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      DEPArray™ system: An automatic image‐based sorter for isolation of pure circulating tumor cells

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          Abstract

          Circulating tumor cells (CTCs) are rare cells shed into the bloodstream by invasive tumors and their analysis offers a promising noninvasive tool to predict and monitor therapeutic responses. CTCs can be isolated from patient blood and their characterization at single‐cell level can inform on the genomic landscape of a tumor. All CTC enrichment methods bear a burden of contaminating normal cells, which mandate a further step of purification to enable reliable downstream genetic analysis. Here, we describe the DEPArray™ technology, a microchip‐based digital sorter, which combines precise microfluidic and microelectronic enabling precise, image‐based isolation of single CTCs, which can then be analyzed by Next Generation Sequencing (NGS) methods. © 2018 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.

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          Circulating tumor cells: liquid biopsy of cancer.

          Catherine Alix-Panabières, Klaus Pantel (2013)
          The detection and molecular characterization of circulating tumor cells (CTCs) are one of the most active areas of translational cancer research, with >400 clinical studies having included CTCs as a biomarker. The aims of research on CTCs include (a) estimation of the risk for metastatic relapse or metastatic progression (prognostic information), (b) stratification and real-time monitoring of therapies, (c) identification of therapeutic targets and resistance mechanisms, and (d) understanding metastasis development in cancer patients. This review focuses on the technologies used for the enrichment and detection of CTCs. We outline and discuss the current technologies that are based on exploiting the physical and biological properties of CTCs. A number of innovative technologies to improve methods for CTC detection have recently been developed, including CTC microchips, filtration devices, quantitative reverse-transcription PCR assays, and automated microscopy systems. Molecular-characterization studies have indicated, however, that CTCs are very heterogeneous, a finding that underscores the need for multiplex approaches to capture all of the relevant CTC subsets. We therefore emphasize the current challenges of increasing the yield and detection of CTCs that have undergone an epithelial-mesenchymal transition. Increasing assay analytical sensitivity may lead, however, to a decrease in analytical specificity (e.g., through the detection of circulating normal epithelial cells). A considerable number of promising CTC-detection techniques have been developed in recent years. The analytical specificity and clinical utility of these methods must be demonstrated in large prospective multicenter studies to reach the high level of evidence required for their introduction into clinical practice. © 2012 American Association for Clinical Chemistry
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            Molecular analysis of circulating tumour cells-biology and biomarkers.

            Matthew G Krebs, Robert Metcalf, Louise Carter … (2014)
            Growing evidence for intratumour heterogeneity informs us that single-site biopsies fall short of revealing the complete genomic landscape of a tumour. With an expanding repertoire of targeted agents entering the clinic, screening tumours for genomic aberrations is increasingly important, as is interrogating the tumours for resistance mechanisms upon disease progression. Multiple biopsies separated spatially and temporally are impractical, uncomfortable for the patient and not without risk. Here, we describe how circulating tumour cells (CTCs), captured from a minimally invasive blood test-and readily amenable to serial sampling-have the potential to inform intratumour heterogeneity and tumour evolution, although it remains to be determined how useful this will be in the clinic. Technologies for detecting and isolating CTCs include the validated CellSearch(®) system, but other technologies are gaining prominence. We also discuss how recent CTC discoveries map to mechanisms of haematological spread, previously described in preclinical models, including evidence for epithelial-mesenchymal transition, collective cell migration and cells with tumour-initiating capacity within the circulation. Advances in single-cell molecular analysis are enhancing our ability to explore mechanisms of metastasis, and the combination of CTC and cell-free DNA assays are anticipated to provide invaluable blood-borne biomarkers for real-time patient monitoring and treatment stratification.
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              Circulating tumor cell technologies.

              Klaus Pantel, Catherine Alix-Panabières, Meghaan M Ferreira … (2016)
              Circulating tumor cells, a component of the "liquid biopsy", hold great potential to transform the current landscape of cancer therapy. A key challenge to unlocking the clinical utility of CTCs lies in the ability to detect and isolate these rare cells using methods amenable to downstream characterization and other applications. In this review, we will provide an overview of current technologies used to detect and capture CTCs with brief insights into the workings of individual technologies. We focus on the strategies employed by different platforms and discuss the advantages of each. As our understanding of CTC biology matures, CTC technologies will need to evolve, and we discuss some of the present challenges facing the field in light of recent data encompassing epithelial-to-mesenchymal transition, tumor-initiating cells, and CTC clusters.
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                Author and article information

                Contributors
                Gianni Medoro: gmedoro@siliconbiosystems.com
                Journal
                Journal ID (nlm-ta): Cytometry A
                Journal ID (iso-abbrev): Cytometry A
                Journal ID (doi): 10.1002/(ISSN)1552-4930
                Journal ID (publisher-id): CYTO
                Title: Cytometry
                Publisher: John Wiley & Sons, Inc. (Hoboken, USA )
                ISSN (Print): 1552-4922
                ISSN (Electronic): 1552-4930
                Publication date (Electronic): 14 December 2018
                Publication date (Print): December 2018
                Volume: 93
                Issue: 12 , Circulating Tumor Cells ( doiID: 10.1002/cyto.a.v93.12 )
                Pages: 1260-1266
                Affiliations
                [ 1 ] Menarini Silicon Biosystems S.p.A Bologna Italy
                Author notes
                [*] [* ]Correspondence to: Gianni Medoro, Menarini Silicon Biosystems S.p.A., Via Giuseppe Di Vittorio 21/B3, I‐40013 Castel Maggiore (BO), Italy. Email: gmedoro@ 123456siliconbiosystems.com
                Article
                Publisher ID: CYTOA23687
                DOI: 10.1002/cyto.a.23687
                PMC ID: 6590341
                PubMed ID: 30551261
                SO-VID: c451ca18-5578-481b-a6fc-bfe051d5caae
                Copyright © © 2018 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                Date received : 11 October 2018
                Date revision received : 02 November 2018
                Date accepted : 05 November 2018
                Page count
                Figures: 3, Tables: 0, Pages: 7, Words: 4862
                Funding
                Funded by: Electronic Components and Systems for European Leadership (ECSEL)
                Award ID: 661796
                Categories
                Subject: Review Article
                Subject: Review Article
                Custom metadata
                source-schema-version-number 2.0
                component-id cytoa23687
                cover-date December 2018
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.4 mode:remove_FC converted:24.06.2019

                ScienceOpen disciplines: Cell biology
                Keywords: circulating tumor cells,cancer cells,image‐based sorting,pure cells,single cells,liquid biopsy,rare cells
                Data availability:
                ScienceOpen disciplines: Cell biology
                Keywords: circulating tumor cells, cancer cells, image‐based sorting, pure cells, single cells, liquid biopsy, rare cells

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