A Fully Automated and Integrated Microfluidic System for Efficient CTC Detection and Its Application in Hepatocellular Carcinoma Screening and Prognosis

ACS Appl Mater Interfaces. 2021 Jun 30;13(25):30174-30186. doi: 10.1021/acsami.1c06337. Epub 2021 Jun 18.

Abstract

Analysis of circulating tumor cells (CTCs) is regarded as a useful diagnostic index to monitor tumor development and guide precision medicine. Although the immunoassay is a common strategy for CTC identification and heterogeneity characterization, it is challenged by poor reaction efficiency and laborious manipulations in microdevices, which hinder the sensitivity, throughput, simplification, and applicability. To meet the need for rapid, sensitive, and simple CTC analysis, we developed an efficient CTC detection system by integrating a 3D printed off-chip multisource reagent platform, a bubble retainer, and a single CTC capture microchip, which can achieve CTC capture and identification within 90 min. Compared with traditional CTC identification methods, this system decreases immunostaining time and antibody consumption by 90% and performs the on-chip immunoassay in a fully automated manner. Using this system, CTCs from the peripheral blood of 19 patients with various cancers were captured, detected, and compared with clinical data. The system shows great potential for early screening, real-time monitoring, and precision medicine for hepatocellular carcinoma (HCC). With the advantages of automation, stability, economy, and user-friendly operation, the proposed system is promising for clinical scenarios.

Keywords: automated microfluidic input; circulating tumor cells; hepatocellular carcinoma; on-chip immunoassay; pressurization driving.

MeSH terms

  • Carcinoma, Hepatocellular / diagnosis*
  • Cell Separation / instrumentation*
  • Early Detection of Cancer / instrumentation
  • Equipment Design
  • HCT116 Cells
  • Humans
  • Immunoassay / instrumentation
  • Liver Neoplasms / diagnosis*
  • Microfluidic Analytical Techniques / instrumentation*
  • Neoplastic Cells, Circulating / pathology*
  • Prognosis