Parallelized Cell Isolation in a Well Plate Format using Ratcheting Cytometry

Project Summary Treatment of immunological disorders with emerging treatments such as immunotherapy represent a growing medical paradigmTo create potent and targeted therapiesdefining the underlying immunological mechanisms of action and is criticalBecause of immunological complexitymeasurements across multiple immune populations are essential as both diseases and treatments are often driven by several subpopulations of cellsHoweverdue to limitations with current cell isolation and analysis toolsprecisely mapping these multi population interactions is difficult and cost prohibitive to deploy at a scale conducive for high throughput target discovery or streamlined clinical monitoringMost high precision cell isolation and analysis toolssuch as FACS or microfluidic platformsare too low throughput and are difficult to integrate into SBS formats for high throughput screeningHTSworkflowsContrastinglybulk cell sorting methods such as MACS are easily integrated into HTS formats but still have limited parallelizationhigh sample consumptionand poor performance with rare cell typesThe inherent tradeoff of precision and scalability impedes immunological Randamp D and clinical translation effortsThrough primary market research interviews using I Corp techniquesresearchers have voiced their dissatisfaction with the current cell isolation tools saying they are amajor roadblock in our work on phenotypic analysisWe reasoned that a product that can highly parallelized and efficient cell purification in an SBS well plate format would alleviate these bottlenecks and accelerate clinical translationLeveraging a core technology known as ratcheting cytometrythe objective of this proposal to develop asmart platewhich can achieve integrated cell purification in awell plate formatIn preliminary studiesratcheting cytometry has demonstrated quantitative cell sorting capacity and capacity to self assemble cells into a single cell formatIn phase Iratcheting cytometry will be compared to the gold standard of MACS in isolating CDmonocytesIn parallela scaled ratcheting cytometry instrument will be developed to accommodate whole well plate formatsFinallya prototype ratcheting cytometry smart plate will be developed and tested on the scaled instrumentPhase II will focus on developing a repeatable smart plate design with established QC metrics and instrument integration with robotic fluid handlers Project Narrative The goal of this project is to develop a smart well plate with integrated cell purification capabilitiesCurrent technologies cannot balance high purity enrichment and scalability which impedes immunological Randamp D and clinical translationOur platform can provide an integrated approach to multi population cell analysis in established lab automation architectures