Nanotechnology-Assisted Isolation and Analysis of Circulating Tumor Cells on Microfluidic Devices

Cheng, Jie; Yang, Linjun; Zhao, Yang; Zhang, Lina; Zhang, Lingqian; Mao, Haiyang; Huang, Chengjun

doi:10.3390/mi11080774

Cited by 40 publications

(27 citation statements)

References 134 publications

(258 reference statements)

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“…Another example of CTC enrichment technology based on physical properties is the Parsortix ™ system that traps cells based on both deformability and size in disposable cassettes with channels that gradually decreases in size to approximately <10mm (26). A combinatory strategy using a microfluidic platforms and a nanotechnology-assisted separation has been also developed for CTC isolation (27). Alternative methods using microfiltrationbased enrichment which isolate tumor cells by size include ISET ® (Rarecells Diagnostics) (17) and ScreenCell ® (28).…”

Section: Identification and Characterization Of Ctcsmentioning

confidence: 99%

Early Dissemination of Circulating Tumor Cells: Biological and Clinical Insights

et al. 2021

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Circulating tumor cells (CTCs) play a causal role in the development of metastasis, the major cause of cancer-associated mortality worldwide. In the past decade, the development of powerful cellular and molecular technologies has led to a better understanding of the molecular characteristics and timing of dissemination of CTCs during cancer progression. For instance, genotypic and phenotypic characterization of CTCs, at the single cell level, has shown that CTCs are heterogenous, disseminate early and could represent only a minor subpopulation of the primary tumor responsible for disease relapse. While the impact of molecular profiling of CTCs has not yet been translated to the clinic, CTC enumeration has been widely used as a prognostic biomarker to monitor treatment response and to predict disease relapse. However, previous studies have revealed a major challenge: the low abundance of CTCs in the bloodstream of patients with cancer, especially in early stage disease where the identification and characterization of subsequently “lethal” cells has potentially the greatest clinical relevance. The CTC field is rapidly evolving with development of new technologies to improve the sensitivity of CTC detection, enumeration, isolation, and molecular profiling. Here we examine the technical and analytical validity of CTC technologies, we summarize current data on the biology of CTCs that disseminate early and review CTC-based clinical applications.

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Section: Identification and Characterization Of Ctcsmentioning

confidence: 99%

Early Dissemination of Circulating Tumor Cells: Biological and Clinical Insights

et al. 2021

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“…This setup allows for sample compatibility with genotypic or phenotypic downstream analysis (Fig. 1a) which can be helpful for understanding cellular clinical significance 37 .…”

Section: Resultsmentioning

confidence: 99%

Label-free enrichment of rare unconventional circulating neoplastic cells using a microfluidic dielectrophoretic sorting device

et al. 2021

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Cellular circulating biomarkers from the primary tumor such as circulating tumor cells (CTCs) and circulating hybrid cells (CHCs) have been described to harbor tumor-like phenotype and genotype. CHCs are present in higher numbers than CTCs supporting their translational potential. Methods for isolation of CHCs do not exist and are restricted to low-throughput, time consuming, and biased methodologies. We report the development of a label-free dielectrophoretic microfluidic platform facilitating enrichment of CHCs in a high-throughput and rapid fashion by depleting healthy peripheral blood mononuclear cells (PBMCs). We demonstrated up to 96.5% depletion of PBMCs resulting in 18.6-fold enrichment of cancer cells. In PBMCs from pancreatic adenocarcinoma patients, the platform enriched neoplastic cells identified by their KRAS mutant status using droplet digital PCR with one hour of processing. Enrichment was achieved in 75% of the clinical samples analyzed, establishing this approach as a promising way to non-invasively analyze tumor cells from patients.

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“…This setup allows for sample compatibility with genotypic or phenotypic downstream analysis (Fig. 1A) which can be helpful for understanding cellular clinical signi cance [38].…”

Section: Resultsmentioning

confidence: 99%

Label-free enrichment of rare unconventional circulating neoplastic cells using a microfluidic dielectrophoretic sorting device

Mira

Sapre

Walker

et al. 2021

Preprint

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Technologies that facilitate analyses of circulating biomarkers from blood for cancer detection are powerful tools for improving patient outcomes. Circulating biomarkers derived directly from the primary tumor have been identified including circulating tumor cells (CTCs) and circulating hybrid cells (CHCs), described to harbor phenotypes of both tumor cells and leukocytes. CHCs are present in higher numbers than CTCs which support their translational potential. Methods for isolation of CHCs do not exist and are restricted to low-throughput, time consuming, and biased methodologies. Here, we report development of a label-free dielectrophoretic (DEP) microfluidic platform facilitating enrichment of CHCs in a high-throughput and rapid fashion. Unlike other methods, depletion of healthy peripheral blood mononuclear cells (PBMCs) drives enrichment of CHCs. We analyzed DEP differential response of PBMCs and cancer cells and demonstrated up to 96.5% depletion of PBMCs resulting in 18.6-fold enrichment of cancer cells. In PBMCs from pancreatic adenocarcinoma patients, the platform enriched for neoplastic cells identified by their KRAS mutant status using droplet digital PCR from only 2 mL of whole blood with one hour of processing. Enrichment was achieved in 75% of the clinical samples analyzed, establishing this approach as a promising way to non-invasively analyze tumor cells from patients.

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Nanotechnology-Assisted Isolation and Analysis of Circulating Tumor Cells on Microfluidic Devices

Cited by 40 publications

References 134 publications

Early Dissemination of Circulating Tumor Cells: Biological and Clinical Insights

Early Dissemination of Circulating Tumor Cells: Biological and Clinical Insights

Label-free enrichment of rare unconventional circulating neoplastic cells using a microfluidic dielectrophoretic sorting device

Label-free enrichment of rare unconventional circulating neoplastic cells using a microfluidic dielectrophoretic sorting device

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