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Review
. 2019 Jul 23;13(4):041503.
doi: 10.1063/1.5087690. eCollection 2019 Jul.

Recent advances in microfluidic methods in cancer liquid biopsy

Florina S Iliescu  1 , Daniel P Poenar  2 , Fang Yu  3 , Ming Ni  4 , Kiat Hwa Chan  5 , Irina Cima  6 , Hayden K Taylor  7 , Igor Cima  8 , Ciprian Iliescu
Affiliations
Review

Recent advances in microfluidic methods in cancer liquid biopsy

Florina S Iliescu et al. Biomicrofluidics. .

Abstract

Early cancer detection, its monitoring, and therapeutical prediction are highly valuable, though extremely challenging targets in oncology. Significant progress has been made recently, resulting in a group of devices and techniques that are now capable of successfully detecting, interpreting, and monitoring cancer biomarkers in body fluids. Precise information about malignancies can be obtained from liquid biopsies by isolating and analyzing circulating tumor cells (CTCs) or nucleic acids, tumor-derived vesicles or proteins, and metabolites. The current work provides a general overview of the latest on-chip technological developments for cancer liquid biopsy. Current challenges for their translation and their application in various clinical settings are discussed. Microfluidic solutions for each set of biomarkers are compared, and a global overview of the major trends and ongoing research challenges is given. A detailed analysis of the microfluidic isolation of CTCs with recent efforts that aimed at increasing purity and capture efficiency is provided as well. Although CTCs have been the focus of a vast microfluidic research effort as the key element for obtaining relevant information, important clinical insights can also be achieved from alternative biomarkers, such as classical protein biomarkers, exosomes, or circulating-free nucleic acids. Finally, while most work has been devoted to the analysis of blood-based biomarkers, we highlight the less explored potential of urine as an ideal source of molecular cancer biomarkers for point-of-care lab-on-chip devices.

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Figures

FIG. 1.
FIG. 1.
Distribution of size of hematopoietic cells and comparison with the size range of CTCs. The overlap in size between WBCs and CTCs is also highlighted.
FIG. 2.
FIG. 2.
Schematic representations of various types of CTC isolation microdevices reported in the literature: (a) Label-free CTCs isolation from a blood sample using inertial microfluidics. Reproduced with permission from Warkiani et al., Nat. Protoc. 11(1), 134 (2016). Copyright 2016 Nature Publishing Group. (b) SEM photo of the micropillars in the device of Nagrath et al. with a captured NCI-H1650 lung cancer cell. Reproduced with permission from Nagrath et al., Nature 450(7173), 1235 (2007). Copyright 2007 Nature Publishing Group. (c) The VerIFAST device for cell isolation, cellular staining, and downstream analysis. Reproduced with permission from Casavant et al., Lab Chip 13(3), 391–396 (2013). Copyright 2013 The Royal Society of Chemistry. (d) Schematic illustrations of how the CTCs captured in the NanoVELCRO device may also be released for subsequent processing, respectively. Reproduced with permission from Wang et al., Angew. Chem. 123(13), 3140–3144 (2011). Copyright 2011 John Wiley and Sons.
FIG. 3.
FIG. 3.
Different LOC solutions that combine two or more methods for efficient CTCs isolation: (a) Schematic of the concentrator mechanism and of the ratchet cell sorter (Lin et al.). Reproduced with permission from Lin et al., Biomicrofluidics 7(3), 034114 (2013). Copyright 2013 AIP Publishing LLC. (b) A Multi-Obstacle Architecture (MOA) for filtration of CTCs. Reproduced with permission from Kim et al., Lab Chip 12(16), 2874–2880 (2012). Copyright 2012 The Royal Society of Chemistry. (c) Cross-sectional view of the microaperture chip system of Chang et al. (CTCs immunomagnetic isolation together with subsequent size-based filtration). Reproduced with permission from Chang et al., IEEE Sensors J. 14(9), 3008–3013 (2014). Copyright 2014 IEEE. (d) Cross-sectional image and 3D representation of the geometrically activated surface interaction (GASI) chip for negative enrichment of CTCs. The asymmetric herringbone structure creates a helical fluid flow that enhances significantly the interaction between the cells and the antibody-coated channel surface. Depletion of WBCs can be achieved by functionalizing the chip surfaces with CD45 antibodies, thus allowing CTCs to flow freely to the outlet. Reproduced with permission from Hyun et al., Anal. Chem. 85(9), 4439–4445 (2013). Copyright 2013 American Chemical Society.
FIG. 4.
FIG. 4.
Microfluidic approaches for cfNA isolation: (a) The sensor-based clamp-chip for electrochemical analysis of cfNA mutations developed by Das et al. The microsensor is modified by a PNA probe and only targets mutant nucleic acids. Nontarget mutants and wild-type sequences are washed away. Electrochemical readout is generated by an electrocatalytic reporter system. cfNA hybridization is observed by differential pulse voltammetry signal changes. Reproduced with permission from Das et al., Nat. Chem. 7(7), 569 (2015). Copyright 2015 Nature Publishing Group. (b) On-chip surface acoustic wave lysis and ion-exchange nanomembrane detection of exosomal RNA for pancreatic cancer study and diagnosis developed by Taller et al. Reproduced with permission from Taller et al., Lab Chip 15(7), 1656–1666 (2015). Copyright 2015 The Royal Society of Chemistry.
FIG. 5.
FIG. 5.
Different LOC solutions for exosome isolation: (a) The ExoChip (top) and its operation procedure (bottom) used for exosomes isolation and analysis. Reproduced with permission from Kanwar et al., Lab Chip 14(11), 1891–1900 (2014). Copyright 2014 The Royal Society of Chemistry. (b) ExoSearch: a robust, continuous-flow design provides enriched preparation of blood plasma exosomes for in situ, multiplexed detection using immunomagnetic beads for quantitative isolation and release of blood plasma exosomes in a wide range of preparation volumes. Reproduced with permission from Zhao et al., Lab Chip 16(3), 489–496 (2016). Copyright 2016 The Royal Society of Chemistry. (c) Nano-IMEX: (A) Schematic of a single-channel PDMS/glass device, with the exploded-view highlighting the coated PDMS chip containing an array of Y-shaped microposts. (B) Surface of the channel and microposts coated with graphene oxide and polydopamine as a nanostructured interface for the sandwich ELISA of exosomes with enzymatic fluorescence signal amplification. Reproduced with permission from Zhang et al., Lab Chip 16(16), 3033–3042 (2016). Copyright 2016 The Royal Society of Chemistry.
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References

    1. World Health Organization, International Agency for Research on Cancer (2018).
    1. Crowley E., Di Nicolantonio F., Loupakis F., and Bardelli A., Nat. Rev. Clin. Oncol. 10(8), 472 (2013). 10.1038/nrclinonc.2013.110 - DOI - PubMed
    1. Vaidyanathan R., Soon R. H., Zhang P., Jiang K., and Lim C. T., Lab Chip 19(1), 11–34 (2019). 10.1039/C8LC00684A - DOI - PubMed
    1. Krebs M. G., Metcalf R. L., Carter L., Brady G., Blackhall F. H., and Dive C., Nat. Rev. Clin. Oncol. 11(3), 129–144 (2014). 10.1038/nrclinonc.2013.253 - DOI - PubMed
    1. Ilié M. and Hofman P., Trans. Lung Cancer Res. 5(4), 420 (2016). 10.21037/tlcr.2016.08.06 - DOI - PMC - PubMed

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