In the biotech and pharmaceutical industries, ELISA tests provide critical quality control during drug development and manufacturing. The tests can precisely quantify protein levels, but they also require hours of work by trained technicians and specialized equipment. That makes them prohibitively expensive, driving up the costs of drugs and putting research testing out of reach for many.
Now the Advanced Silicon Group (ASG), founded by Marcie Black '94, MEng '95, PhD '03 and Bill Rever, is commercializing a new technology that could dramatically lower the time and costs associated with protein sensing. ASG's proprietary sensor combines silicon nanowires with antibodies that can bind to different proteins to create a highly sensitive measurement of their concentration in a given solution.
The tests can measure the concentration of many different proteins and other molecules at once, with results typically available in less than 15 minutes. Users simply place a tiny amount of solution on the sensor, rinse the sensor, and then insert it into ASG's handheld testing system.
"We're making it 15 times faster and 15 times lower cost to test for proteins," Black says. "That's on the drug development side. This could also make the manufacturing of drugs significantly faster and more cost-effective. It could revolutionize how we create drugs in this country and around the world."
Since developing its sensor, ASG's team has received inquiries from a long list of people interested in using them to develop new therapeutics, help elite athletes train, and understand soil concentrations in agriculture, among other applications.
For now, though, the small company is focusing on lowering barriers in health care by selling its low-cost sensors to companies developing and manufacturing drugs.
"Right now, money is a limiting factor in researching and creating new drugs," explains Marissa Gillis, a member of ASG's team. "Making these processes faster and less costly could dramatically increase the amount of biologic testing and creation. It also makes it more viable for companies to develop drugs for rare conditions with smaller markets."
A family away from home
Black grew up in a small town in Ohio before coming to MIT for three degrees in electrical engineering.
"Going to MIT changed my life," Black says. "It opened my eyes to the possibilities of doing science and engineering to make the world a better place. Also, just being around so many amazing people taught me how to dream big."
For her PhD, Black worked with the late Institute Professor Mildred Dresselhaus, a highly acclaimed physicist and nanotechnology pioneer who Black remembers for her mentorship and compassion as much as her contributions to our understanding of exotic materials. Black couldn't always afford to go home for holidays, so she'd spend Thanksgivings with the Dresselhaus family.
"Millie was an amazing person, and her family was a family away from home for me," Black says. "Millie continued to be my mentor - and I hear she did this with a lot of students - until the day she died."
For her thesis, Black studied the optical properties of nanowires, which taught her about the nanostructures and optoelectronics she'd eventually use as part of the Advanced Silicon Group.
Following graduation, Black worked at the Los Alamos National Laboratory before founding the company Bandgap Engineering, which developed efficient, low-cost nanostructured solar cells. That technology was subsequently commercialized by other companies and became the subject of a patent dispute. In 2015, Black spun out the Advanced Silicon Group to apply a similar technology to protein sensing.
ASG's sensors combine known approaches for sensitizing silicon to biological molecules, using the photoelectric properties of silicon nanowires to detect proteins electrically.
"It's basically a solar cell that we functionalize with an antibody that's specific to a certain protein," Black says. "When the protein gets close, it brings an electrical charge with it that will repel light carriers inside the silicon, and doing that changes how well the electron and the holes can recombine. By looking at the photocurrent when you're exposed to a solution, you can tell how much protein is bound to the surface and thus the concentration of that protein."
ASG was accepted into MIT.nano's START.nano startup accelerator and MIT's Office of Corporate Relations Startup Exchange Program soon after its founding, which gave Black's team access to cutting-edge equipment at MIT and connected her with potential investors and partners.
Black has also received broad support from MIT's Venture Mentoring Service and worked with researchers from MIT's Microsystems Technology Laboratories (MTL), where she conducted research as a student.
"Even though the company is in Lowell, [Massachusetts], I'm constantly going to MIT and getting help from professors and researchers at MIT," Black says.
Biosensing for impact
From extensive discussions with people in the pharmaceutical industry, Black learned about the need for a more affordable protein-measurement tool. During drug development and manufacturing, protein levels must be measured to detect problems such as contamination from host cell proteins, which can be fatal to patients even at very low quantities.
"It can cost more than $1 billion to develop a drug," Black says. "A big part of the process is bioprocessing, and 50 to 80 percent of bioprocessing is dedicated to purifying these unwanted proteins. That challenge leads to drugs being more expensive and taking longer to get to market."
ASG has since worked with researchers to develop tests for biomarkers associated with lung cancer and dormant tuberculosis and has received multiple grants from the National Science Foundation, the National Institute of Standards and Technology, and the commonwealth of Massachusetts, including funding to develop tests for host cell proteins.
This year, ASG announced a partnership with Axogen to help the regenerative nerve repair company grow nerve tissue.
"There's a lot of interest in using our sensor for applications in regenerative medicine," Black says. "Another example we envision is if you're sick in rural India and there's no doctor nearby, you can show up at a clinic, nurses can give this to you and test for the flu, Covid-19, food poisoning, pregnancy, and 10 other things all at once. The results come in 15 minutes, then you could get what you need or teleconference a doctor."
ASG is currently able to produce about 2,000 of its sensors on 8-inch chips per production line in its partner's semiconductor foundry. As the company continues scaling up production, Black is hopeful the sensors will lower costs at every step between drug developers and patients.
"We really want to lower the barriers for testing so that everyone has access to good health care," Black says. "Beyond that, there are so many applications for protein sensing. It's really where the rubber hits the road in biology, agriculture, diagnostics. We're excited to partner with leaders in every one of these industries."
