Tandem microfluidic chip isolation of prostate and breast cancer cells from simulated liquid biopsies using CD71 as an affinity ligand

Abstract

The use of blood as a liquid biopsy provides a minimally invasive and less traumatic approach for initial cancer screens as well as patient monitoring. However, current clinical protocols require a priori knowledge of cancer type for liquid biopsy analyses. Previously, we proposed the use of the human transferrin 1 receptor protein (CD71) as a universal capture target for cancer cells analyses. In this study we have attempted to identify the lowest limit of detection for circulating tumor cells of prostate (PC-3) and breast cancers (MDA-MB-231) using CD71. We used a novel high-throughput herringbone chip design which could extract PC-3 cells at 34 ± 5% purity and MDA-MB-231 cells at 43 ± 35% purity when spiked to lysed blood at 0.1%. MDA-MB-231 cell spiked samples showed higher standard deviation, but the system captured 55 ± 16 cells, which is a sufficient number of cells for subsequent analyses. Further, this herringbone chip design has been shown to be compatible with an erythrocyte lysis chip we have described in previous studies. This circuit was capable of capturing 510 ± 120 cells with a purity of 82 ± 14% using <7 μL of a whole blood sample spiked with 10% MDA-MB-231 cells. Using an erythrocyte lysis circuit eliminates the need for human intervention for target cell enrichment, thereby reducing cell loss and sample contamination. We have shown that, when used with the high-throughput herringbone chip CD71 has the capacity to sensitively detect rare target cells for routine low-cost cancer screens.