Portable Filter-Based Microdevice for Detection and Characterization of Circulating Tumor Cells

TLDR

Sensitive detection and characterization of circulating tumor cells could transform cancer care, yet current methods suffer from limited capture efficiency and inadequate characterization. The authors developed a portable parylene‑membrane filter microdevice that isolates CTCs by size with high recovery and performs direct on‑chip imaging and genetic analysis, and they evaluated its sensitivity using spiked blood samples. The device was tested on 59 model‑system samples to determine its recovery rate, achieving over 90 % recovery with a 95 % probability of detecting at least one cell when five are seeded in 7.5 mL of blood. In 57 patient samples, the microdevice identified CTCs in 51 patients versus 26 with the CellSearch platform, and when both methods detected CTCs it recovered higher numbers in all but five patients, underscoring its potential for routine clinical CTC analysis.

Abstract

Sensitive detection and characterization of circulating tumor cells (CTC) could revolutionize the approach to patients with early-stage and metastatic cancer. The current methodologies have significant limitations, including limited capture efficiency and ability to characterize captured cells. Here, we report the development of a novel parylene membrane filter-based portable microdevice for size-based isolation with high recovery rate and direct on-chip characterization of captured CTC from human peripheral blood.We evaluated the sensitivity and efficiency of CTC capture in a model system using blood samples from healthy donors spiked with tumor cell lines. Fifty-nine model system samples were tested to determine the recovery rate of the microdevice. Moreover, 10 model system samples and 57 blood samples from cancer patients were subjected to both membrane microfilter device and CellSearch platform enumeration for direct comparison.Using the model system, the microdevice achieved >90% recovery with probability of 95% recovering at least one cell when five are seeded in 7.5 mL of blood. CTCs were identified in 51 of 57 patients using the microdevice, compared with only 26 patients with the CellSearch method. When CTCs were detected by both methods, greater numbers were recovered by the microfilter device in all but five patients.This filter-based microdevice is both a capture and analysis platform, capable of multiplexed imaging and genetic analysis. The microdevice presented here has the potential to enable routine CTC analysis in the clinical setting for the effective management of cancer patients.