scholarly journals Functional profiling of circulating tumor cells with an integrated vortex capture and single-cell protease activity assay

2018 ◽  
Vol 115 (40) ◽  
pp. 9986-9991 ◽  
Author(s):  
Manjima Dhar ◽  
Jeffrey Nam Lam ◽  
Tonya Walser ◽  
Steven M. Dubinett ◽  
Matthew B. Rettig ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Activity Ratio ◽  
Proteolytic Enzymes ◽  
Microfluidic System ◽  
Matrix Metalloprotease ◽  
Rare Cancer ◽  
Companion Diagnostics ◽  
Functional Profiling ◽  
Vortex Capture

Tumor cells are hypothesized to use proteolytic enzymes to facilitate invasion. Whether circulating tumor cells (CTCs) secrete these enzymes to aid metastasis is unknown. A quantitative and high-throughput approach to assay CTC secretion is needed to address this question. We developed an integrated microfluidic system that concentrates rare cancer cells >100,000-fold from 1 mL of whole blood into ∼50,000 2-nL drops composed of assay reagents within 15 min. The system isolates CTCs by size, exchanges fluid around CTCs to remove contaminants, introduces a matrix metalloprotease (MMP) substrate, and encapsulates CTCs into microdroplets. We found CTCs from prostate cancer patients possessed above baseline levels of MMP activity (1.7- to 200-fold). Activity of CTCs was generally higher than leukocytes from the same patient (average CTC/leukocyte MMP activity ratio, 2.6 ± 1.5). Higher MMP activity of CTCs suggests active proteolytic processes that may facilitate invasion or immune evasion and be relevant phenotypic biomarkers enabling companion diagnostics for anti-MMP therapies.

A Microfluidic Platform for On-Chip Analysis of Circulating Tumor Cells

2021 ◽  
Author(s):  
Jeff Darabi ◽  
Joseph Schober
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Whole Blood ◽  
Peripheral Blood ◽  
Automated Image Analysis ◽  
Rare Cancer ◽  
On Chip ◽  
Chip Analysis ◽  
Selection Of

Abstract Studies have shown that primary tumor sites begin shedding cancerous cells into peripheral blood at early stages of cancer, and the presence and frequency of circulating tumor cells (CTCs) in blood is directly proportional to disease progression. The challenge is that the concentration of the CTCs in peripheral blood may be extremely low. In the past few years, several microfluidic-based concepts have been investigated to isolate CTCs from whole blood. However, these devices are generally hampered by complex fabrication processes and very low volumetric throughputs, which may not be practical for rapid clinical applications. This paper presents a high-performance yet simple magnetophoretic microfluidic chip for the enrichment and on-chip analysis of rare CTCs from blood. Microscopic and flow cytometric assays developed for selection of cancer cell lines, selection of monoclonal antibodies, and optimization of bead coupling are discussed. Additionally, on-chip characterization of rare cancer cells using high resolution immunofluorescence microscopy and modeling results for prediction of CTC capture length are presented. The device has the ability to interface directly with on-chip pre and post processing modules such as mixing, incubation, and automated image analysis systems. These features will enable us to isolate rare cancer cells from whole blood and detect them on the chip with subcellular resolution.

scholarly journals Integrative Analysis and Machine Learning based Characterization of Single Circulating Tumor Cells

2020 ◽  
Vol 9 (4) ◽  
pp. 1206 ◽  
Author(s):  
Arvind Iyer ◽  
Krishan Gupta ◽  
Shreya Sharma ◽  
Kishore Hari ◽  
Yi Fang Lee ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Expression Profiles ◽  
Gene Expression Pattern ◽  
Microfluidic System ◽  
Integrative Analysis ◽  
Label Free ◽  
Peripheral Blood Mononuclear ◽  
Cell Expression

We collated publicly available single-cell expression profiles of circulating tumor cells (CTCs) and showed that CTCs across cancers lie on a near-perfect continuum of epithelial to mesenchymal (EMT) transition. Integrative analysis of CTC transcriptomes also highlighted the inverse gene expression pattern between PD-L1 and MHC, which is implicated in cancer immunotherapy. We used the CTCs expression profiles in tandem with publicly available peripheral blood mononuclear cell (PBMC) transcriptomes to train a classifier that accurately recognizes CTCs of diverse phenotype. Further, we used this classifier to validate circulating breast tumor cells captured using a newly developed microfluidic system for label-free enrichment of CTCs.

ClearCell FX Microfluidic System for the Enrichment and Genetic Analysis of Circulating Tumor Cells.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e22023-e22023
Author(s):  
Sohan Lal Punia ◽  
LIntao Bi ◽  
Mehmet Akif Turker ◽  
Jin Sung Jang ◽  
Michael B Campion ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Microfluidic System

scholarly journals Dynamic Halbach array magnet integrated microfluidic system for the continuous-flow separation of rare tumor cells

RSC Advances ◽  
2019 ◽  
Vol 9 (66) ◽  
pp. 38496-38504 ◽  
Author(s):  
Mei Xue ◽  
An Xiang ◽  
Yanhai Guo ◽  
Li Wang ◽  
Rou Wang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Flow Separation ◽  
Whole Blood ◽  
Continuous Flow ◽  
Microfluidic System ◽  
Rare Tumor ◽  
Halbach Array

We develop a dynamic Halbach array magnet integrated microfluidic system for continuous-flow separation of circulating tumor cells from whole blood.

High throughput capture of circulating tumor cells using an integrated microfluidic system

2013 ◽  
Vol 47 ◽  
pp. 113-119 ◽  
Author(s):  
Zongbin Liu ◽  
Wang Zhang ◽  
Fei Huang ◽  
Hongtao Feng ◽  
Weiliang Shu ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
High Throughput ◽  
Microfluidic System
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