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A day in the race against COVID-19

HP microfluidics technology is helping speed up the search for effective treatments to combat the novel coronavirus.

By Sara Harrison — October 27, 2020

Just outside the medieval walled city of Siena, the Tuscan hill town known for its famed Palio horse race, a different kind of race is happening at Toscana Life Sciences Foundation. This one is on a microscopic scale, as senior scientist Claudia Sala and her team research a treatment for COVID-19, which is projected to cause nearly 2.7 million global deaths by year’s end.

Sala studies monoclonal antibodies, or mAbs, tiny proteins the human body produces to fight off infections from bacteria and viruses. By finding and cloning the right mAbs, she and other scientists are hoping to create a powerful therapy that could help treat COVID-19 and even protect frontline workers. With help from HP inkjet printing technology and other partners, researchers could find those antibodies in record time. 

“In normal conditions, the production of monoclonals would take at least one year,” says Sala. She’s hoping to get these out in just six short months and to start clinical trials this December. Here’s a look at Claudia Sala’s typical day inside the lab.

8:00 A.M. / The search kicks off 

Sala lives just outside Siena, once a center of political and cultural power that rivaled Florence in the 13th century. Its population was devastated by the Black Death and the city never recovered its former glory, something the scientist reflects on every time she glimpses the town’s ornate but never-finished Duomo. Her short commute takes her to Siena’s suburbs, where Toscana Life Sciences is home to nine research projects — including the Monoclonal Antibody Discovery (MAD) Lab, led by Sala — all focused on making biomedical advances.

Sala first tackles a mountain of emails each morning. Before COVID-19, she and her team were searching for mAbs that could fight off antibiotic-resistant bacteria. But as the pandemic swept through Northern Italy in late February, Sala and the lab’s principal investigator, Rino Rappuoli, decided to temporarily abandon their bacteria research and devote the lab’s energies and resources to finding a treatment for COVID-19.

Researcher looking into lab samples with optical microscope in HP microfluidics team against COVID-19.

Alberto Bernasconi

Emanuele Andreano, a postdoctoral fellow at Toscana Life Sciences, views lab samples using an optical microscope.

The MAD Lab is among a handful of research institutions benefiting from HP’s donation of D300e BioPrinters, supply cassettes, and training to help accelerate drug and vaccine research to combat COVID-19. The BioPrinter emerged from HP’s expertise with microfluidics, which is a broad research area that’s enabled by precision placement of microscopic amounts of fluid. 

Monoclonal antibodies work because they bind to the surface of a bacterium or virus and keep it from attaching to cells and replicating. While mAbs can be harnessed to treat a range of pathogens, each treatment relies on an antibody that is uniquely suited to bind to each virus or bacterium. “You need a very specific key to open a specific door,” says Sala. Testing endless variations of those “keys” to find the right one that will fit into COVID-19 is a slow process—unless you have a printer to set up and run those tests for you. 

9:00 a.m. / The team checks in 

The group has doubled to 14 members since February as Sala added scientists with specialties in cell and virus biology. Sala huddles with immunologists Anna Kabanova and Emanuele Andreano and the biologists and data scientists to review the previous day’s results and discuss next steps.

Monoclonal antibodies are naturally produced by the human body, so Sala doesn’t have to go through the long approval process necessary for chemically made drugs. She hopes that will help the lab get the mAbs into clinical trials sooner and get the treatment to people faster. Eventually, the dream is to create an oral spray, but for now, she’s focused on delivering the mAbs through an intramuscular or subcutaneous injection that acts as a prophylactic to boost a patient’s immune system. The medication could be given to healthcare workers or essential workers before they head into hot spots.

While mAbs do offer protection, they usually only last two or three months, because unlike a vaccine, monoclonals don’t train the human immune system to respond on its own. Once the monoclonals leave the body, the protection is gone.

11:00 a.m. / Isolating the antibodies 

Sala oversees the lab’s graduate and postgraduate students as they run experiments. Researchers can’t always stay six feet apart in the lab, so in addition to a lab coat and gloves, Sala also dons a face mask when she heads inside.

The first step in finding the right mAb is to analyze the blood of COVID-19 patients. Sala’s lab collected samples from local hospitals and isolated the memory B cells, the part of the immune system that produces antibodies, cultivating them in the lab.

HP D300e BioPrinter used by lab assistant.

