Separable bilayer microfiltration device for viable label-free enrichment of circulating tumor cells

Abstract

We designed a new separable bilayer (SB) microfiltration device for the viable enrichment of circulating tumor cells (CTCs) independent of antigen expression. Bilayer pore structures at the micro scale decrease cell damage to preserve viability, while maintaining throughput to allow rapid enrichment. The large pore size (40 um) of the upper layer facilitates the CTCs proliferation on chip. The separability enables the efficient release of the CTCs after successful on chip culture of captured CTCs. We characterized the device performances including capture efficiency, enrichment against leukocytes, viability and proliferability. The SB device can enrich tumor cells with 80% capture efficiency, higher than 10^3 enrichment, and better than 70% viability from 1 mL whole blood samples on a 1 cm^2 device. Multiple cell lines were shown to be able to proliferate after captured on SB device. Furthermore, using CTCs derived from an in vivo model system, cell cultures were established by releasing the captured CTCs from the chip. The cultured CTCs and their corresponding parental cell lines were injected into mice. Tumors were established with no discernable differences in volume and rate of growth, demonstrating similar tumorigenicity of viable CTCs recovered by the SB device. In a feasibility study, we successfully detected CTCs from 1 mL of clinical whole blood sample enriched via SB device.

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