Design and numerical simulation analysis of three multifunctional microfluidic chips in isolation of CTCs

Abstract

Circulating tumor cells (CTCs) are tumor cells that dissociate from the origin tumors and disseminate in the bloodstream and lymphatic circulation systems. CTCs carry a remarkably similar constituent to the original tumor, which makes CTCs have a significant value in the biological molecular analysis of cancer. However, CTCs are extremely rare and heterogeneous in blood. Therefore, CTC separation is highly challenging. In the present work, we designed a fan-shaped symmetric microfluidic chip, a multifunctional capturing and co-culture chip, and an immunomagnetic chip in isolation of CTCs. The first chip is composed of two-faced fans placed symmetrically. Inside, there are arc-shaped arrays composed of numerable circular microposts. CTCs could be captured by antibody-modified microposts, and blood constituents flow away. Pressure, velocity, streamline, and shear stress simulations were performed theoretically. The second chip is a multifunctional capturing and co-culture chip. Patient blood samples are filtered by a W-shaped structure, and isolated viable CTCs could co-culture with several normal cells of the same type to mimic the real microenvironment. The third microfluidic chip is a combination of both immunomagnetic and physical-based. Many electronic coils are wound around the chip to produce a strong magnetic field when electrified. CTCs are incubated with magnetic beads. Magnetized CTCs would be oriented to be enriched. Those CTCs without conjugating beads would be captured by two interlace arrays of square microposts. These three delicate designs and theoretical explanation clarify feasibility for further experiments of CTC enumeration, clinical analysis, and evaluation of cancer therapy.