Microfluidic iterative mechanical characteristics (iMECH) analyzer for single-cell metastatic identification

Abstract

This study describes the development of a microfluidic biosensor called the iterative mechanical characteristics (iMECH) analyzer which enables label-free biomechanical profiling of individual cells for distinction between metastatic and non-metastatic human mammary cell lines. Previous results have demonstrated that pulsed mechanical nanoindentation can modulate the biomechanics of cells resulting in distinctly different biomechanical responses in metastatic and non-metastatic cell lines. The iMECH analyzer aims to move this concept into a microfluidic, clinically more relevant platform. The iMECH analyzer directs a cyclic deformation regimen by pulling cells through a test channel comprised of narrow deformation channels and interspersed with wider relaxation regions which together simulate a dynamic microenvironment. The results of the iMECH analysis of human breast cell lines revealed that cyclic deformations produce a resistance in non-metastatic 184A1 and MCF10A cells as determined by a drop in their average velocity in the iterative deformation channels after each relaxation. In contrast, metastatic MDA-MB-231 and MDA-MB-468 cells exhibit a loss of resistance as measured by a velocity raise after each relaxation. These distinctive modulatory mechanical responses of normal-like non-metastatic and metastatic cancer breast cells to the pulsed indentation paradigm provide a unique bio-signature. The iMECH analyzer represents a diagnostic microchip advance for discriminating metastatic cancer at the single-cell level.