In just three weeks, the Innovative Genomics Institute  (IGI) at UC Berkeley built a robotic COVID-19 laboratory.

The "pop-up" system, which has the capacity to handle over 1,000 patient samples a day, will provide desperately needed testing in the Bay Area for those with COVID-19 symptoms and also help public health officials assess the epidemic's spread.

The team behind the development of the technology will begin sampling within the UC Berkeley and City of Berkeley communities this week.

Automating the Test for Coronavirus

The basic way to test for a virus is to isolate RNA from a sample, and then amplify it. A polymerase chain reaction (PCR) makes millions of RNA copies so that the molecules can be more easily studied.

Fyodor Urnov, the IGI's scientific director for technology and translation, wanted to find a way to automate the PCR process for clinical use.

After a March 13 meeting of 59 people within the institute, Urnov began to mobilize the equipment, people, and money needed for the scaling effort.

UC Berkeley labs possessing high-throughput PCR machines donated their equipment to the cause, while IGI established robotic sample handling.

“We threw our R&D mindset into understanding how we can scale [the PCR processing] up and accelerate it, because we understood this fundamental need of the medical community,” said Urnov, a professor of molecular and cell biology who spent 15 years in the biotech industry before coming to UC Berkeley . “Who we are as scientists really connected to an unmet need.”

The lab will run testing based on a process approved by the Food and Drug Administration, but with more efficiency than the many commercial labs that must still run samples manually, one at a time. The high-throughput machines can test more than 300 samples at once and provide the diagnostic result in less than four hours after receiving patient swabs.

Berkeley's Dirk Hockemeyer analyzes patient samples using the robotic COVID-19 testing lab
Dirk Hockemeyer, an associate professor of molecular and cell biology, testing steps in the pipeline that will be used to analyze patient samples. When testing actual patient swabs, Hockemeyer will don full PPE. (Photo courtesy of Max & Jules Photography)

After the emergency modification of state and federal regulations and California’s declared state of emergency, the IGI partnered with clinicians at University Health Services, UC Berkeley’s student health center, and both local and national companies to bring in the necessary robotic and analytical equipment, establish a safe process for sample intake and analysis, obtain the required regulatory biosafety approvals, and train scientists accustomed to conducting fundamental research to analyze patient swabs quickly — with a 24-hour turnaround goal.

In addition to testing, other researchers at UC Berkeley have broken into about a dozen “rapid research response teams” to focus on other COVID-related research projects, including possible improved diagnostics, and new drugs to treat the infection.

"We mobilized a team of talented academic scientists, partnered with experts from companies and pulled together, in a matter of a few days, a group that is operating like a biotech company," said Jennifer Doudna, professor of molecular and cell biology and of chemistry and IGI executive director.

One of the team's talented academic scientists is Abby Stahl, a Postdoctoral Scholar in Doudna's Laboratory.

In a short interview with Tech Briefs below, Stahl explains how the pop-up robotics laboratory works and what other research projects are on the horizon.

Tech Briefs: Can you help me visualize how the pop-up lab works, if I approach the on-campus pop-up lab? What is the sequence of events from arrival to diagnosis?

Abby Stahl: Clinical specimens are collected at off-site medical centers. Samples are taken by a swab, stored in a tube containing liquid, and given a unique barcode for tracking. When they arrive at our lab, we store them in 4 ˚C refrigerator until they're ready to be processed. Once ready, we move the samples to a biosafety cabinet. We unpack the tubes, check the barcodes, and disinfect. Then, we uncap and load them into a liquid-handling robot called a Hamilton Starlet . The Starlet scans the barcode and then moves a fraction of the patient sample into new barcoded plate. At this point, we can seal the plates and store them in the fridge again, or keep processing.

Jenny Hamilton and Shiao use their robotics lab to test samples for COVID-19
Hamilton and Shiao, both postdocs in the lab of Jennifer Doudna, working in a biosafety cabinet to test the diagnostic pipeline for analyzing patient samples. (Photo courtesy of Max & Jules Photography)

Tech Briefs: Is the process automated from here?

Abby Stahl: We currently use a manual pipeline after this, but are gearing up to switch to an automated version. The automated pipeline will use another liquid handling robot called the Hamilton Vantage  to extract RNA from the patient samples and transfer them into another type of plate for a process called qRT-PCR. This is done by another device, the Applied Biosystems 7500  Fast machine. We look for the presence of three different coronavirus genes. The data are uploaded into a laboratory information management system (LIMS), which interprets the results (and checks positive and negative controls to make sure the process worked properly), and determines whether a patient sample is positive or negative. The output is reviewed by the technical team and then confirmed by a clinical consultant, who forwards the results for reporting back to the physician’s office.

Tech Briefs: Why is robotics especially valuable in responding to a pandemic?

Abby Stahl: The Hamilton Starlet is especially valuable because it increases the efficiency of transferring patient samples into the RNA extraction plates and limits contact time that laboratory technicians have with the sample tubes.

The Hamilton Vantage will increase our testing efficiency from hundreds of samples a day to thousands, because we can run 384 samples per plate instead of 96. While this could be done manually in 384-well plates, it would be very prone to human error when handling such small liquid volumes.

Essentially, robotics let us process samples more reliably and more efficiently.

Tech Briefs: Where has this pop-up lab been used so far? And where do you plan to use this in the near future?

Abby Stahl: This pop-up laboratory was built in the Innovative Genomics Institute at UC Berkeley in approximately three weeks, including achieving CLIA certification and passing FDA validation guidelines that have been extended for emergency use during the COVID-19 pandemic. Volunteers were trained in biosafety and HIPAA and fitted for PPE. Equipment and reagents were rapidly sourced, sometimes purchased by IGI and sometimes generously donated by companies and labs in the area. The laboratory will test patient samples for COVID-19 within the UC Berkeley and City of Berkeley communities starting this week and will continue into the future as needed!

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