Detection and Control of Air Liquid Interface with an Open-Channel Microfluidic Chip for Circulating Tumor Cells Isolation from Human Whole Blood

Abstract

We have proposed a bio-automation system to isolate and recover circulating tumor cells (CTCs) individually from whole blood. An open-channel microfluidic chip-based approach is used to isolate the CTCs. The proposed microfluidic chip design can form a stable air-liquid interface. CTCs are trapped by the gaps in between the pillars of the microfluidic chip due to capillary force associated with the meniscus of the air-liquid interface. We propose a chip design to stabilize air-liquid interface and sample flow speed. We introduce an image analysis algorithm to detect the position of the air-liquid interface. Using the visual feedback from the image analysis algorithm, a control system is proposed to control air-liquid interface position. We succeeded in stabilizing the flow speed, making it feasible for the isolation of 5 mL of whole blood to be completed within 30 min. We achieved an average of position error of air-liquid interface of 4 μm with standard deviation of 7 μm. We have confirmed that air-liquid interface position is a deciding factor for trapping area of CTCs. By controlling air-liquid interface position, we have achieved trapping CTCs in a narrow band with a high concentration.