High Density Array Digital PCR for Cancer Rare Mutation Quantification

AbstractFor the PhaseSBIR projectCOMBiNATi is looking to prove the feasibility of an injection moldedk array digital PCR consumable for KRAS GR cancer rare mutation quantification analysisDigital PCRdPCRhas drawn attentions in both cancer genomic research and clinical research communities for its ability to detect rare eventshigh sensitivityless prone to inhibitionhigh specificityno need for an internal standardhigh precisionand access to well developed PCR reagentsEnvisioned applications enabled by dPCR in cancer translational research and clinical applications includeMutation guided prescription of cancer drugs for improved efficacyLiquid biopsy with cell free nucleic acids for continuous therapeutic monitoringHowevercurrent dPCR platforms are slow to overtake the gold standard qPCRdespite its superior performance in rare mutation detectionmainly because the cost of consumables is highand the workflow is complicatedOur vision is to develop an entry level turnkey dPCR platform to allow load walkaway workflow and the best in class combination of cost per sampleand performance per experimentaccelerating the transition from qPCR to dPCR in the cancer research communityThemonth PhaseSBIR project will allow COMBiNATi to complete the feasibility of the following key value hypothesiswhich will serve as the new product design spec for Phaseplatform development effortHigh sensitivitymutation to wildtypedetection limitSingle workflowReagent partitioningthermal cycling and image acquisition in one systemOpen platformOff the shelf PCR reagents are compatible with the platform without purchasingof additional reagents from COMBiNATi NarrativeThere are increasing evidences showing that nucleic acids could complement proteins as additional biomarkers when it comes to cancer prognosisdiagnosisas well as therapeutics efficacy monitoringCombinati is developing a precision nucleic acid quantification platform building on its unique consumable technology in the hope to accelerate the adoption of digital PCRdPCRin the cancer genomic research marketin academicindustrial and clinical settingsOur goal is to accelerate its transition from benchtop to bedsideWith the help from this PhaseSBIR projectwe will prove the feasibility of the injection molded consumable for rare mutation detection with walkaway operationas well as an open platform with standard qPCR reagents