results.

Roswell isn’t the only company pursuing chip-based biosensors. Dynamic Biosensors, based in Munich, for example, offers chips with DNA-based sensors 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 using modern chip-making techniques, Merriman says.

The centerpiece of Roswell’s circuitry is a molecular wire made of a chain of amino acids connected to the rest of the chip, just as a regular metal wire would be. To make a sensor, the lab attaches a molecule to the other end of the wire. When this molecule interacts with its intended target – which could be a DNA strand, an antibody, or any of a number of other biologically relevant molecules – its electrical conductivity changes. The chip registers this change and software extracts the associated interaction details.

ROSWELL BIOTECHNOLOGY

To assemble thousands of sensors, Roswell starts with a silicon chip studded with prefabricated nanoelectrodes and then uses electrical voltage to pull molecules out of the 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.

Roswell’s approach could revive some of the hope molecular electronics researchers had 20 years ago. At the time, it seemed that the small size of molecules could help make circuit components smaller and computer chips denser. Intriguingly, a molecular chipmaker could basically “assemble” circuits, adding molecules under highly controlled conditions and having them assemble into desired structures all by themselves, explains George Church, a Harvard geneticist and member of the Roswell Scientific Advisory Board. †

Excitement over such molecular properties led to a rapid growth of the molecular electronics field in the late 1990s. It seemed the perfect time. “There were all these predictions in the ’80s and ’90s, about how silicon would hit a brick wall,” Tour recalls. But it didn’t; engineers just kept going. “We didn’t shoot a static target. Silicon kept performing better,” he says. Philip Collins, a physicist at the University of California, Irvine, who has previously consulted for Roswell, says the ensuing demise of molecular electronics was quite dramatic: “I’d say nine of the ten researchers dropped out.”

With the new chip, Roswell is instead targeting an application for which silicon is not suitable. Molecules are special because “they can be so much more complex than binary,” Collins says. “They can encode all these interesting different states, like in biochemistry, which we just don’t have any other ways to access.”

The new vision, shared by Roswell and other on-chip molecular tech makers, is of biosensors that allow people to monitor biomarkers such as vitamin levels or evidence of infection with just a little more effort than it currently takes to monitor their hearts. rate on a smartwatch. In Roswell’s case, thousands of biosensors could simultaneously detect different molecular interactions, and the chips would be disposable.

Walter of the University of Michigan notes that while Roswell’s device can hold more than 10,000 biosensors on a single chip, with hundreds of thousands or millions more, it would push the device toward more marketable functionality, especially when it comes to the detecting low concentrations of biomarkers in early disease.

Mola and Merriman
Roswell’s CEO, Paul Mola (left) and Barry Merriman, CSO and co-founder.

ROSWELL BIOTECHNOLOGY

The commercial biotechnology market is not a new arena for Church, Merriman and other business leaders. But the Roswell team’s experience and expertise haven’t made the company’s financing journey as easy as CEO Paul Mola once hoped. After the company’s paper in January, Mola says, he expected venture capital to pour in, but it didn’t. Although Roswell has raised more than $60 million to date, mostly from strategic investors and representatives of wealthy families, it had to cut its workforce nearly in half in February.

Mola is frustrated by the lack of investment in the company when, he says, it is so close to commercialization. “We feel like we’ve really done a lot with so little,” he says. “Now we really need the community to stand up and support us and help us all the way.”

Mola, who is Black, says part of the problem lies in the biotech industry’s tricky track record on diversity.a concern Stat reported beginning of March. “If you think of entrepreneurs and founders, they have generally had an entrepreneur in their family, they have access to networks and investors. From a systemic and fundamental point of view, black founders don’t have that,” he says. “I do not have that.”

Roswell is still on track to release a commercial device by the end of the year, Mola says. The startup is about to begin its next funding streak. It also introduces a service that could attract customers before it’s possible to sell chips directly to them: scientists can now send samples to Roswell and run its molecular biosensors in-house, collecting valuable data on, for example, the real-time feature. of new drugs.

For Tour, Roswell’s work remains a symbol of the molecular electronics renaissance: “It’s nice to see something happen and be able to say, OK, it worked, it just took us longer than we thought.”

Karmela Padavic-Callaghan is a freelance journalist based in Brooklyn, New York.

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