(Above:Sarah Harcum making proteins with bioreactors in her lab)

By Paul Alongi

Clemson University researchers arevolunteering their time and resources as part of a statewide effort to developserologic tests that could play a key role in reigniting South Carolinaseconomy and protecting healthcare professionals on the frontlines of theCOVID-19 pandemic.

A test on track to be ready this week would beaimed at detecting antibodies that form in the bloodstream when someone hasbeen exposed to the novel coronavirus and is therefore thought to have alowered chance of re-infection.

Commercial labs are also developing the tests,but some South Carolinians are concerned that the tests will be in short supplyand that the lions share will go to larger states with more purchasing powerand more cases of COVID-19.

Clemson researchers are developing the SouthCarolina tests with colleagues from the University of South Carolina, PrismaHealth and the Medical University of South Carolina.

Delphine Dean is overseeing the Clemsonportion of the work as the Clemson lead for the states Serological Testing andDiagnostic Working Group.

Were all working on it together, said Dean,who is the Ron and Jane Lindsay Family Innovation Professor of bioengineering.Many of the barriers between institutions that sometimes slow downcollaboration have been removed. Everyone has been working around the clock tomake these things go much faster than typically happens.

Before any test is deployed, it would need tobe validated for effectiveness to meet Food and Drug Administrationregulations.

The test that will be available this week isaimed at checking healthcare professionals for antibodies. The idea is thatthose who test positive for the antibodies could be cleared to re-enter publiclife, allowing them to work with minimal concern they could come down withCOVID-19 or infect others.

About 500 to 1,000 tests could be ready as earlyas this week, less than a month since the project started, researchers said.

The two Clemson researchers working on thetest are Mark Blenner, the McQueen Quattlebaum Associate Professor of chemicaland biomolecular engineering, and Sarah Harcum, professor of bioengineering.

Blood samples would need to be tested in alab, which limits how many can be done. In a parallel effort, Clemsonresearchers are working to create tests that could take saliva, urine or bloodand show results with a color change in as little as 15 minutes, similar to ahome pregnancy test.

Researchers involved in developing those testsare: Blenner, Terri Bruce, research assistant professor of bioengineering anddirector of the Clemson Light Imaging Facility; Dean; Harcum; and R. KennethMarcus, University Professor of chemistry.

The tests would be an improvement on currentmethods. Antibody tests that check for immunity require a blood draw and areinaccurate and scarce, Blenner said. Testing directly for the virus itselfrequires an uncomfortable nasal swab and puts healthcare workers at aheightened risk of catching the virus, he said.

Martine LaBerge, the chair of Clemsonsbioengineering department, said all the researchers are volunteering theirtime, efforts and resources to help the state, as it faces the unprecedentedchallenges posed by the COVID-19 pandemic.

They are working tirelessly to protect thehealth and safety of South Carolinas healthcare professionals and the generalpublic, said LaBerge, who is playing a central role in coordinating Clemsonsresearch response to the pandemic. Institutional barriers are coming down sothat we can work together as one South Carolina. I offer all those sacrificingsleep and time with family my deepest gratitude.

The process to develop the tests starts withBlenner, who is making spike proteins, which give the novel coronavirus itsdistinguishing feature and is believed to be how the viral infection ismediated.

In his lab, Blenner puts the DNA for the spikeproteins inside of human or hamster cells. When the cells grow, they producethe spike proteins, which will ultimately serve as the key reagent in theantibody tests.

Our group is going to make a stable cell linethat we can scale up, Blenner said. Right now the procedure is not meant tomake a lot of protein. Its meant for quick protein production. Im going tomake a productive cell line and work with Sarah Harcum to get that in largerbioreactors.

Harcum said she will put the cells incomputer-controlled bioreactors that can sense oxygen and pH levels. Pumpscarefully control the nutrients that feed the cells.

I grow cells to make them happier so theymake more protein, Harcum said. Normally, I look at how to makepharmaceuticals, but the pharmaceuticals I make are proteins, which makes thisCOVID-19 work a good fit for what I do.

Once she has the protein grown, Harcum willthen purify it so that it can be used in the diagnostic tests.

Meanwhile, Bruce, Marcus and Dean are startingto lay the groundwork for simple tests that could reach large numbers ofpeople.

What we really need is something simplethats a colorimetric test that can be done in under 15 minutes at the point ofcare, Bruce said.

The team is working to improve upon acommercially-developed enzyme-linked immunoabsorbent assay, or ELISA, thatchecks blood samples for antibodies.

Antibodies are plentiful in blood but less soin saliva. One of the challenges in developing a saliva-based test is isolatingthe antibodies.

To do so, Marcus and Bruce are turning tocapillary-channeled polymer fiber-based films, a technology they have been researchingfor years.

Antibodies exist in this tremendously complexsoup, and what you would like to be able to do is pull them out of the soupselectively in a fairly high-throughput fashion, Marcus said. We can modify our fibers so that the only thingsthat stick are the antibodies.

Clemson researchers are working to make aprototype, but a manufacturer would be needed to produce large quantities ofthe test, Bruce said.

Dean, who is helping develop the opticalportion of the test, said it could also be possible to use the fibers tocapture the virus itself from urine. There is evidence that the virus comes outin urine after it is no longer detectable in blood, she said.

Patients could maybe test themselves athome, Dean said. The same principle could be used to test waste streams. Ifyou wanted to do population monitoring, you might be able to get a sense forwhat percent of the population has the virus.

Researchers said they are finding ways to payfor the development of the tests with existing funds but that eventually theywill need financial support, particularly when the semester ends next month.

We are going to need lab supplies andgraduate student salaries, and we could accelerate development by outsourcingsome of the work, Dean said. Typically, when we launch big projects, we applyfor federal funding, a process that normally takes months, if not a year ormore. But time is of the essence, and we are finding ways to quickly ramp upwork. What we need most now is the funds to help keep the work going.

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Researchers respond to urgent call for COVID-19 testing - Greenville