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Talis Biomedical Developing 'SlipChip' Microfluidic POC Platform for Genotypic, Phenotypic Testing


NEW YORK (GenomeWeb) – With $10 million in recent funding, Talis Biomedical is developing a point-of-care, sample-to-answer platform that incorporates a digital microfluidic technology called SlipChip.

The funding will also support development of pathogen identification and antibiotic susceptibility testing (AST) for bloodstream infections and for chlamydia and gonorrhea, the company said.

A startup with offices in Menlo Park, California and Chicago, Talis was founded by Brian Coe and Rustem Ismagilov, a professor of chemistry and chemical engineering at the California Institute of Technology , as well two researchers who did their graduate work with Ismagilov, Liang Li and Feng Shen. Talis, which licensed technology from CalTech and the University of Chicago, was originally called SlipChip Corp but has since changed its name to Talis. Ismagilov serves as a board member.

"The founding vision of the company, which remains our guidepost today, was to develop an affordable, easy-to-use, sample-to-answer platform that will deliver laboratory-quality results at the point-of care within minutes in order to enable doctors to make timely, informed treatment decisions," Coe said in a recent interview.

In the long run, Coe said, the POC platform will deliver women’s health and sexually transmitted infection tests, as well as assays targeted to primary care offices for infections like flu, strep, and respiratory syncytial virus.

Talis intends to target customers in physician offices, urgent care centers, emergency rooms, and outpatient clinics for its menu in women’s health and primary care. Hospitals will be a main target for the bloodstream infection product lines, Coe said.

Broadly speaking, SlipChip is just one component of the sample-to-answer platform Talis is developing.

The firm's suite of technologies also includes proprietary sample prep capabilities, bioinformatics, and low-cost instrumentation, Coe said.

Talis and the Ismaligov Laboratory have also collaborated on a number of projects including a multiyear DARPA program to develop a point-of-care molecular platform for use in limited resource settings, Coe said, and more recently, to develop a new approach to rapid phenotypic antibiotic susceptibility assessment in gonorrhea, which is funded by a CARB-X contract.

As described in a seminal paper in 2010, SlipChip also distinguishes itself as an easy-to-manufacture microfluidic-based consumable chip. Reaction wells in a bottom plate are preloaded with reagents, and sliding the top plate across it partitions a sample into uniform, nanoscale reaction volumes.

The technology was originally developed at the University of Chicago, where Ismagilov occasionally had research discussions with Coe's father, a professor of nephrology there whose work became the seed for a kidney stone analysis lab called LithoLink where Coe, the son, was CEO from 1995 until that company was acquired by LabCorp in 2006 for an undisclosed amount.

Coe then served as a senior vice president at LabCorp for nearly six years. He was introduced to Ismagilov by his father and was "taken by the power of SlipChip to deliver highly quantitative results in a structure that is low cost and very precise," he said, as well as by the technology's flexibility to do things like multistep and multiplexed reactions, and "digital" reactions with stochastic confinement.

Ismagilov and his colleagues previously demonstrated SlipChip-based digital LAMP could be used to detect HIV-1 RNA and have suggested it could be used for other applications, such as protein crystallization, cell culture, and immunoassays.

The new $10 million funding to Talis includes awards from the National Institutes of Health and CARB-X.

The NIH funding is for development of a direct-from-blood pathogen ID assay and the subsequent phenotypic susceptibility of the identified organisms, Coe said. For sepsis, "today it takes literally a couple of days to know whether there is an infection and what it is," Coe said. The firm is looking to achieve pathogen detection in less than 30 minutes, as well as subsequent antibiotic susceptibility testing, or AST.

Last year the Ismagilov lab reported a rapid, culture-free phenotypic test using SlipChip. The technique was designed to work directly from urine samples using digital loop-mediated isothermal amplification, or dLAMP. In that research, identifying E. coli in clinical urine samples took 15 minutes, while subsequently measuring a onefold-difference drop in bacterial replication rate indicating antibiotic susceptibility of E. coli took less than 30 minutes. 

Time-to-result is important in sepsis management because mortality rates increase with delay to diagnosis. However, direct-from-blood testing would also be useful, as would an inexpensive assay, Coe said. "We believe we will have a very economically reasonable approach," he said.

The CARB-X funding, meanwhile, supports the development of a chlamydia and gonorrhea assay, particularly focused on addressing the growing crisis of gonorrhea resistance, Coe said.

The funded work "will advance the sample-to-answer platform that would provide a rapid identification within minutes," he said, noting that this is the first step to antibiotic stewardship. "In parallel, we are collaborating with Caltech to further the development of a phenotypic AST assay for gonorrhea for a broader set of antibiotics," he added.

The current therapy for gonorrhea is a combination of two antibiotics — ceftriaxone paired with either azithromycin or doxycycline. But gonorrhea can also be susceptible to very old antibiotics, like tetracycline or penicillin, Coe said, "so the question is, can you find out rapidly, at the point of care, whether or not drugs that are older line can be used in place of our last-line drugs," he said.

The project is "fairly far along," and the funding will potentially take it to human studies, Coe said, with milestone funds available to support phenotypic susceptibility testing.

As previously reported, CARB-X, which stands for the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator, is a nonprofit partnership headquartered at Boston University comprising a portfolio of about 20 antibacterial products in clinical development.

CARB-X plans to invest $455 million in innovative antibiotics and other therapeutics, vaccines, rapid diagnostics, and devices to treat drug-resistant bacterial infections between 2016 to 2021. Funds come from the Biomedical Advanced Research and Development Authority (BARDA) and the Wellcome Trust, with in-kind support from the National Institute of Health's National Institute of Allergy and Infectious Diseases, and partners such as RTI International, the Broad Institute, MassBio, and the California Life Sciences Institute.

CARB-X recently awarded HelixBind funding to develop a bloodstream infection ID and AST assay, as well as funding to MicrobeDx for an ID and AST assay for a urinary tract infections.

In addition to the government grants and contracts, Talis is also privately funded by large private equity investors, Coe said, but he added that the firm is not able to publicly disclose its investors.