EpCAM-independent isolation of circulating tumor cells with epithelial-to-mesenchymal transition and cancer stem cell phenotypes using ApoStream® in patients with breast cancer treated with primary systemic therapy

Du, Fanny Le; Fujii, Takeo; Kida, Kumiko; Davis, Darren W.; Park, Minjeong; Liu, Diane D.; Wu, Weiguo; Chávez-MacGregor, Mariana; Barcenas, Carlos H.; Valero, Vicente; Tripathy, Debu; Reuben, James M.; Ueno, Naoto T.

doi:10.1371/journal.pone.0229903

Cited by 25 publications

(19 citation statements)

References 34 publications

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“…They reported that the recovery rate was over 70% and viability was more than 97%. Recently reported studies have verified the ability to isolate CTCs from clinical samples using the ApoStream™ system [222,223].…”

Section: Separation Of Cellsmentioning

confidence: 99%

A Prominent Cell Manipulation Technique in BioMEMS: Dielectrophoresis

2020

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BioMEMS, the biological and biomedical applications of micro-electro-mechanical systems (MEMS), has attracted considerable attention in recent years and has found widespread applications in disease detection, advanced diagnosis, therapy, drug delivery, implantable devices, and tissue engineering. One of the most essential and leading goals of the BioMEMS and biosensor technologies is to develop point-of-care (POC) testing systems to perform rapid prognostic or diagnostic tests at a patient site with high accuracy. Manipulation of particles in the analyte of interest is a vital task for POC and biosensor platforms. Dielectrophoresis (DEP), the induced movement of particles in a non-uniform electrical field due to polarization effects, is an accurate, fast, low-cost, and marker-free manipulation technique. It has been indicated as a promising method to characterize, isolate, transport, and trap various particles. The aim of this review is to provide fundamental theory and principles of DEP technique, to explain its importance for the BioMEMS and biosensor fields with detailed references to readers, and to identify and exemplify the application areas in biosensors and POC devices. Finally, the challenges faced in DEP-based systems and the future prospects are discussed.

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Section: Separation Of Cellsmentioning

confidence: 99%

A Prominent Cell Manipulation Technique in BioMEMS: Dielectrophoresis

2020

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“…This is advantageous as it is label free so separates cells independently of EpCAM expression and is highly specific, however expensive. The ApoStream technology (ApoCell) couples dielectrophoresis (DEP) with field-flow assist for the isolation of CTCs [ 126 ]. The device requires an initial Ficoll separation step to isolate PBMCs which are then processed using the device.…”

Section: Dielectrophoresismentioning

confidence: 99%

A Review of Circulating Tumour Cell Enrichment Technologies

Rushton

Nteliopoulos

Shaw

et al. 2021

Cancers

118

102

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Circulating tumour cells (CTCs) are the precursor cells for the formation of metastatic disease. With a simple blood draw, liquid biopsies enable the non-invasive sampling of CTCs from the blood, which have the potential to provide important insights into cancer detection and monitoring. Since gaining FDA approval in 2004, the CellSearch system has been used to determine the prognosis of patients with metastatic breast, prostate and colorectal cancers. This utilises the cell surface marker Epithelial Cell Adhesion Molecule (EpCAM), to enrich CTCs, and many other technologies have adopted this approach. More recently, the role of mesenchymal-like CTCs in metastasis formation has come to light. It has been suggested that these cells are more aggressive metastatic precursors than their epithelial counterparts; however, mesenchymal CTCs remain undetected by EpCAM-based enrichment methods. This has prompted the development of a variety of ‘label free’ enrichment technologies, which exploit the unique physical properties of CTCs (such as size and deformability) compared to other blood components. Here, we review a wide range of both immunocapture and label free CTC enrichment technologies, summarising the most significant advantages and disadvantages of each. We also highlight the important characteristics that technologies should possess for routine clinical use, since future developments could have important clinical implications, with the potential to direct personalised therapies for patients with cancer.

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“…DEP is an epCAM independent, label-free enrichment system, separating rare cells simply on the basis of their specific electrical properties [ 13 ]. The technique is capable of isolating all types of solid tumour-related immortalized cells from the NCI-60 panel [ 24 ], and more recently to co-collect, together with CTCs, also stem-like cells (CSCs) and mesenchymal-like cells (EMT-CTCs) [ 50 ].…”

Section: The Role Of Dep For Ctc Detection In Prostate Cancermentioning

confidence: 99%

“…The most advanced DACS system, Apostream™ (Precision Medicine Group, LLC), is based on a complex continuous field-flow DEP fractionation schema (FFF-DEP) [ 51 ]. The system was successfully tested for different solid tumours to capture epithelial-like CTCs as well as mesenchymal- and stem-like CTCs [ 50 , 51 ]. The main limit of ApoStream™, as for similar DEP-based sorting systems, is the use of planar, interdigitated electrode configurations causing exponentially decaying DEP forces, which limits the size of the sorting volume on which the DEP forces can act efficiently and reduces cell throughput.…”

Section: The Role Of Dep For Ctc Detection In Prostate Cancermentioning

confidence: 99%

The Role of Dielectrophoresis for Cancer Diagnosis and Prognosis

Russo

Musso

Romano

et al. 2021

Cancers

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Liquid biopsy is emerging as a potential diagnostic tool for prostate cancer (PC) prognosis and diagnosis. Unfortunately, most circulating tumor cells (CTC) technologies, such as AdnaTest or Cellsearch®, critically rely on the epithelial cell adhesion molecule (EpCAM) marker, limiting the possibility of detecting cancer stem-like cells (CSCs) and mesenchymal-like cells (EMT-CTCs) that are present during PC progression. In this context, dielectrophoresis (DEP) is an epCAM independent, label-free enrichment system that separates rare cells simply on the basis of their specific electrical properties. As compared to other technologies, DEP may represent a superior technique in terms of running costs, cell yield and specificity. However, because of its higher complexity, it still requires further technical as well as clinical development. DEP can be improved by the use of microfluid, nanostructured materials and fluoro-imaging to increase its potential applications. In the context of cancer, the usefulness of DEP lies in its capacity to detect CTCs in the bloodstream in their epithelial, mesenchymal, or epithelial–mesenchymal phenotype forms, which should be taken into account when choosing CTC enrichment and analysis methods for PC prognosis and diagnosis.

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EpCAM-independent isolation of circulating tumor cells with epithelial-to-mesenchymal transition and cancer stem cell phenotypes using ApoStream® in patients with breast cancer treated with primary systemic therapy

Cited by 25 publications

References 34 publications

A Prominent Cell Manipulation Technique in BioMEMS: Dielectrophoresis

A Prominent Cell Manipulation Technique in BioMEMS: Dielectrophoresis

A Review of Circulating Tumour Cell Enrichment Technologies

The Role of Dielectrophoresis for Cancer Diagnosis and Prognosis

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