Real-time liquid biopsy

SOUTH SAN FRANCISCO, Calif.—Fluxion Biosciences Inc. hascome to an initial agreement to partner with Rubicon Genomics in a reagentsupply and collaboration program. The collaboration will integrate enrichmentmethods for rare cells using Fluxion's IsoFlux system with Rubicon's technologyfor the preparation and amplification of rare cell DNA or RNA using the RubiconNovaPLEX family of sample preparation kits.

Fluxion began working with Rubicon for amplification ingenomic analyses using the Rubicon PicoPlex single-cell, whole-genomeamplification kit. This product targets the pre-implantation geneticdiagnostics (PGD), cancer research and stem cell research markets, whichrequire rapid, reproducible amplification to profile patient genotypes,karyotypes and mutations. PicoPlex enables reference labs to begin qPCR,microarray or sequencing analysis less than three hours after collectingpatient cells. Specifically, the kit reproducibly amplifies total DNA onemillion-fold from single cells to produce five micrograms of amplified DNA inless than three hours. Next, Fluxion will use the Rubicon NovaPLEX family ofsample preparation kits for the circulating tumor cells (CTC) project. As partof this agreement, Fluxion and Rubicon will apply sample-specific products fromRubicon's amplification portfolio to samples processed by Fluxion's IsoFluxSystem. These amplified samples will then be optimal for analysis using avariety of genomics techniques, including NGS and PCR-based approaches.

Access to tumor tissue represents one of the mostsignificant challenges in characterizing specific cancers. CTCs disseminatefrom primary tumors and enter the peripheral bloodstream in very lowconcentrations. These rare circulating cells have shown promise as analternative to biopsies of primary tumor tissue, and can be used tocharacterize tumor status at the molecular level. However, many DNA analysismethods require higher amounts of genetic material than typically can be collectedfrom CTCs. Technologies developed by Fluxion and Rubicon provide forspecialized pre-analytical processing of difficult biological samples andenable subsequent analysis using sequencing, microarrays or PCR.

"Fluxion's IsoFlux system provides access to scarce cells,"with a real-time "liquid biopsy" that delivers high-quality CTC samplesoptimized for molecular analysis, says program director Michael Schwartz. Theplatform utilizes a proprietary microfluidic technology to isolate rare cellswith high efficiency.

"The system employs immuno-magnetic separation via beadsthat target antigens on the cell surface. We can use different markers toisolate different types of cells," Schwartz says.

Samples processed using the IsoFlux System are immediatelyready for downstream analysis. Multiple analytical techniques can be used withIsoFlux samples, including mutation detection, gene expression, sequencing andprotein analysis. The system provides much higher cell recovery rates, Schwartzstates.

"We control the flow path as it crosses the magnetic field,"he adds. "The result is fewer background cells and a high yield of cancercells. With other systems, it can be tough to remove cells from the substrate,but IsoFlux recovers 90 percent of the cells and moves them to downstreamapplications such as PCR, FISH, etc. Rubicon products are the gold standard fortesting for aneuploidies and mutations in single human cells, and fordifferential gene expression in formalin-fixed surgical samples. The Rubicon protocolsare simpler, faster and more robust than the competition, and they also yieldsuperior analytical results on sequencing, array and PCR platforms."

Rubicon's core competency is the creation of more efficientmolecular biology tools for genetic, epigenetic and expression analysis ofdifficult clinical samples to facilitate gene-based research, drug development,diagnostics and forensics. James Koziarz, the company's CEO, notes that,"Partnering with innovators such as Fluxion is a key element of our strategyfor increasing access to our pre-analytical technologies for improving theanalysis of DNA and RNA from challenging samples. We look forward tocollaborating with Fluxion in the emerging and important field of circulatingtumor cell analysis."

Privately held Rubicon is located in Ann Arbor, Mich.