A Multifunctional Double-Array Petals Flower-Shaped Microfluidic Chip Combining Affinity and Physical Properties in Isolation of CTCs.

Circulating tumor cells (CTCs) are tumor cells that break away from the origin tumors and disseminate in the bloodstream and lymphatic circulation systems. CTCs originate from the original tumor with a similar bimolecular source. This makes CTCs play a vital status in cancer prognosis and diagnosis. However, CTC separation is highly challenging due to rarity and heterogeneity. In the present work, we designed a double-array petal flower-shaped microfluidic chip, a multifunctional capturing and isolation chip combining affinity and physical properties. The chip is composed of three arrays of microfluidic barriers organized one after the other. For the first array, six convex structures are set in each narrow channel. The first structure has a total of 12 such channels, which can increase collision frequency between cancer cells and convex structures in the channel. The second capture structure is one composed of an S-shaped array of concave triangle microcolumns and parabolic circular microcolumns. The advantage of this setting is that it can capture CTCs in the blood flowing into the first structure in 12 directions from multiple angles and multiple times, so as to improve capture efficiency. The third capture structure is composed of elliptical microposts and cylinders. The treated blood is captured for the last time. Because of the round or elliptical shape, it can retain the cell viability to a great extent, which is convenient for later pathological analysis of tumor cells. Simulation of velocity influence, pressure effects, streamline tendency, and shear rates is carried out for each structure. Therefore, theoretical validation has been illustrated to achieve high capture rate and purity. These delicate designs and numerical analysis clarify feasibility for further experiments of CTC enumeration, clinical analysis, and evaluation of cancer therapy.