Development of an Integrated Microfluidic-Based System for Single Cell Mutation Analysis and Drug Sensitivity Test of Circulating Tumor Cells/Cell Clusters

Project: Research

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Description

Cancer cells from solid tumors can disseminate into bloodstream and circulate either assingle migratory circulating tumor cells (CTCs) or as multicellular clusters (CTC clusters)with highly metastatic ability. Technologies for detection, isolation and analysis of CTCsand CTC clusters will enable a broad range of clinical applications including predictionof drug response, monitoring of treatment outcomes, and early detection of recurrence.DNA mutation analysis of drug targets on single cells from CTCs and CTC clusters mayalso reveal the heterogeneity in metastatic tumors for precise selection of target-baseddrugs. However, there is a lack of techniques for capturing CTCs and CTC clusters fromblood or other bodily fluids (such as plural fluid or ascites), for isolating single tumorcells from CTC and CTC clusters, and for analyzing target mutations and drugsensitivities. In our previous research and preliminary experiments, we havedemonstrated the feasibility of using microfluidics to seize cells and cell clusters, toseparate individual cells, and to carry out single cell mutation analysis. In this project,we propose to develop an integrated microfluidic system for capturing, isolating, andculturing single tumor cells from CTCs and CTC clusters for mutation analysis and drugsensitivity test at single cell level. Specifically, we will design and optimize threeindividual microfluidic modules, each with the functions of trapping and releasing CTCsand CTC clusters by varying gap dimensions in the channel and controlling flowdirections, isolating single tumor cells from captured CTCs and CTC clusters bymicrovalves and filtering out non-cancerous cells, and testing dose-dependent responseof anti-tumor drugs on single cells cultured in microwells, respectively. We will alsointegrate the three modules into one single platform once they are optimized andvalidated. The microfluidic system will provide an important tool for quantitativeidentification and analysis of CTCs and CTC clusters at single cell level, which willenable more precise clinical decision in treating cancer, and better understanding of theroles of CTCs and CTC clusters and intra-tumor heterogeneity in progression andmetastasis of solid tumors.

Detail(s)

Project number9042390
Grant typeGRF
StatusFinished
Effective start/end date1/01/1723/12/20

    Research areas

  • microfluidics , circulating tumor cells , CTC cluster , single cell analysis , cancer therapy