NEW YORK – LGC Biosearch Technologies has developed an ultra-high-throughput endpoint PCR workflow to enable processing of up to 150,000 samples per day. Called Nexar, the workflow is currently being used for COVID-19 testing at a "megalab" in the UK.
In Nexar, LGC appears to have achieved the highest number of PCR tests per day on a single system. Nevertheless, the firm plans to keep its primary focus on supplying reagents to its customers rather than on developing clinical diagnostics.
The Nexar system is installed at the Rosalind Franklin megalab located in Royal Leamington Spa, in central England. The lab — which is under the auspices of a new agency at Public Health England called the United Kingdom Health Security Agency, or UKHSA — was built to process hundreds of thousands of COVID-19 samples per day with a staff of 1,500 people.
Besides COVID-19 diagnostic testing, the Rosalind Franklin megalab is also carrying out SARS-CoV-2 genotype variant testing using the Nexar system, as well as genome sequencing to confirm variants and identify new mutations. Variant detection PCR testing was incorporated into Public Health England's SARS-CoV-2 surveillance strategies in March of this year to augment sequencing efforts.
Derek Craston, chief scientific officer of Teddington, UK-based LGC, said that the firm started developing the Nexar workflow last spring after learning that a number of the organizations it works with were struggling to meet capacity demands.
"The Nexar has been used in similar workflows in the agriculture biotechnology space for many years now," Craston said in an email, but "the innovation was to pivot to enable trace RNA detection in clinically derived samples."
The Nexar has the potential to enable screening of "very high population numbers at very attractive economics," he said, adding that this could augment the work of the molecular diagnostics industry in delivering improved patient outcomes.
While labs could use banks of instruments to achieve similar capacities as Nexar, "reagent usage and costs will be much higher, as will the required laboratory footprint and complexity," Craston also said.
Mark Dearden is the managing director of LGC Biosearch Technologies, which is LGC's genomics division. In a recent interview Dearden said that forging the ultra-high-throughput Nexar system into "the world's highest throughput PCR system" was enabled by the firm's Array Tape PCR and other proprietary technologies.
The Array Tape technology essentially packages 2-microliter PCR reactions into tiny bubbles on long, flexible polymer strips.
This technology is "incredibly critical" to the firm's high-throughput workflows, Dearden said, because it supports the "scale and capacity, with a rapid turnaround."
It is also fundamental from an economic perspective since the assays are miniaturized.
On its website, LGC notes that Array Tape uses seven times less plastic than a 384-well plate, and the small volumes of the reactions reduce reagent storage, handling, and disposal by 80 percent. Because the tape can be spooled through water bath-based thermal cycling, it also uses 35 times less energy, according to LGC.
Overall, the system can allow users to provide gold-standard PCR with clinical-grade results, Dearden said, at a cost and speed that could enable high-volume testing to be a more critical part of the pandemic toolkit.
Short for Laboratory of the Government Chemist, LGC's roots go back to the late 1860s, when it was founded as a lab to test commercial products for adulteration. It was privatized in the 1990s. The genomics division was subsequently founded in 2008, and rebranded as LGC Biosearch Technologies in 2018. LGC itself was acquired by a consortium led by private equity firms Cinven and Astorg in 2019.
The firm, and the genomics division specifically, have grown dramatically of late, Dearden said, tripling in size in the past six years. This came about in part through the acquisition of firms like Biosearch Technologies, Douglas Scientific, SeraCare, and Lucigen.
In the broader LGC Group, the firm's standards division has made a number of acquisitions in the past few years, as well, Dearden said. Many of these acquisitions, such as Maine Standards or Technopath Clinical Diagnostics, were in the clinical diagnostics area, "where we are seeking to build out our capabilities in reference materials, quality assurance, and proficiency testing around the clinical diagnostics market," he added.
That said, "We've been quite specific in how we've built a portfolio of capabilities that can work together," Dearden also noted.
And, the firm's primary molecular diagnostics strategy still remains in supplying the components that go into diagnostic kits. For example, LGC was among the first firms to offer reagent kits validated for emergency-use SARS-CoV-2 testing by the US Centers for Disease Control.
"Our first focus has been around making sure our oligonucleotides, enzymes, controls, extraction capabilities, and BHQ dyes are readily available to diagnostic developers," Dearden emphasized.
High- and ultra-high-throughput
Nexar is the name the firm uses for the ultra-high-throughput workflow, but it is also technically the instrumentation that performs the liquid handling and manages the Array Tape to process 150,000 samples in a day, Dearden said.
LGC has also developed another high-throughput workflow that processes 4,500 qPCR tests or 35,000 endpoint PCR tests per day.
Both workflows are CE-IVD marked. The high-throughput workflow and SARS-CoV-2 test obtained Emergency Use Authorization from the US Food and Drug Administration earlier this year, while the ultra-high-throughput is going through final stages of clinical validation for EUA, Dearden said.
In the two workflows, LGC has mixed and matched many of the novel technologies it has acquired and developed over the past decade or so — like the Douglas Array Tape, the Biosearch Black Hole Quencher dye, and the Oktopure high-throughput sample prep system.
For example, the EUA high-throughput SARS-CoV-2 testing workflow is built around its IntelliQube technology, which was acquired with Douglas Scientific and also uses the Array Tape.
According to the instructions for use, the EUA high-throughput workflow utilizes the firm's Oktopure high-throughput sample prep, its Hydrocycler2 thermal cycler, as well as its sbeadex viral RNA purification kits, RapiDxFire qPCR Master Mix, EpiScript RNase H- Reverse Transcriptase, SuperROX dye, and BHQ probes and primers.
The Nexar ultra-high-throughput workflow also incorporates the Oktopure and sbeadex viral RNA purification kits for sample prep, and the Hydrocycler2 instrument for thermal cycling, according to the firm's website.
The specific SARS-CoV-2 testing workflow in the Nexar uses the firm's RapiDxFire 1-Step RT-qPCR System, 2019-nCoV CDC-qualified Probe and Primer Kits for SARS-CoV-2, and Seracare AccuPlex SARS-CoV-2 Verification Panel.
Both workflows also use UgenTec software for workflow automation, PCR analysis, and reporting. The UgenTec FastFinder software also enables users to maintain an operational overview of the system using layers of dashboards and reports.
Going forward, LGC hopes Nexar can continue to support the global SARS-CoV-2 pandemic response. The firm hasn't yet added other menu items to the system, but Dearden said the workflow is "reasonably open," and other PCR-based diagnostics that might benefit from ultra-high-throughput could be added. These could include tests for other infectious diseases that can cause outbreaks, like influenza or Ebola, or screening tests for things like sexually transmitted infections.
And although there are not many centralized labs globally that have the test volumes to justify Nexar's throughput, Dearden said LGC is also watching to see if increased awareness of diagnostics encourages more public health screening in the future, particularly using broader respiratory panels.
The Nexar could be adapted to run multiplex PCR panels, but "there is enough real estate [in Nexar] to split out a panel in singleplex," Dearden said, adding that the small reaction volumes also support dividing patient samples into separate compartments.
"As we continue to fight against this disease, and as it continues to mutate ... we feel that testing is still an important tool in our arsenal," he said.