NEW YORK (GenomeWeb) – Having inked a distribution partnership with Oxford Nanopore Technologies (ONT), food testing and analytics startup Clear Labs plans to offer a next-generation sequencing-based platform to rapidly and accurately screen for common pathogenic species in a variety of food-based products.
The Menlo Park, California-based company claims that its updated Clear Safety platform, which will integrate Oxford Nanopore's GridIon with Clear Labs' bioinformatics and laboratory automation, will help food safety professionals prevent and monitor food pathogen outbreaks across the US.
Food safety professionals often use qPCR or enzyme-linked immunosorbent assays (ELISA) to detect antibodies or infectious agents in food samples. However, the techniques cannot immediately distinguish between live and dead pathogenic cells, requiring follow-up tests such as cell cultures to determine if the sample contains a live pathogen.
Clear Labs Chief Commercial Officer Manhi Ghorashi argued that NGS can better help users distinguish between different organisms, as some species can act similar but have varying degrees of pathogenic risk. He explained that sample serotyping is critical to the food industry because knowing the difference in organisms also indicates the appropriate action that food safety experts can take.
However, standard serotyping methods typically require at least three to five days, which Ghorashi said can force users to hold onto millions of dollars worth of food-based inventory until cleared by serology testing.
Ghorashi explained that the Clear Safety platform consists of a box with several different robotic, automated components. While the initial enrichment process can vary on the sample (depending on if it's a food or environmental sample type), a lab technician then transfers the enriched liquid into tubes that sit in a 96-well plate. After registering the tubes with barcodes to track the samples, a technician loads the well plate onto the robotic system.
The robot then performs the chemistry and library preparation steps required on the sample for NGS. After sequencing the sample for about six hours on the GridION system, Clear Safety then applies a cloud-based bioinformatics platform to run sequencing data through custom algorithms, presenting the results to the end user in a generated report.
"Ironically, it’s much more complicated [to identify pathogens] in food versus human DNA," Ghorashi said. "You have that degree of diversity and background noise, depending on the food's source and the condition it was grown in."
According to Ghorashi, Clear Safety can be used in almost all types of vertical food markets, including poultry, meat, diary, pet food, and consumer packaged goods. The firm typically deploys the system within a food safety zone, a microbiology lab, or a third-party manufacturer lab or contractor.
In addition to a recent software update that includes Salmonella serotyping testing in an enriched sample, Clear Safety allows food manufactures and service labs to test for the presence or absence of multiple pathogens and serotypes at the same time. In addition, end users can select if they want to identify the pathogen at the genus, species, or serotype levels.
Ghorashi also noted that the firm plans to release software for Listeria by this summer, and that it will later focus on developing Escherichia coli and Campylobacter assays in the future. He explained that the NGS platform can detect any microorganism since it is not limited to pathogens that the food industry tests for or mandates.
According to Ghorashi, the platform can produce diagnostic results for "north of 400 samples per run" in less than 24 hours.
Ghorashi explained that while Clear Labs' partnership with ONT is officially a distribution agreement, the firm will use the GridIon sequencer and consumables, including flow cells, reagents, and more as part of its platform.
While Ghorashi noted that Clear Safety is generally platform-agnostic, he explained that Clear Labs selected ONT over other NGS firms like Illumina because of the GridIon's rapid turnaround time and inexpensive sample costs, and because it is automated enough to allow the startup to compete in the food safety industry.
Ghorashi said that Clear Labs has been partnering with ONT since early 2017, and that he believes its technology is tailor-made for applied markets including food safety.
"If you want to go into deeper sequencing, such as food authenticity testing, Illumina's sequencing machines become great tools," Ghorashi acknowledged. "For certain applications, like examining microbiomes and testing GMOs, users may want to leverage Illumina's platform."
According to Ghorashi, Clear Labs has raised a total of $45 million in financing since it began in 2013, most recently completing a $21 million series B2 round in October 2018.
