Tapered-slit membrane filters for high-throughput viable circulating tumor cell isolation

Abstract

This paper presents tapered-slit membrane filters for high-throughput viable circulating tumor cell (CTC) isolation. The membrane filter with a 2D array of vertical tapered slits with a gap that is wide at the entrance and gradually decreases with depth, provide minimal cell stress and reduce 82.14 % of the stress generated in conventional straight-hole filters. We designed two types of tapered-slit filters, Filters 6 and 8, respectively, containing the tapered slits with outlet widths of 6 mu m and 8 mu m at a slit density of 34,445/cm(2) on the membrane. We fabricated the vertical slits with a tapered angle of 2 degrees on a SU8 membrane by adjusting the UV expose dose and the air gap between the membrane and the photomask during lithography. In the experimental study, the proposed tapered- slit filter captured 89.87 % and 82.44 % of the cancer cells spiked in phosphate buffered saline (PBS) and diluted blood (blood: PBS=1:4), respectively, at a sample flow rate of 5 ml per hour, which is 33.3 times faster than previous lateral tapered- slit filters. We further verified the capability to culture on chip after capturing: 72.33 % of cells among the captured cells still remained viable after a 5-day culture. The proposed tapered- slit membrane filters verified high-throughput viable CTC isolation capability, thereby inaugurating further advanced CTC research for cancer diagnosis and prognosis.