Adarza Biosystems Inc.’s Ziva platform can simultaneously detect hundreds of proteins, antibodies, or substrates from a single drop of blood, plasma or serum, providing insight into an individual’s immune response. That could be critical for both surveillance and diagnostic purposes as the nation prepares for a likely second wave of the novel coronavirus in the fall when multiple respiratory pathogens will be circulating.

Ziva uses arrayed imaging reflectometry (AIR), a technology co-developed by Ben Miller, a founder of St. Louis-based Adaraza and professor of dermatology, biochemistry and biophysics as well as biomedical engineering at the University of Rochester in New York.

“A lot of companies have developed clinical tests for COVID antibodies,” Miller told BioWorld. “What’s common to many of those tests is the use of a single antigen, one protein from the SARS-CoV-2 coronavirus on the test. While they can detect antibodies to that protein, they don’t provide a picture of what’s going on in a person’s immune system.”

In addition, sometimes those tests detect infection with the novel coronavirus when a patient has something far more mundane.

“Those that detect the S or spike protein may show positivity for COVID-19 in some cases when they are actually detecting antibodies to one of the coronaviruses that cause the common cold,” Adarza CEO Bryan Witherbee told BioWorld.

Knowing which coronavirus or other pathogen is causing symptoms is critical and sequential testing is both costly and time consuming.

“It’s important to discriminate between responses to SARS-CoV-2 and other responses,” Miller added. “We put all those proteins [to identify various pathogens] on a chip, and get detailed high resolution profile by using a 15-plex array.”

The technology

The label-free platform can simultaneously assess up to 100 biomarkers from a single sample and can run 1,000 samples a day – enabling production of up to 100,000 datapoints in 24 hours.

The system is based on a silicon chip that is “almost perfectly antireflective,” Miller explained. “It’s like when you have a perfectly clean computer screen and someone touches it and you see the fingerprint for the rest of the day. The biosensor uses the reflection off a silicon chip instead.”

Creating a substrate with a coating that reduces reflectance to near zero forms a sensor that can detect picoscale changes on its surface by variance in reflected light. The device uses a laser beam which reflects off the surface of the silicon chip. A digital camera captures the reflected image, which displays as bright and dark spots.

If no target molecules are present, the antireflective coating absorbs all the light from the laser. In contrast, light spots or reflective areas in the image correspond to thicker surfaces, where target molecules have attached to probes. The system quickly evaluates the image and displays the results on an analysis screen within minutes.

By measuring the mass and size of the target, the system can detect any combination of molecules that bind in nature, making the process extremely flexible as well as efficient. The system can measure molecules as small as one kilodalton up to 18,000 kilodalton simultaneously.

The applications

Last fall, Miller published a paper with other participants in the National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Surveillance program that demonstrated the ability of AIR to rapidly screen small amounts of blood for antibodies to all types of viruses common to humans as well as to animals as part of a pandemic surveillance exercise.

Now, the company is applying the technology to advance knowledge about the novel coronavirus and possible pharmacotherapeutic and preventive measures.

“We’re excited about the ability of the system to give more information to researchers around COVID-19,” said Witherbee. “We’re talking with collaborators about applications for development of specific monoclonal antibodies against COVID as well as vaccines.”

Miller has submitted another study for publication on the initial development of a SARS-CoV-2 assay and results from a small set of human samples, which he is continuing to expand.

The technology is also being used in a variety of interventional clinical trials to determine how therapies might change a patient’s response to COVID-19.

“There’s so much fascinating basic research to be done,” Miller said. “How does your exiting immunity to other viruses affect response to COVID-19? If you had a strong response to a particular circulating cold virus, do you respond differently to COVID-19 than someone who didn’t? We don’t know yet.”

Adarza hopes that its antireflective technology will help shed more light on those questions and others that could lead to a critical breakthrough against the novel coronavirus.