Development of an Integrated Microfluidic-Based System for Single Cell Mutation Analysis and Drug Sensitivity Test of Circulating Tumor Cells/Cell Clusters
DescriptionCancer cells from solid tumors can disseminate into bloodstream and circulate either as single migratory circulating tumor cells (CTCs) or as multicellular clusters (CTC clusters) with highly metastatic ability. Technologies for detection, isolation and analysis of CTCs and CTC clusters will enable a broad range of clinical applications including prediction of 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 may also reveal the heterogeneity in metastatic tumors for precise selection of target-based drugs. However, there is a lack of techniques for capturing CTCs and CTC clusters from blood or other bodily fluids (such as plural fluid or ascites), for isolating single tumor cells from CTC and CTC clusters, and for analyzing target mutations and drug sensitivities. In our previous research and preliminary experiments, we have demonstrated the feasibility of using microfluidics to seize cells and cell clusters, to separate individual cells, and to carry out single cell mutation analysis. In this project, we propose to develop an integrated microfluidic system for capturing, isolating, and culturing single tumor cells from CTCs and CTC clusters for mutation analysis and drug sensitivity test at single cell level. Specifically, we will design and optimize three individual microfluidic modules, each with the functions of trapping and releasing CTCs and CTC clusters by varying gap dimensions in the channel and controlling flow directions, isolating single tumor cells from captured CTCs and CTC clusters by microvalves and filtering out non-cancerous cells, and testing dose-dependent response of anti-tumor drugs on single cells cultured in microwells, respectively. We will also integrate the three modules into one single platform once they are optimized and validated. The microfluidic system will provide an important tool for quantitative identification and analysis of CTCs and CTC clusters at single cell level, which will enable more precise clinical decision in treating cancer, and better understanding of the roles of CTCs and CTC clusters and intra-tumor heterogeneity in progression and metastasis of solid tumors.
|Effective start/end date||1/01/17 → …|
- microfluidics , circulating tumor cells , CTC cluster , single cell analysis , cancer therapy