A Mechanophenotyping chip for high-throughput detection of metastatic bacteria-infected circulating tumor cells.

Abstract

Emerging evidence underscores biophysical characteristics of cancer cells as key modulators of cancer progression and metastasis. Herein, we reported a cell-mechanophenotyping screening microfluidic chip (termed LesM) for the high-efficient capture of circulating tumor cells (CTCs) and evaluation of single-cell deformation to reveal the hematogenous metastatic potential of bacteria-infected breast cancer. LesM employs L-shaped traps to capture single cells, leveraging bacteria-infected CTCs with cytoskeletal reorganization traverse narrowed channels while rigid native cells are retained. The platform demonstrates an average single-cell capture efficiency of 95.42% and specificity of 85.34% in discriminating infected versus non-infected breast cancer cells, validated through parallel in vivo metastatic assays. LesM enables high-throughput sensing up to 10,240 cells of mechanical signatures and microbial cargo, correlating with metastatic risk and antibiotic response. By bridging biomechanics and intratumoral microbiota detection, LesM offers a transformative liquid biopsy tool for predicting distant metastasis and guiding antimicrobial therapies in bacteria-infected breast cancers.