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How one research lab morphed into a COVID-19 testing lab

July—In the early days of the COVID-19 pandemic, when the University of California, Berkeley’s Innovative Genomics Institute decided to rapidly shift gears from conducting research to testing the community for SARS-CoV-2, some insiders may have thought the university was biting off more than it could chew under a tight timeframe. Yet a look at the lab 23 days later surely had any doubters eating their words.

The research lab, led by executive director Jennifer Doudna, PhD, renowned for her pioneering CRISPR (clustered regularly interspaced short panlindromic repeats) research, had to not only put in place a new virus test, it had to create a Health Insurance Portability and Accountability Act-compliant laboratory information management system to manage patient testing records and conform to Clinical Laboratory Improvement Amendments regulations, requirements it did not have to adhere to when it operated in a research capacity. And all of this, and more, had to be done at breakneck speed on a campus that did not have a medical school or hospital.

Dr. Urnov

When the project began, on March 14, recalls Fyodor Urnov, PhD, the institute’s scientific director for technology and translation, UC Berkeley’s student health center had at least a week-long turnaround for student SARS-Cov-2 test results, and there was a dearth of rapid testing in Berkeley and surrounding communities, even for first responders.

“We could not have a month-long research and development effort and then a month-long period to set things up,” says Dr. Urnov. “It was just not an option.” Therefore, the institute purchased Third Wave Analytics’ cloud-based Lockbox LIMS and, working with the vendor, customized it to accommodate the needs of its SARS-CoV-2 test. Within approximately three weeks, the system was up and running.

The LIMS “harvests the data automatically — what specimen was requisitioned, by whom, when it arrived, who processed it, on what robot, using what procedure, when, what happened, and what was the result,” explains Dr. Urnov. “It does that in a seamless fashion.” More specifically, the LIMS provides such functionality as the ability to create records of samples when sample barcodes are uploaded, as well as automated record updating during sample testing, according to correspondence in Nature Biotechnology detailing the process of setting up the new lab (Amen AM, et al., published online June 18, 2020). Among the LIMS’ many other capabilities are customized dashboards for tracking samples throughout the testing process and automated analysis of control and sample data to generate a final patient result immediately after raw data are uploaded.

To meet specific user needs, the institute created two LIMS interfaces — one for the university and one for the community. To test UC Berkeley students, the team built a direct interface to the student health center’s EHR system. When a physician affiliated with the health center orders a lab test through the EHR, a de-identified barcode is linked to the order and automatically routed to the LIMS. Once the test is completed, the LIMS returns the barcoded data to the EHR for placement in the patient’s medical record.

This process is not suitable, however, for orders coming from outside the university’s health care system, Dr. Urnov says. “Everybody else has their own EHR. Somebody has Epic, somebody has something else. So, we solved that once and for all by building our own physician portal.” The secure HIPAA-compliant portal resides on the Salesforce.com platform. Physicians with login credentials can use the portal to enter the required testing information, initiating a test order that will be managed by the LIMS from start to finish.

The necessity to move quickly also prompted the lab to adopt Thermo Fisher Scientific’s TaqPath COVID-19 Multiplex RT-PCR diagnostic kit, Dr. Urnov says. While the institute’s research scientists have extensive experience developing polymerase chain reaction-based tests, Dr. Urnov decided it would be faster to take a commercial test kit and adapt its workflow to suit the lab’s needs.

To this end, the lab added automation to boost throughput, Dr. Urnov says. “Regular laboratory equipment is not set up to process 1,000 of anything. It’s set up to process 10 of something. So we took the kit apart and we looked around for the best automation hardware — robots that could do hundreds and hundreds of samples without the ‘error proneness’ that humans are known for.”

The new workflow involves using Hamilton’s Microlab Vantage liquid-handling system in the RNA extraction phase, followed by Applied Biosystems’ QuantStudio 6 Flex Real-Time PCR system to run the test, after which the LIMS software analyzes the test data, Dr. Urnov says. The combination of equipment greatly increased processing capacity, he adds. “The bottom line is, in a setting where 100 specimens take three hours, we now have a setup that will do 1,000 specimens in 12 hours.”

The institute also made a workflow change to the test by using the virus inactivation solution DNA/RNA Shield, from Zymo Research, to protect staff handling patient specimens. When a health care provider obtains a specimen and puts the swab in a tube, DNA/RNA Shield inactivates the virus in a way that still allows the lab to measure nucleic acid levels, Dr. Urnov explains.

Because Thermo’s equipment is being used in a manner that does not fall within its prescribed workflow and because of other workflow changes introduced by the lab, the test is classified as laboratory developed by the FDA and Centers for Medicare and Medicaid Services.

Dr. Green

With the adaptations came hiccups, says Ralph Green, MD, PhD, who is laboratory director for UC Berkeley University Health Services, as well as professor of pathology and laboratory medicine at UC Davis, outreach director for UC Davis Outreach, and lab director for UC Davis’ student health laboratory. In one instance, says Dr. Green, difficulty finding the right tubes due to supply bottlenecks led the lab to purchase tubes that were shorter than the recommended size. The shorter size prevented the automated probes from reaching the optimal tube depth. As a workaround, says Dr. Green, someone in the laboratory turned to a 3D printer. “They used a 3D printer to produce a kind of mini-platform to put in the bottom of each of the 96 positions and then put the shorter tubes on top of those platforms. It worked.”

In tandem with such efforts to transform the institute into a clinical lab that could serve the community, Dr. Green guided the team through the process of meeting FDA standards, state regulations, and CLIA requirements. This included filing paperwork with state regulators and CMS to extend the UC Berkeley student health center’s CLIA certificate to the new clinical laboratory. It also involved obtaining necessary approvals to allow members of the institute’s team to work in a CLIA lab.

As CLIA lab director, Dr. Green remotely oversees regulatory compliance issues for the lab and proficiency testing. He also reviews and validates test results, which may involve making decisions about the need to retest patients based on inconclusive results. The laboratory oversight is conducted through regular phone calls and Zoom conferences, he says.

After the COVID-19 lab went live, UC Santa Cruz Molecular Diagnostic Lab approached Dr. Green, who also serves as lab director for the UC Santa Cruz Student Health Center, about playing a similar role in that lab’s effort to establish a temporary SARS-Cov-2 testing site. Consequently, Dr. Green helped shepherd that lab through the necessary regulatory requirements.

Back at Berkeley, the Innovative Genomics Institute has partnered with multiple organizations in the vicinity, including community health centers, to offer free testing. It will stay the course, says Dr. Urnov, until COVID-19 testing is no longer needed in that area. — Renee Caruthers

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