Self-Assembled GO Honeycomb Microarray for Selective Cancer Cell Capture and Single Cell Analysis of Proteolytic Expression.

Abstract

Proteolytic enzymes expressed by circulating tumor cells are proved to facilitate their invasion into multiple organs via cleaving natural ECM networks, leading to consequent metastasis colonization and malignant lethality. Recent evidence suggests the rare metastasis initiating cells with higher proteolytic levels among circulating tumor cells (CTCs) may strongly increase the risk of metastasis. Beyond selective CTC capture, the heterogeneity in proteases expression provides a promising indicator for metastasis happening. To this end, the graphene oxide (GO) honeycomb microarray with single CTC matched sizes is fabricated via the self-assembly breath figure approach, which serves as an integrated protocol for selective CTC capture and single-cell analysis of protease activity. Contributing to synergistic effects of structure and chemistry, CTCs can be efficiently isolated and individually trapped in each honeycomb hole. Meanwhile, the crosstalk among CTCs can be erased by blocking direct cell-to-cell contact, which offers promising potentials in the single-cell analysis of protease expression. Integrating specific capture and in situ analysis of single CTCs on GO micropatterned surface is of significant importance in various biological and clinical applications such as cancer diagnostics and cancer therapeutic evaluation.