Membrane-on-a-chip automates Covid-19 drug testing

Membrane-on-a-chip automates Covid-19 drug testing

Technology News |
By Nick Flaherty

Researchers have developed a ‘membrane on a chip’ that allows continuous monitoring of how drugs and infectious agents interact with human cells, bacteria and viruses. The technology is being adapted to test potential drug candidates for Covid-19.

The researchers from the University of Cambridge, Cornell University and Stanford University, say the chip can mimic any type of cell, including the Covid-19 virus. 

The key is that the cell membrane is grown while preservinges all of the critical aspects, such as structure, fluidity and control over ion movement, without having to keep a cell alive. This also makes it much safer to test out drugs on the membrane of the SARS-CoV-2 virus without having to use the virus itself.

The cell-sized chip integrates a cell membrane with conducting polymer electrodes and transistors. Mutlitple devices can be combined in an array.

To generate the on-chip membranes, the Cornell team first optimised a process to produce membranes from live cells and then, working with the Cambridge team, coaxed them onto polymeric electrodes in a way that preserved all the functionality. The hydrated conducting polymers provide a more ‘natural’ environment for cell membranes and allows robust monitoring of membrane function.

The Stanford team optimised the polymeric electrodes for monitoring changes in the membranes. The device no longer relies on live cells that are often technically challenging to keep alive and require significant attention, and measurements can last over an extended time period.

The chip has been used to monitor the activity of ion channels, a class of protein in human cells which are the target of more than 60 per cent of approved drugs. The results are published in two recent papers in Langmuir and ACS Nano.

“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, associate professor of chemical and biomolecular engineering at Cornell and senior author of the Langmuir paper.

“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, and senior author of the ACS Nano paper. “This method is compatible with high-throughput screening and would reduce the number of false positives making it through into the R&D pipeline.”

“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,” said Dr Anna-Maria Pappa, also from Cambridge and joint first author on both papers.

The research is supported by funding from the United States Defense Research Projects Agency (DARPA) to demonstrate how viruses such as influenza interact with cells. Now, DARPA has provided additional funding to test the device’s effectiveness in screening for potential drug candidates for Covid-19 in a safe and effective way.

The team will focus on making virus membranes that don’t contain the viral nucleic acid and fusing those with the chips. This will allow new drugs or antibodies that neutralise the virus spikes to  gain entry into the host cell to be identified. This work is expected to get underway on 1 August.

“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, Cornell researcher and joint first author on both papers.

Future work will focus on scaling up production of the devices at Stanford and automating the integration of the membranes with the chips, using the fluidics expertise from Stanford PI Juan Santiago who will join the team in August.

“This project has merged ideas and concepts from laboratories in the UK, California and New York, and shown a device that works reproducibly in all three sites. It is a great example of the power of integrating biology and materials science in addressing global problems,” said Stanford lead PI Professor Alberto Salleo.;

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