Ghorashi declined to disclose the names of any of the 40 food production companies that have run high-volume testing using the updated ONT platform Clear Safety platform. However, he noted Clear Labs is working with groups that make up more than 90 percent of the US poultry market share and more than 80 percent of the pet food market share.
As it navigates through the food safety space, Clear Labs and its NGS platform will compete with a myriad of groups vying for a spot in the food safety business with their own PCR or ELISA-based technologies. Bio-Rad and 3M have both received food-safety testing grants from the US Food and Drug Administration for their PCR and ELISA-based platforms in 2018. Roka Biosciences offers its ribosomal RNA targeting technology to identify food-based pathogens
Qiagen offers its own line of Mericon food-borne pathogen detection real-time PCR assays, which can test for a variety of pathogens including Campylobacter, Cronobacter, and Listeria. Life Technologies — acquired by Thermo Fisher Scientific in 2013 — provides real-time PCR-based tools for foodborne pathogen and quality indicator detection, as well as standard media and biochemical or immunological tests for customers.
In addition, startup LexaGene is also developing a microfluidics-based qPCR platform that produces results within an hour and has been busy signing academic partnerships in the last year.
While acknowledging that PCR platforms have improved accuracy rates — between 98 to 99 percent — for detecting food pathogens, Ghorashi argued that the tests potentially find hundreds of false negatives that move through the supply chain with the hundreds of thousands examined per year, which could lead to massive recall events.
In contrast, Ghorashi said that if Clear Safety misidentifies the pathogen, the platform can eventually detect the disease using other markers. He claims that the platform analyzes the collected DNA sequences by matching them across a database of pathogenic DNA, and that the combination of biomarkers minimizes the possibility of false positives in the sample.
Ghorashi believes that Clear Safety — and NGS in general — will eventually replace PCR-based technology in the food safety sector. It appears that the US Food and Drug Administration agrees, as the agency has launched initiatives over the last few years aimed at better integrating molecular methods such as NGS into the food safety industry.
Last week, the agency proposed new funding across multiple aspects of the food safety system, as it aims to improve its ability to secure the food supply chain and tracking food from source to market.
The FDA highlighted specific technologies — including whole genome sequencing and block chain — to monitor contamination in food, which it noted has simplified detecting the source of food linked to human illness and previous foodborne outbreaks that would have gone undetected. The agency believes that an enhanced ability to trace foods to source during an outbreak will also allow it to "conduct better and more real-time root cause analysis to prevent similar reoccurrences."
"Efficiently tracking and tracing regulated products will enable the FDA to work with stakeholders, including industry producers, to more quickly remove harmful products or ingredients from the supply chain," FDA Commissioner Scott Gottlieb said in a statement. "Such technologies can reduce the time it takes to find a food source from days or weeks to minutes or even seconds, in certain cases."
However, Ghorashi acknowledged that the shift from PCR to NGS has not fully occurred because of issues regarding turnaround time, higher costs, ease of use, and robustness to a level where NGS tools can play in markets like food-based testing.
Clear Labs has not disclosed pricing, but Ghorashi said that the firm has been trying to match the price of PCR testing. While he noted that a premium on NGS testing exists and that food safety budgets are often tight, Ghorashi believes that Clear Labs has done "a good job of bringing the price down to comparable levels to PCR costs."
According to Ghorashi, Clear Labs plans to soon add more biomarkers to the platform, in addition to potential pathogenic risk factors and food quality indicators, such as shelf-life and perishability.
The firm will also focus on investing more in its software, since using NGS generates "hundreds of millions of data points, Ghorashi said. "It turns out that bacterial communities and flora actually function in very similar ways when you look across these massive datasets, and you can start to see patterns emerging among all that microbiome data."
Clear Labs plans to combine several different capabilities into the Listeria testing product scheduled for release later this year. Besides screening for Listeria, the firm aims to integrate resident/transient callings —providing enough information to determine if there's a match between Listeria strains — and to map the bacteria to a facility to show where the strains exist and how they migrate across the facility over time.