Automation of a Viscoelasticity Microcytometer for High-Throughput Biomechanical Phenotyping of Floating Cancer Cells

To date, microfluidics enables quantitative measurements of cell properties which have been difficult for the traditional cell research techniques. For instance, the biomechanical properties of floating cancer cells can be measured with multiple microfluidic techniques based on cell-solid or cell-flow interactions. The biomechanical properties have been proven of reflecting metastatic tendency and status of cancer cells; and therefore some of these characteristics, e.g. whole-cell stiffness, can be considered as the diagnostic biomarkers. In particular, cancer metastasis involves large deformation and migration of cancer cells from sites to sties through tiny tissue gaps and vessel walls; and hence the viscoelasticity properties of the cancer cells should take an important role. Considering that the effective identification of metastasis using the cancer patient’s blood is yet challenging, quantifying the viscoelasticity cell properties may provide additional information on the metastatic status and enhance the diagnostic precision and specificity for the related clinical applications.We propose to develop a fully automated microfluidic viscoelasticity microcytometer based on dynamic cell deformation along funnel-shaped confining microchannels. This microfluidic device is integrated with a computer-controlled system for achieving fully automated size and viscoelasticity quantification of every cell in a bio-sample. Technically, we first configure the device as multiple-stages of the confining microchannels with different dimensions. The nuclear elasticity and whole cell viscoelasticity properties can then be resolved from the cell movements along the confining channels, based on a Standard Linear Model together with the hyperelastic Tatara theories we developed previously. We design also cell focusing microstructure to ensure most (~100 %) cells in a biosample are quantified along the confining microchannels. The system automation includes elimination of imaging under a microscope. Instead, we adopt electrokinectic sensing via multiple groups of electrodes fabrication along the confining microchannels in order to achieve the full automation toward the translational research with clinical applications. The system automation also includes a biosample release module with a feedback control manner to realize the sequential single cell quantification, i.e. only one cell is detected along the confining channels at a time. Afterward, we optimize the system for the high detection throughput (>100 cells/min) by adjusting the key operation parameters of the system. Altogether, with further development the proposed fully automated viscoelasticity microcytometer can realize the high-throughput biomechanical phenotyping of floating cancer cells, offering additional cell characteristics for more promising cancer diagnosis as well as general cell/clinical analysis applications.