Researchers at UC Santa Cruz are testing a novel nanosensor technology that could provide rapid, low-cost serology tests with high sensitivity for detecting and quantifying antibodies to the coronavirus that causes COVID-19.
The detection of antibodies to the virus in a blood sample indicates that a person has been infected and developed an immune response. Whereas diagnostic tests for the virus itself identify active infections, serology tests can identify people who have already been infected and have presumably developed some level of immunity (although many uncertainties remain about immunity to the novel coronavirus). Serology tests are important for quantifying the actual number of cases of COVID-19 that have occurred, including asymptomatic cases and those who have recovered.
Nader Pourmand, professor of biomolecular engineering in the Baskin School of Engineering at UC Santa Cruz, is evaluating a serology testing platform derived from nanopipette technology developed in his lab. He has received a $75,000 grant from the COVID Catalyst fund established at UC Berkeley to provide rapid funding for COVID-19 research at the institutions within the Bay Area Virus Network.
“An important part of this is not only the funding, but also having access to serology samples from UCSF for evaluating our technology,” Pourmand said.
Two main types of COVID-19 serology tests are currently available—laboratory tests that can quantify the level of antibodies in the blood (using a technique called ELISA), and rapid tests that indicate the presence or absence of antibodies and use a small, portable platform (called lateral flow assays). Reports of inaccurate results from some of the rapid tests on the market have raised questions about how useful they are. In addition, the rapid tests do not measure the level of antibodies, which is valuable information for evaluating immune responses, identifying potential plasma donors, and tracking disease progression, Pourmand said.
The new nanosensor technology offers the potential to rapidly detect and quantify antibodies to the coronavirus in a finger-prick blood sample in less than a minute, using disposable cartridges and a relatively inexpensive ($100) reader that could be available at pharmacies, clinics, and other points of care.
The cartridges use nanosensor chips designed by Pinpoint Science, which has licensed from UCSC several patents for Pourmand’s nanopipette technology. (Pourmand is chief scientist of Pinpoint Science.) Pourmand’s lab originally developed the nanopipette technology for nondestructive, single-cell analysis of living cells, but the glass nanopipettes are impractical for large-scale manufacturing. Pinpoint Science developed a four-channel nanosensor chip which is fabricated by the semiconductor company Analog Devices.
At the tip of each channel is a tiny pore, and the device measures the electric current through the pore. Viral antigens are immobilized on the nanosensor tip, and when the targeted antibodies bind to the antigen probes, a change in the current indicates the concentration of the target. This provides a very precise measure of the level of Covid-19 antibodies in a specimen. Pinpoint's initial testing of the nanosensor chips has shown target detection at levels as low as 1 femtogram per milliliter, or roughly 100,000 times more sensitive than conventional immunoassays, Pourmand said.
“Hundreds of molecules can bind to the opening of the pore, and the change in current gives an indication of how many molecules there are,” he said. “Our sensors are very sensitive, more sensitive than other technologies, and it’s a small system that’s easy to use and gives results in seconds.”
Pourmand’s lab is currently testing the chips and optimizing the conjugation of the antigen probes to the nanosensor tips. Then they will test the system using real blood samples and compare its performance with current technologies.
While Pourmand’s lab at UCSC focuses on evaluating the nanosensor technology for antibody testing, Pinpoint Science is evaluating its use for detecting viral antigens as a rapid diagnostic test for active infections. For this approach, the target and the probe are flipped, with antibodies immobilized on the nanosensor tip and viral antigens detected and quantified when they bind to the antibody probes.
“One of the goals that we and other groups are working toward is to enable people to do the testing themselves. We want people to be able to stay at home for testing and follow up with their doctor if necessary,” Pourmand said. “The nanosensor technology is inexpensive and easy to use, so it lends itself to that kind of concept.”