Microfluidic Magnetic Anisotropic Array for High-throughput Isolation of Extracellular Vesicles and Exosomes

ABSTRACT Tumor derived circulating exosomes has been emerging in fundamental cancer researchclinical diagnosis and monitoring of treatment responsesHoweverthe specific preparation of enricheddistinct exosome populations is still challengingCurrentlythe most common procedure for purifying exosomes involves a series of high speed ultracentrifugation steps in order to remove cell debris and pellet exosomesCommercially available exosome isolation kits still need a benchtop centrifuge before the chemical precipitation of exosomal molecular contentsThe isolation protocols are tedious and time consuminghwith relatively low yield and recovery purityIn order to substantially improve isolation performance and throughputClara Diagnostics Incproposes to develop a microfluidic based isolation platform as a research tool for automatedhigh specific and high throughput processing of tumor exosomes and subtypes from a wide variety of biofluidsin response to NIH PASBIR Phase I Funding OpportunityCurrentlythere is no any microfluidic based exosome isolation platform commercially availablealthough microfluidic technology has proved unmatched capability for exosome processing and molecular profilingClara Diagnostics Incaims to fulfill this gap by developing the first microdevice product which enables the automatedhigh throughput and continuous processing ofsamples on demandThe implementation of magnetic anisotropic oscillation inchannel microfluidic device enables ultra fast mixing of beads with biofluids while using high flow ratesThe single channel processing speed isL min with a throughput ofchannelsNote that conventional ultracentrifugation or differential centrifugation processes total blood plasma volume ofmL inh orsamples per runOur proposed platform can processsamples with total processing volume ofmL inhwhich isfold increaseTogether with the high throughput operation and high specificity to tumorexosomes and subtypeswe will deliver a genericenabling platform for preparing enricheddistinct exosome subpopulations from a wide variety of biofluidssuch as blood serumplasmaurinesalivacell culture mediummalignant ascitesand milkThis product as a research tool can process sample volumes fromchannels in microliter for on chip analysis to milliliter preparation for variable downstream benchtop measurements and therapeutic applicationse gmass spectrometryPCRand sequencingand delivery carrierIn strong contrast to current commercial exosome isolation kitsthe proposed microfluidic platform will present a new generation of product that offers unmatched sample processing capabilities for exosome research and immensely accelerates cancer research and clinical development of liquid biopsy RELEVANCE TO PUBLIC HEALTH The utility of exosomesparticularly tumor derived circulating exosomesis pressingly necessary to fundamental cancer researchclinical diagnosis and monitoring of treatment responsesClara Diagnostic Inchas strived to deliver a robustness and ease of use research tool for efficient exosome isolation from variable body fluidsultimately advancing exosomes cancer research