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Clinical Trials on a Chip researchers plan to build and test common and rare disease models to help improve the clinical trial process.

Approximately 85% of late-stage clinical trials of candidate drugs fail because of drug safety problems or ineffectiveness, despite promising preclinical test results. To help improve the design and implementation of clinical trials, the National Institutes of Health has awarded 10 grants to support researchers' efforts in using tiny, bioengineered models of human tissues and organ systems to study diseases and test drugs. One major goal of the funded projects is to develop ways to better predict which patients are most likely to benefit from an investigational therapy prior to initiating clinical trials.

The awards total more than $6.9 million in the first year, and approximately $35.5 million over five years, pending available funds. They are administered through a new program, Clinical Trials on a Chip, which is led by NIH's National Center for Advancing Translational Sciences (NCATS) in conjunction with several other NIH Institutes and Centers, including the National Cancer Institute, the National Institute of Child Health and Human Development, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Tissue chips, or organs-on-chips, are 3-D platforms engineered to support living human tissues and cells and mimic complex biological functions of organs and systems. Tissue chips are currently being developed for drug safety and toxicity testing and disease modeling research, including on the International Space Station. Clinical Trials on a Chip is one of several initiatives that are a part of the NCATS-led Tissue Chip for Drug Screening program, which was started in 2012 to address the major gaps in the drug development process.

University scientists are adapting existing research to develop tests to detect and improve our understanding of COVID-19. Examples include projects led by Martin Zand, senior associate dean for clinical research at the Medical Center; Benjamin Miller, a professor of dermatology and biomedical engineering; and James McGrath, a professor of biomedical engineering.

Zand is working on the finger-stick test, which uses patented technology that detects immunity to more than 50 strains of flu. The test comes in an easy-to-mail kit similar to those that test blood sugar for diabetes. "We're hoping this could make COVID-19 vaccine trials faster and more convenient for those who volunteer for them," says Zand.

Miller's lab hopes to find the virus with optics at the nanoscale. The lab is developing tiny sensor chips that use coronavirus proteins to "very quickly" detect the presences of immunoglobulin G and M antibodies that humans develop within two days of exposure to the virus. "The problem right now is actually getting patient samples," says Miller. "Meanwhile we are optimizing our assays with 'normal' serum samples doped with coronavirus antibodies—basically making artificial patient samples."

McGrath is using ultrathin membranes—less than 200 nanometers thick—to determine whether individuals have been infected with COVID-19. He can apply the membranes as a sensor and as a platform for discovering pathogenic mechanisms. McGrath is eyeing an inexpensive device similar to a pregnancy test that could be used in low-resource communities around the world.

"It will likely take more than a year to develop a vaccine, so COVID-19 is going to be with us for some time," says McGrath. "If we move quickly but deliberately, I think the device could be ready in time to help with the current pandemic."

Amid growing alarm over the plastic that pollutes our environment, biomedical and optics researchers at the University of Rochester are working to better understand the prevalence of microplastics in drinking water and their potential impacts on human health.

They are collaborating with SiMPore, a company that uses nanomembrane technology initially developed at the University, to devise ways to quickly filter and identify particles of plastic 5 mm or smaller in drinking water samples. They will then test the ability of these particles to cross a microscale barrier that simulates the lining of a human intestine.

"We want to see to what extent the particulates that you consume in your drinking water can pass through your gut and into your other organs," says Greg Madejski, a postdoctoral fellow in the laboratory of James McGrath, professor of biomedical engineering. Madejski is coordinating the research with the lab of Wayne Knox, professor of optics. Both McGrath and Knox are affiliated with the Materials Science Program.

Microplastics are used as ingredients in cigarette filters, textile fibers, and cleaning or personal care products. Others result when larger plastic items are worn down by sun, wind, and waves. They can be found on mountaintops and at the bottom of the oceans; in the air we breathe and in the water we drink. Exactly how many microplastics are absorbed by humans, and how much harm it is causing them has been hard to assess because the particles— below 100 microns—are so small and difficult to detect.

"These are particles that you couldn't pick up with tweezers; that you can't even see with the naked eye," Madejski says. They elude the "traditional method of skimming the surface of water with a plankton net and collecting everything," he says.

Instead the researchers will filter water through sheets of silicon nitride a hundred times thinner than the diameter of a human hair. These SiMPore nanomembranes, based on prototypes initially created in the McGrath lab, have micron-sized slits in them. "That allows us to catch micron-sized debris," Madejski says. "And because the sheets are so thin, you can filter a significant amount of water through them without a lot of pressure."