Microfluidic cytometric analysis of cancer cell transportability and invasiveness

Abstract

The extensive phenotypic and functional heterogeneity of cancer cells plays an important role in tumor progression and therapeutic resistance. Characterizing this heterogeneity and identifying invasive phenotype may provide possibility to improve chemotherapy treatment. By mimicking cancer cell perfusion through circulatory system in metastasis, we develop a unique microfluidic cytometry (MC) platform to separate cancer cells at high throughput, and further derive a physical parameter ‘transportability’ to characterize the ability to pass through micro-constrictions. The transportability is determined by cell stiffness and cell-surface frictional property, and can be used to probe tumor heterogeneity, discriminate more invasive phenotypes and correlate with biomarker expressions in breast cancer cells. Decreased cell stiffness and cell-surface frictional force leads to an increase in transportability and may be a feature of invasive cancer cells by promoting cell perfusion through narrow spaces in circulatory system. The MC-Chip provides a promising microfluidic platform for studying cell mechanics and transportability could be used as a novel marker for probing tumor heterogeneity and determining invasive phenotypes.

Correlating the viscoelasticity of breast cancer cells with their malignancy

“…Microwells ranged from 15 to 22 µm in diameter to accommodate the variety of sizes in each cell line. Microwell height was chosen to be 12 µm (smaller than reported average cell size [22]) to ensure adequate support for the cells as well as to ensure that the AFM tip will only be engaged with the cell and not the microwell. To fabricate microwells, we used a soft lithography technique to create master silicon with a series of cylindrical negative relief features.…”

Tumor-Initiating Cells: Emerging Biophysical Methods of Isolation

“…Several microfluidic platforms have been developed for this application. The platforms use diagonal ridges [110] or triangular posts [111] to force cells to deform as the flow through the channel. The cells deform to varying degrees depending on their elastic properties and travel differentially through the channels to different outlets.…”

Microfluidics as an Enabling Technology for Personalized Cancer Therapy

“…3) Microfluidics also enables more complex sorting mechanisms, including entirely label‐free approaches based on: imaging, cell deformability, size, and/or invasive features. A nice example for sorting on complex properties was shown by Liu et al, who developed a microfluidic chip in which cells are sorted based on the capacity of cells to travel through small constrictions (in between tilted microposts), as required for the formation of metastases. Their system has two unique features: one is the special geometry containing tilted microposts, which allow particle sorting based on the size; the other crucial feature is the rectangular microarray of 90 000 trapping barriers that mimic blood vessel diameter in order to trap cells.…”