FAST: Size-Selective, Clog-Free Isolation of Rare Cancer Cells from Whole Blood at a Liquid–Liquid Interface

TLDR

Circulating tumor cells (CTCs) can enable minimally invasive early detection of metastasis and treatment monitoring, yet current enrichment methods are complex and time‑consuming, and size‑based isolation suffers from clogging and suboptimal recovery and purity. This study aims to develop a clog‑free, highly sensitive, rapid, and label‑free isolation of viable CTCs from whole blood using a stand‑alone lab‑on‑a‑disc system called FAST. FAST employs fluid‑assisted separation technology inspired by antifouling membranes, achieving 95.9 % recovery, >2.5‑log white blood cell depletion, and flow rates >3 mL/min without prior sample treatment. Simulations and experiments confirm uniform, clog‑free enrichment with pressure drops below 1 kPa, and clinical testing on 142 breast, stomach, or lung cancer patients demonstrates point‑of‑care detection capability.

Abstract

Circulating tumor cells (CTCs) have great potential to provide minimally invasive ways for the early detection of cancer metastasis and for the response monitoring of various cancer treatments. Despite the clinical importance and progress of CTC-based cancer diagnostics, most of the current methods of enriching CTCs are difficult to implement in general hospital settings due to complex and time-consuming protocols. Among existing technologies, size-based isolation methods provide antibody-independent, relatively simple, and high throughput protocols. However, the clogging issues and lower than desired recovery rates and purity are the key challenges. In this work, inspired by antifouling membranes with liquid-filled pores in nature, clog-free, highly sensitive (95.9 ± 3.1% recovery rate), selective (>2.5 log depletion of white blood cells), rapid (>3 mL/min), and label-free isolation of viable CTCs from whole blood without prior sample treatment is achieved using a stand-alone lab-on-a-disc system equipped with fluid-assisted separation technology (FAST). Numerical simulation and experiments show that this method provides uniform, clog-free, ultrafast cell enrichment with pressure drops much less than in conventional size-based filtration, at 1 kPa. We demonstrate the clinical utility of the point-of-care detection of CTCs with samples taken from 142 patients suffering from breast, stomach, or lung cancer.