Ultra-fast, label-free isolation of circulating tumor cells from blood using spiral microfluidics

Warkiani, Majid Ebrahimi; Khoo, Bee Luan; Wu, Lidan; Tay, Andy; Bhagat, Ali Asgar S.; Han, Jongyoon; Lim, Chwee Teck

doi:10.1038/nprot.2016.003

Cited by 486 publications

(437 citation statements)

References 74 publications

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“…Aya-Bonilla and colleagues [4] more recently interrogated for the first time, the enrichment of MelCTCs using spiral microfluidic technology [59,60]. With this device, recovery rates of greater than 55% and a 2.5e3 log depletion of WBCs were observed in spiking experiments using melanoma cell lines with different cell sizes which represents an improvement to depletion rates similar to those obtained by the CTC-iChip [41].…”

Section: Melanoma Ctc Detection Methodsmentioning

confidence: 76%

Melanoma circulating tumor cells: Benefits and challenges required for clinical application

et al. 2018

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a b s t r a c tThe implementation of novel therapeutic interventions has improved the survival rates of melanoma patients with metastatic disease. Nonetheless, only 33% of treated cases exhibit long term responses. Circulating tumor cell (CTC) measurements are currently of clinical value in breast, prostate and colorectal cancers. However, the clinical utility of melanoma CTCs (MelCTCs) is still unclear due to challenges that appear intrinsic to MelCTCs (i.e. rarity, heterogeneity) and a lack of standardization in their isolation, across research laboratories. Here, we review the latest developments, pinpoint the challenges in MelCTC isolation and address their potential role in melanoma management.

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Section: Melanoma Ctc Detection Methodsmentioning

confidence: 76%

Melanoma circulating tumor cells: Benefits and challenges required for clinical application

et al. 2018

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“…Detection was achieved in 20 out of 20 (Hou et al, 2013) and 10 out of 10 samples . A detailed protocol of Warkiani's device was published recently (Warkiani et al, 2016) showing a multiplexed version that increased the device recovery efficiency to 85% while retaining its high throughput (Warkiani et al, 2014).…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Skeletal stem cell isolation: A review on the state-of-the-art microfluidic label-free sorting techniques

Martín

Oreffo

Morgan

2016

Biotechnology Advances

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Skeletal stem cells (SSC) are a sub-population of bone marrow stromal cells that reside in postnatal bone marrow with osteogenic, chondrogenic and adipogenic differentiation potential. SSCs reside only in the bone marrow and have organisational and regulatory functions in the bone marrow microenvironment and give rise to the haematopoiesis-supportive stroma. Their differentiation capacity is restricted to skeletal lineages and therefore the term SSC should be clearly distinguished from mesenchymal stem cells which are reported to exist in extra-skeletal tissues and, critically, do not contribute to skeletal development.SSCs are responsible for the unique regeneration capacity of bone and offer unlimited potential for application in bone regenerative therapies. A current unmet challenge is the isolation of homogeneous populations of SSCs, in vitro, with homogeneous regeneration and differentiation capacities. Challenges that limit SSC isolation include a) the scarcity of SSCs in bone marrow aspirates, estimated at between 1 in 10-100,000 mononuclear cells; b) the absence of specific markers and thus the phenotypic ambiguity of the SSC and c) the complexity of bone marrow tissue.Microfluidics provides innovative approaches for cell separation based on bio-physical features of single cells. Here we review the physical principles underlying label-free microfluidic sorting techniques and review their capacity for stem cell selection/sorting from complex (heterogeneous) samples.

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“…Several physical differences between CTCs and leukocytes can be exploited. Size-based filtration harnesses the fact that CTCs tend to be larger than leukocytes [72][73][74]. CTCs typically have higher membrane capacitance than leuko cytes, in large part because of greater total surface area, allowing for their isolation by dielectrophoresis field-flow fractionation [75].…”

Section: Physical Separationmentioning

confidence: 99%

The Promise of Circulating Tumor Cells for Precision Cancer Therapy

Hwang

Miyamoto

2016

Biomark. Med.

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The rapidly growing array of therapeutic options in cancer requires informative biomarkers to guide the rational selection and precision application of appropriate therapies. Circulating biomarkers such as circulating tumor cells have immense potential as noninvasive, serial 'liquid biopsies' that may be more representative of the complete spectrum of a patient's individual malignancy than spatially and temporally restricted tumor biopsies. In this review, we discuss the current state-of-the-art in the isolation and molecular characterization of circulating tumor cells as well as their utility in a wide range of clinical applications such as prognostics, treatment monitoring and identification of novel therapeutic targets and resistance mechanisms to enable real-time adjustments in the clinical management of cancer. The evolving landscape of cancer therapy creates an urgent need for minimally invasive biomarkers to facilitate early detection, prognosis and prediction of therapeutic response and resistance to enable highly adaptable, real-time precision therapy [1]. The conventional gold standard of using single biopsies of the primary tumor to inform all downstream therapeutic decisions may no longer be adequate given increasing evidence of significant spatial and temporal hetero geneity in tumors [2], especially when placed under the selection pressure of various treatments. Moreover, serial biopsies are often impractical, morbid and technically challenging.In this review, we focus on the emerging role of circulating tumor cells (CTCs), which can be serially obtained from minimally invasive blood draws or 'liquid biopsies'. CTCs are cancer cells that have been shed into the peripheral circulation from primary or metastatic tumors [3,4]. The first reported observation of CTCs was in 1869 by Australian pathologist Thomas Ashworth at the autopsy of a patient with metastatic cancer [5]. By comparing the morphology of circulating cells with those from different cancerous lesions, Ashworth came to the prescient conclusion that 'cells identical with those of the cancer itself being seen in the blood may tend to throw some light upon the mode of origin of multiple tumors existing in the same person' [5]. Indeed, molecular analyses of CTCs may be superior to individual tumor biopsies because these circulating cells likely provide a sampling of different regions of the primary tumor as well as metastatic deposits, and therefore are more likely to capture the genetic heterogeneity of a patient's cancer.While cell-free circulating tumor DNA (ctDNA) is an important, complementary biomarker to CTCs, it has been reviewed extensively elsewhere and will not be discussed in this review [4,6]. Moreover, although ctDNA may in some cases be more reliably [7], they are largely limited to genomic mutational analysis. In contrast, CTC analysis can provide a wealth of other information including cell morphology, immunocytochemical phenotype, presence of important epitopes, presence of multiple mutations within a single cell to decode ...

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Ultra-fast, label-free isolation of circulating tumor cells from blood using spiral microfluidics

Cited by 486 publications

References 74 publications

Melanoma circulating tumor cells: Benefits and challenges required for clinical application

Melanoma circulating tumor cells: Benefits and challenges required for clinical application

Skeletal stem cell isolation: A review on the state-of-the-art microfluidic label-free sorting techniques

The Promise of Circulating Tumor Cells for Precision Cancer Therapy

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