Continuous centrifugal microfluidics (CCM) isolates heterogeneous circulating tumor cells via full automation

Abstract

Understanding cancer heterogeneity is essential to finding diverse genetic mutations in metastatic cancers. Thus, it is critical to isolate all types of CTCs to identify accurate cancer information from patients. Moreover, full automation robustly capturing the full spectrum of CTCs is an urgent need for CTC diagnosis to be routine clinical practice. Methods: Here we report the full capture of heterogeneous CTC populations using fully automated, negative depletion-based continuous centrifugal microfluidics (CCM). Results: The CCM system demonstrated high performance (recovery rates exceeding 90% and WBC depletion rate of 99.9%) across a wide range of phenotypes (EpCAM(+), EpCAM(-), small-, large-sized, and cluster) and cancers (lung, breast, and bladder). Applied in 30 lung adenocarcinoma patients harboring epidermal growth factor receptor (EGFR) mutations, the system isolated diverse phenotypes of CTCs in marker expression and size, implying the importance of unbiased isolation. Genetic analyses of intra-patient samples comparing cell-free DNA with CCM-isolated CTCs yielded perfect concordance, and CTC enumeration using our technique was correlated with clinical progression as well as response to EGFR inhibitors. Conclusion: Our system also introduces technical advances which assure rapid, reliable, and reproducible results, thus enabling a more comprehensive application of robust CTC analysis in clinical practice.

Lossless Immunocytochemistry Based on Large-Scale Porous Hydrogel Pellicle for Accurate Rare Cell Analysis

“…2020-10-033). CTCs and circulating fetal cells were isolated in a similar manner to the previous method …”

“…CTCs and circulating fetal cells were isolated in a similar manner to the previous method. 20 Fabrication of HypICC Platform. Owing to its biocompatibility and high optical transmittance, polydimethylsiloxane (PDMS) is suitable for visually monitoring biological cells.…”

Recent progress of nanostructure-based enrichment of circulating tumor cells and downstream analysis

“…The recovery rate is more than 90% and the depletion rate is 99.9%. 39 In addition, the detection and analysis of blood samples from 30 patients with non-small cell lung cancer showed that there was a good correlation between the EGFR mutation spectrum of CTCs and the spectrum of circulating tumor DNA (CtDNA). In patients with insufficient ctDNA for mutation analysis, CTC analysis may be an auxiliary decision-making tool.…”

Fully Automated Continuous Centrifugal Microfluidics Isolates Natural Killer Cells with High Performance and Minimal Stress

“…In this study, we introduce a fully automated continuous centrifugal microfluidics-based NK disc (CCM-NKD) for NK cell isolation. The centrifugal microfluidic system has been investigated and applied in various fields, including the isolation of rare cells such as CTCs , and trophoblasts, as well as primary neuron cell isolation and nucleic acid testing . The CCM-NKD implements a negative selection strategy, eliminating non-NK cells to increase the NK cell concentration.…”