Software and microelectronics fabrication techniques let research identify powerful immune cells

Photo: IsoPlexis
A Different Chip: IsoPlexis uses microelectronics fabrication techniques and software analytics to simultaneously study thousands of immune cells.

Cancer patients’ bodies contain immune cells that, through successful immunotherapy, can deliver proteins to destroy tumors. But it had been difficult in the past to identify which immune cells were the most powerful.

Now, IsoPlexis, a life sciences startup based in Connecticut, has created “microchips” that quickly identify 42 proteins emitted from thousands of individual cells. Software then analyzes the results to determine which cells are the highly potent “Superman” cells that are the most effective in immunotherapy.

In biology, “to understand the complete picture, you have to look at thousands of cells,” says Rong Fan, IsoPlexis cofounder.

Fan developed the underlying science while a postdoc at Caltech working with chemistry professor James R. Heath, who is also director of the National Cancer Institute’s NSB Cancer Center.

When Fan, associate professor of biomedical engineering at Yale, came to New Haven, he met Sean Mackay, who was finishing up his MBA. Mackay says he was looking to partner with someone working in life sciences because he had seen the impact that early-stage life sciences firms could have on people’s lives.

The timing of the company’s founding coincided with a boom in the use of immuno-oncology treatment. IsoPlexis received early funding from Spring Mountain Capital, Connecticut Innovations, Yale, the National Institutes of Health’s Small Business Innovation Research grant, and venture capital investors.

Still, the startup had to convince its potential customers that it offered benefits over existing technology. “We never thought our goal would be to dethrone existing technology, but rather be a complement to them,” says cofounder and CEO Mackay. IsoPlexis’s microchips use microelectronics fabrication technology to trap single cells in a microchamber and isolate them from one another, says Heath, now director of IsoPlexis’s scientific advisory board. One of the company’s major inventions is the technique to parallelize and squeeze microsensor detection pads into the tiny microchambers, each with a volume of about a nanoliter.

At the chip’s proof-of-concept phase, it took a week to manually count the cells and analyze the data. IsoPlexis hired Patrick Paczkowski as vice president of software to turn the company’s data-processing and bioinformatics software into a fully automated commercial product. Like Mackay, Paczkowski had a degree that had nothing to do with biology, but he wanted to create better algorithms to analyze the cells. This and other engineering efforts led to the IsoLight system, which can complete automated image processing and data-quantification analytics in a few hours.

The technology is not limited to oncology. The company began working in that field partly based on the founders’ research focus and because funding for cancer research is more plentiful than for other diseases. Mackay says the technology can be used for research, and eventually diagnostics, for autoimmune diseases such as multiple sclerosis, systemic lupus, Crohn’s disease, and Alzheimer’s disease. Scientists are also researching applying the technology to immunotherapy for infectious diseases, such as Lyme, and to vaccine development.

Michael Andreeff, M.D., a genetics professor at the University of Texas MD Anderson Cancer Center and a pioneer in flow cytometry—the measurement of single-cell characteristics—called the IsoPlexis “a very elegant system.” He added that he was able to uncover some surprising results using the technology in his lab: “Importantly, the IsoPlexis system may be able to predict what patients will respond to immune-checkpoint inhibitors.”

While the process is not revolutionary, Andreeff said that if these results are confirmed, the IsoPlexis could be a 9+ on a 10-point scale as a research tool. “No other technology has provided this kind of prediction,” he said. Asked whether he had a financial stake in IsoPlexis, Andreeff said, “I wish.”

are confirmed, the IsoPlexis could be a 9+ on a 10-point scale as a research tool. “No other technology has provided this kind of prediction,” he said. Asked whether he had a financial stake in IsoPlexis, Andreeff said, “I wish.”


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