A multiplex platform based on cellular barcoding for measuring single cell drug susceptibility

Abstract

Predicting individual patient response to cancer drugs has been challenging. As many anticancer drugs aim to modulate cell deaths or growth inhibition, a useful assay for drug susceptibility would require direct assessment of phenotypic changes to cells upon drug treatment, such as cell viability or growth rate. Previously, the serial microfluidic mass sensor arrays have been used to measure single-cell mass accumulation rates over ~20 minute intervals to assess drug susceptibility. Here, we present a multiplexing platform that allows evaluation of multiple drug response conditions in a single experiment by utilizing fluorescent barcodes based on cell surface labeling. Fluorescence microscopy was integrated with the serial microfluidic mass sensor arrays to match a given barcode (which corresponds to a drug condition) with its mass accumulation rate as each cell flows through the microfluidic channel. To validate our approach, we show that the dynamics of drug response can be obtained from a single experiment by multiplexing drug treatment durations. Our validation highlights the capability of our platform to both eliminate measurement bias due to time differences in drug exposure and reduce the operation time when compared to standard time point assays.