Cell “membrane-on-chip” helps test potential drug candidates for COVID-19

Researchers have developed a human cell “membrane-on-a-chip” that can continuously monitor how drugs and infectious agents interact with our cells.

Researchers at the University of Cambridge, Cornell University, and Stanford University say their devices can mimic any type of cell, including the robust cell walls of bacteria, humans, or plants.

Their work recently focused on how COVID-19 attacks human cell membranes and, more importantly, how COVID-19 can block it.

These devices are used to monitor the activity of the ion channel, a protein class of human cells that is formed on the chip while maintaining the orientation and function of the cell membrane and is the target of over 60% of approved drugs. I am.

The results are published in two recent papers: Langmuir And ACS Nano..

The cell membrane plays a central role in biological signal transduction, controlling everything from pain relief to viral infection, and acts as a gatekeeper between the cell and the outside world.

The team set out to create a sensor that preserves all the important aspects of the cell membrane—regulation of structure, fluidity, and ionic movement—without the time-consuming steps required for cell survival.

The device uses an electronic chip to measure changes in the upper membrane extracted from cells, allowing scientists to safely and easily understand how cells interact with the outside world.

The device integrates cell membranes with conducting polymer electrodes and transistors.

To produce on-chip membranes, Cornell team first optimized the process of producing membranes from living cells and then worked with the Cambridge team to coax them into polymer electrodes in a way that preserves all functionality. Did.

The hydrated conductive polymer provides a more natural environment for cell membranes, allowing robust monitoring of membrane function.

The Stanford team has optimized polymer electrodes to monitor membrane changes. This device is technically difficult to stay alive, relies on live cells that require considerable attention, and measurements can be continued for long periods of time.

Membranes are made from human cells, so it’s like taking a biopsy of the surface of those cells-we have all the materials present, such as proteins and lipids, but when using live cells There are no challenges. “

Susan Daniel, Senior Researcher and Associate Professor, Department of Chemistry and Biomolecular Engineering, Cornell University

“This type of screening is usually done in the pharmaceutical industry with live cells, but our device offers a simpler alternative,” said Dr. Cambridge in Chemical Engineering and Biotechnology. ACS Nano paper.

“This method is compatible with high throughput screening and reduces the number of false positives that reach the R&D pipeline.”

“The device is as small as a human cell size and can be easily assembled into an array, allowing us to make multiple measurements simultaneously,” says Anna-Maria Pappa from Cambridge. Also mentioned by Cambridge and co-lead authors. ..

To date, the purpose of this study, funded by the US Defense Research Projects Agency (DARPA), has been to demonstrate how viruses such as influenza interact with cells.

Currently, DARPA is providing additional funding to test the effectiveness of the device in screening potential drug candidates for COVID-19 in a safe and effective manner.

Given the significant risks associated with researchers working on the virus that causes COVID-19, SARS-CoV-2, the project scientists will focus on viral membrane production and chip fusion.

The viral membrane is the same as the SARS-CoV-2 membrane, but it does not contain viral nucleic acid.

In this way, new drugs or antibodies to neutralize the viral spike used to gain entry into the host cell can be identified. This work will begin on August 1.

“With this device, we are not exposed to a dangerous working environment to fight SARS-CoV-2. This device speeds the screening of drug candidates and shows how this virus works. We will provide answers to your questions,” said Dr. Han-Yuan Liu. Co-leader of both papers with Cornell researchers.

Future work will focus on expanding device production at Stanford and automating the integration of membranes and chips, leveraging fluid engineering expertise from Stanford PI Fan Santiago to join the team in August.

“This project has integrated ideas and concepts from laboratories in the United Kingdom, California, and New York to show devices that work reproducibly at all three sites.

This is a great example of the power of integrating biology and materials science in tackling global issues,” said Stanford Principal Investigator Professor Alberto Saleo.