A new human cell ”membrane on a chip” allows continuous monitoring of how drugs and infectious agents interact with our cells, an advance that may be employed to test potential drug candidates for COVID-19, scientists said on Monday. According to the researchers from the University of Cambridge in the UK, Cornell University and Stanford University in the US, the device could mimic any cell type — bacterial, human or even the tough cells walls of plants. The devices have been formed on chips while preserving the orientation and functionality of the cell membrane, according to the results published in two papers in journals Langmuir and ACS Nano. They have been successfully 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 pharmaceuticals, the researchers said. Cell membranes play a central role in biological signalling, controlling everything from pain relief to infection by a virus, acting as the gatekeeper between a cell and the outside world, they said. The team set out to create a sensor that preserves all of the critical aspects of a cell membrane — structure, fluidity, and control over ion movement — without the time-consuming steps needed to keep a cell alive. The device uses an electronic chip to measure any changes in an overlying membrane extracted from a cell, enabling the scientists to safely and easily understand how the cell interacts with the outside world. It integrates cell membranes with conducting polymer electrodes and transistors. To generate the on-chip membranes, the team first optimised a process to produce membranes from live cells and then, coaxed them onto polymeric electrodes in a way that preserved all of their functionality. The hydrated conducting polymers provide a more ”natural” environment for cell membranes and allows robust monitoring of membrane function. The 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. “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 Susan Daniel, associate professor 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 Roisín Owens from Cambridge, 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,” said Owens. The device can be as small as the size of a human cell and easily fabricated in arrays, which allows scientists to perform multiple measurements at the same time, said Anna-Maria Pappa, also from Cambridge and joint first author on both papers. Given the significant risks involved to researchers working on SARS-CoV-2, the virus which causes COVID-19, the scientists said they will focus on making virus membranes and fusing those with the chips. The virus membranes are identical to the SARS-CoV-2 membrane but don’t contain the viral nucleic acid, they said. This way new drugs or antibodies to neutralise the virus spikes that are used to gain entry into the host cell can be identified, according to the researchers.
