High-porosity thin membrane for high-efficiency capture of rare cells

Abstract

High efficiency capture of rare cells such as circulating tumor cells (CTCs) in the blood of cancer-patient is challenging for size-based separation methods, because of the heterogeneity of the cells, the presence of a huge number of background cells (red and white blood cells), and the overlap in size of the rare cells and some of the background cells. In this work, we developed a systematic study to evaluate the parametric dependence of rare cell capture efficiency by using model cells. High-porosity and thin membranes with supporting honeycomb microframe are fabricated by using a two-level lithography technique. They are then integrated into a microfluidic device for real-time monitoring of flow-induced transmembrane pressure with a solution with or without cells. Our results show both experimentally and theoretically a great importance of the pore number of the membrane and the flow rate. When more than 80% of pores are clogged by large background cells, the rare cell capture efficiency decreases significantly. Otherwise, a lossless capture is theoretically achievable with a high-porosity and large-area membrane under optimal flow conditions.