Project Grant R44CA287952

AN INTEGRATED MICROFLUIDIC DEVICE FOR PATIENT-DERIVED MICRO-ORGANOSPHERES - PROJECT SUMMARY/ABSTRACT FUNCTIONAL PRECISION ONCOLOGY HOLDS GREAT POTENTIAL TO IMPROVE THE CURRENT CLINICAL PARADIGM BY USING PATIENT- DERIVED EX VIVO SYSTEMS (E.G., PDXS AND ORGANOIDS) FOR PERSONALIZED TREATMENT-SPECIFIC READOUTS. HOWEVER, PRESENTLY, THESE MODELS TAKE LONG TO ESTABLISH, ARE NOT SCALABLE AND ARE COSTLY; SUCH CHALLENGES IMPEDE THEIR WIDE-SPREAD APPLICABILITY AND COMMERCIAL POTENTIAL. THEREFORE, THERE REMAINS AN UNMET NEED TO DEVELOP NOVEL FUNCTIONAL PRECISION MEDICINE STRATEGIES THAT PAIR THE RIGHT THERAPY TO EACH PATIENT TO IMPROVE CLINICAL OUTCOMES. XILIS IS ANSWERING THIS CALL BY DEVELOPING A NOVEL FDA, CLIA AND IVDR-COMPLIANT MEDICAL DEVICE THAT CAN RAPIDLY GROW MICRO-ORGANOSPHERES (MOS) - HIGH-FIDELITY, EX VIVO PATIENT AVATARS. XILIS HAS DEVELOPED A PROPRIETARY BENCHTOP MOS GENERATOR INSTRUMENT (MOSGEN) TO GENERATE MOS BASED ON THE FOLLOWING PROCESSES: 1) FORMATION OF MATRIGEL DROPLET-BASED MOS "MICRO-REACTORS" IN OIL EMULSIONS FROM LOW VOLUME CLINICAL SAMPLES (E.G., 18G BIOPSIES) 2) POLYMERIZATION OF THE MATRIGEL VIA HEAT THROUGH OUR UNIQUE CHIP DESIGN, 3) SAMPLE DEMULSIFICATION USING OUR PROPRIETARY PROCESS, WHERE THE OIL IS REMOVED, AND THE DROPLETS ARE RESUSPENDED IN MEDIA FOR DOWNSTREAM ESTABLISHMENT. ALTHOUGH FUNCTIONAL, THE CURRENT MOSGEN PROTOTYPE HAS DISPARATE, STAND- ALONE WORKFLOWS FOR MOS FORMATION, POLYMERIZATION AND DEMULSIFICATION THAT NEED COMPLEX TUBING, COMPLICATED USER INTERACTION, AND REQUIRES LENGTHY DISINFECTION PROCEDURES, WHICH IMPEDES ITS USE AND APPLICABILITY IN CLINICAL WORKFLOWS. THUS, IN THIS SBIR FAST-TRACK, OUR MULTI-DISCIPLINARY TEAM WITH ENGINEERING, BIOLOGICAL AND CLINICAL EXPERTISE WILL BUILD AN AUTOMATED, END-TO-END, COMMERCIAL-GRADE MOSGEN INSTRUMENT THAT RAPIDLY GENERATES MOS IN A SCALABLE AND REPRODUCIBLE MANNER WITH MINIMAL RISK OF CONTAMINATION. XILIS CURRENTLY IS ENGAGED WITH ITS STRATEGIC PARTNER, MD ANDERSON CANCER CENTER, AND WILL IMPLEMENT THE MOSGEN INTO THE EXISTING CLINICAL WORKFLOW TO VALIDATE ITS OPERATION. SBIR FUNDING WOULD ALSO BOLSTER XILIS' COLLABORATION WITH MAYO CLINIC TO ENABLE DEVICE VALIDATION BY SUPPORTING THE NCI-FUNDED BEAUTY CLINICAL TRIALS. IN PHASE I, WE WILL DEVELOP A PENULTIMATE PROTOTYPE OF OUR MOSGEN INSTRUMENT, WHICH WILL INTEGRATE THE HARDWARE AND SOFTWARE WORKFLOWS. WE HAVE ENGINEERED A SERIES OF NOVEL SERPENTINE MICROFLUIDIC CHIPSETS, WHICH WE WILL INTEGRATE INTO OUR INSTRUMENT FOR AN ALL-IN-ONE SOLUTION. WE WILL TEST THE PROTOTYPE USING COLORECTAL CANCER SAMPLES (LEVERAGING OUR REGISTERED CLINICAL TRIAL WITH LEADING SITE, MD ANDERSON) AND MULTIPLE MYELOMA SAMPLES (FROM OUR COLLABORATION WITH DUKE UNIVERSITY). IN PHASE II, WE WILL BUILD OUR END-TO-END, COMMERCIAL-GRADE MOSGEN, IN COMPLIANCE WITH FDA'S QSR PART 320. THIS INSTRUMENT WILL BE AUTOMATED AND EASY-TO-USE, TO READILY SUPPORT SEAMLESS IMPLEMENTATION INTO CURRENT CLINICAL WORKFLOWS. TO TEST THE MOSGEN, WE WILL PARTNER WILL MD ANDERSON AND MAYO CLINIC (SUBAWARD) AND INTEGRATE OUR INSTRUMENT INTO EXISTING CLINICAL TRIALS TO VALIDATE ITS OPERATION. SUCCESSFUL COMPLETION WILL SUPPORT THE DEVELOPMENT OF A COMMERCIAL, FULLY-AUTOMATED, COMMERCIAL-GRADE MICROFLUIDIC INSTRUMENT THAT CAN STREAMLINE THE GENERATION OF MOS TO ENABLE ROBUST FUNCTIONAL PRECISION MEDICINE CAPABILITIES.