Alberto Bernasconi

The HP D300e BioPrinter can pipette the 384 wells on a plate with samples in minutes, as opposed to hours by a lab assistant.

A mAb that disrupts that process will keep the virus from replicating and causing a serious infection, but it isn’t a vaccine. “I would say they’re complementary,” says Sala. “A monoclonal can be used in an emergency situation.” 

Growing these cultures requires an expensive supernatant — a medium that encourages B cells to grow and produce mAbs — and even a good batch of antibodies only yields about 50 microliters of sample. Once the scientists have coaxed antibodies out of the memory B cells, tools like the D300e BioPrinter help researchers dose each sample more precisely, and allow them to run more tests with smaller amounts of each sample, preserving vital resources. 

12:00 p.m. / Time for an insalatona 

Work continued at Toscana Life Sciences even during the height of the pandemic in Italy, but a lot has changed. Now, the cafeteria where Sala eats lunch every day is less collegial, with people sitting apart and eating in spaces divided by plastic shields. And at times during this project, she couldn’t sit and enjoy her meal, stopping only long enough to finish a salad or sandwich before heading back to work. As the team moves into later phases of testing, Sala occasionally has a moment to pause, enjoy a break, and chat with colleagues from other labs. 

2:00 p.m. / Finding the best fit 

The next step is to test each mAb to see how well it binds to the spike protein: The stronger the bond, the better the treatment will be. But out of the 4,000 antibodies Sala’s team collected, only 300 can bind to SARS-CoV-2 and only a few will be good options for a treatment. Running tests on those hundreds of antibodies to find out which are the best takes a long time, and setting up those tests — mixing the antibodies with the right reagents, pipetting each of the antibodies into 384 tiny wells — takes a lot of work.

That’s where HP’s bioprinters come in again. Printing ink on a page isn’t so different from depositing tiny amounts of fluid into well plates: The printer has to be able to steadily control the volume of liquid it releases and deposit it in exactly the right spot. “Think of the amount of directional control of an amount of fluid that we have to have to print a photo on your desktop printer. That’s thousands of droplets per square inch,” says Annette Friskopp, global head and general manager of Specialty Printing Systems at HP. “Already we have a lot of capability handling the directionality of the drop and where it’s going.”

Lab scientists researching COVID-19 treatments pictured together standing on staircase.

Alberto Bernasconi

MAD Lab scientists Emanuele Andreano, Claudia Sala, Marco Troisi, and Anna Kabanova are members of the team researching COVID-19 treatments.

For biological labs like Sala’s, HP also had to figure out how to distribute different kinds of fluids accurately and reliably, even though every mixture has a different surface tension and viscosity. The D300e helps the lab screen for the right mAbs much faster, both in its COVID-19 research and in other projects on antibiotic-resistant bacteria. While it might take a researcher hours to get all 384 wells ready, the HP D300e BioPrinter can do it in just three or four minutes. 

 “It’s extremely fast, it’s extremely precise, and it’s extremely reliable, which are all advantages for the customers,” says Raffaella Fior, a research engineer at HP.

6:00 p.m. / Awaiting clinical trials 

After another round of emails, Sala checks in with the researchers one last time, says good-bye to her colleagues, and gets in her car for the five-minute drive home. When the project first started, she says, they all worked late into the night running tests. “We had quite long days, including weekends,” she recalls. 

Once the team found the most promising monoclonals for COVID-19, they sequenced the mAbs’ DNA and then cloned them, producing an army of identical antibodies that are highly specialized to bind to the SARS-CoV-2 virus and stop an infection, before people develop serious symptoms.

Now, workdays are a little shorter as the researchers wait to start human trials. Sala’s lab has already sent samples to the University of Georgia for testing in animals and is also working with a company in Italy that uses bioreactors to grow large enough quantities of the mAbs to start phase one clinical trials at the much faster pace this pandemic requires.

Sala’s team is one of several around the world testing mAbs as a possible treatment for COVID-19, and she says that other benefits could be that the mAbs her team identifies are more reliable to produce on a large scale, or have a greater affinity for SARS-CoV-2, making a more potent product or one that could be combined with others to create an even more powerful treatment.

Sala says racing to find a cure has been exhausting and intense, but also incredibly rewarding. Everyone in the lab is pulling together, working on something they believe could help millions of people. “I think this was the motivation that helped us push the boundaries,” she says. 

 

RELATED: The promise of microfluidics and rapid testing.
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