Cell ‘Membrane on a Chip’ Developed for Screening of Coronavirus Drug Candidates

Scientists involved in developing drugs for treatments and therapies always look at how they can best target the threat directly. In the midst of finding a cure for the coronavirus, a team from three universities and two studies developed a human cell "membrane on a chip" so they can keep track of how infections and cells interact. This could be a breakthrough in finding a cure for the coronavirus.

Cell membranes have two primary functions: acting as a barrier that blocks undesirable substances out while becoming a gateway for essential nutrients coming in as waste products exit the cell. This is disrupted when a virus or bacteria chooses the cell to be a host, penetrating the membrane and multiplying harmful, infected cells.

Researchers from the University of Cambridge, Cornell University, and Stanford University developed a device that mimics the cells of humans, bacteria, and plant membranes. Their technology allowed them to observe how the SARS-CoV-2 spike protein--which causes COVID-19--penetrates human cells upon infection, and how the immune system can potentially block it.

A Membrane on a Chip

The device consists of an electronic chip that contains ion channel activity, or proteins responsible for the development of 60% pharmaceutical-approved targeting drugs. The membrane on a chip is then measured for any changes in the cell surface as it interacts with a simulation of a virus or other external molecules.

A sensor was created to electronically measure how the cell membrane functions in real life--its structure, fluidity, and management of ion movement. Membrane biological signals were continuously observed without the scientists keeping cells alive in maintained environments like other cell research done in laboratory dishes.

Because the membranes are produced from human cells, it's like having a biopsy of that cell's surface--"We have all the material that would be present including proteins and lipids, but none of the challenges of using live cells," said Dr. Susan Daniel, a chemical and biomolecular engineering associate professor at Cornell.

'Screening of Drug Candidates'

The Cornell team created membranes from live cells then the Cambridge team transferred them onto hydrated polymeric electrodes, or the chips, which preserved all their organic or native functions. Next, the Stanford scientists optimized the polymeric electrodes to no longer rely on live cells so that they can monitor changes in the behavior of the membrane over time.

"This type of screening is typically done by the pharmaceutical industry with live cells, but our device provides an easier alternative," said Dr. Róisín Owens from Cambridge's Department of Chemical Engineering and Biotechnology. "This method is compatible with high-throughput screening and would reduce the number of false positives making it through into the R&D pipeline."

Dr. Anna-Maria Pappa from Cambridge added, "the device can be as small as the size of a human cell and easily fabricated in arrays, which allows us to perform multiple measurements at the same time." With the support of the United States Defense Research Projects Agency (DARPA), the team is observing how cell membranes interact with the influenza virus.

Soon, they will be using the device to screen potential drug candidates for coronavirus in a safer and more effective way than human trials.

"With this device, we are not exposed to risky working environments for combating SARS-CoV-2. The device will speed up the screening of drug candidates and provide answers to questions about how this virus works," said Dr. Han-Yuan Liu, a researcher from Cornell.

Stanford Professor Alberto Salleo added that the device is a "great example of the power of integrating biology and materials science in addressing global problems."