Open AccessSystem Modularity Chip for Analysis of Rare Targets (SMART-Chip): Liquid Biopsy Samples
Author(s) -
Thilanga N. Pahattuge,
Ian M. Freed,
Mateusz L. Hupert,
Swarnagowri Vaidyanathan,
Katie Childers,
Małgorzata A. Witek,
Kumuditha M. Weerakoon-Ratnayake,
Daniel Park,
Anup Kasi,
Mazin F. Alkasspooles,
Michael C. Murphy,
Steven A. Soper
Publication year - 2021
Publication title -
acs sensors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.055
H-Index - 57
ISSN - 2379-3694
DOI - 10.1021/acssensors.0c02728
Subject(s) - circulating tumor cell , liquid biopsy , computer science , embedded system , cancer , medicine , metastasis
Liquid biopsies are becoming popular for managing a variety of diseases due to the minimally invasive nature of their acquisition, thus potentially providing better outcomes for patients. Circulating tumor cells (CTCs) are among the many different biomarkers secured from a liquid biopsy, and a number of efficient platforms for their isolation and enrichment from blood have been reported. However, many of these platforms require manual sample handling, which can generate difficulties when translating CTC assays into the clinic due to potential sample loss, contamination, and the need for highly specialized operators. We report a system modularity chip for the analysis of rare targets (SMART-Chip) composed of three task-specific modules that can fully automate processing of CTCs. The modules were used for affinity selection of the CTCs from peripheral blood with subsequent photorelease, simultaneous counting, and viability determinations of the CTCs and staining/imaging of the CTCs for immunophenotyping. The modules were interconnected to a fluidic motherboard populated with valves, interconnects, pneumatic control channels, and a fluidic network. The SMART-Chip components were made from thermoplastics via microreplication, which lowers the cost of production making it amenable to clinical implementation. The utility of the SMART-Chip was demonstrated by processing blood samples secured from colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) patients. We were able to affinity-select EpCAM expressing CTCs with high purity (0-3 white blood cells/mL of blood), enumerate the selected cells, determine their viability, and immunophenotype the cells. The assay could be completed in <4 h, while manual processing required >8 h.