A herringbone mixer based microfluidic device HBEXO-chip for purifying tumor-derived exosomes and establishing miRNA signature in pancreatic cancer

Zhang, Yong; Tong, Xuedong; Yang, Liu; Yin, Ruiling; Li, Yan; Zeng, Dong; Wang, Xiaoyao; Deng, Kun

doi:10.1016/j.snb.2021.129511

Cited by 38 publications

(31 citation statements)

References 35 publications

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“…A high throughput implementation of immunoaffinity separation is the HB EXO-Chip, a device featuring eight channels and a herringbone design that allows for the separation of EVs 30-150 nm in diameter from plasma [90]. The capture efficiency was calculated by allowing 50 million exosomes per milliliter of PBS solution to flow into the device, followed by measuring the concentration of nanoparticles before and after the sample run through the HB EXO-Chip to determine the number of particles captured [90]. The HB EXO-Chip has demonstrated a 75% capture efficiency of tumor-derived exosomes from plasma [90].…”

Section: Isolation Based On Immunoaffinitymentioning

confidence: 99%

“…The capture efficiency was calculated by allowing 50 million exosomes per milliliter of PBS solution to flow into the device, followed by measuring the concentration of nanoparticles before and after the sample run through the HB EXO-Chip to determine the number of particles captured [90]. The HB EXO-Chip has demonstrated a 75% capture efficiency of tumor-derived exosomes from plasma [90]. Other devices reported for isolating EVs 50-150 nm in diameter have targeted specific cancer biomarkers [91].…”

Section: Isolation Based On Immunoaffinitymentioning

confidence: 99%

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Microfluidic Approaches and Methods Enabling Extracellular Vesicle Isolation for Cancer Diagnostics

et al. 2022

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Advances in cancer research over the past half-century have clearly determined the molecular origins of the disease. Central to the use of molecular signatures for continued progress, including rapid, reliable, and early diagnosis is the use of biomarkers. Specifically, extracellular vesicles as biomarker cargo holders have generated significant interest. However, the isolation, purification, and subsequent analysis of these extracellular vesicles remain a challenge. Technological advances driven by microfluidics-enabled devices have made the challenges for isolation of extracellular vesicles an emerging area of research with significant possibilities for use in clinical settings enabling point-of-care diagnostics for cancer. In this article, we present a tutorial review of the existing microfluidic technologies for cancer diagnostics with a focus on extracellular vesicle isolation methods.

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Section: Isolation Based On Immunoaffinitymentioning

confidence: 99%

Section: Isolation Based On Immunoaffinitymentioning

confidence: 99%

Microfluidic Approaches and Methods Enabling Extracellular Vesicle Isolation for Cancer Diagnostics

et al. 2022

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“…Zhang et al developed a herringbone mixer-based microfluidic chip that was able to directly separate exosomes from plasma using an immunoaffinity-based approach. This method enabled the successful enrichment of pancreatic cancer expressing Glypican-1 exosome subpopulations with 75% efficiency [91]. Recently, another research group demonstrated the feasibility of a solid-phase, microprobe-based technology for CD63-specific exosome purification that can further be integrated with a microfluidic platform for high-throughput and integrated omics analysis [42].…”

Section: Immunoaffinity Sensorsmentioning

confidence: 99%

“…Zhang et al developed a herringbone mixerbased microfluidic chip that was able to directly separate exosomes from plasma using an immunoaffinity-based approach. This method enabled the successful enrichment of pancreatic cancer expressing Glypican-1 exosome subpopulations with 75% efficiency [91].…”

Section: Immunoaffinity Sensorsmentioning

confidence: 99%

Advances in Biosensors Technology for Detection and Characterization of Extracellular Vesicles

Bari

Hossain

Nestorova

2021

Sensors

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Exosomes are extracellular vehicles (EVs) that encapsulate genomic and proteomic material from the cell of origin that can be used as biomarkers for non-invasive disease diagnostics in point of care settings. The efficient and accurate detection, quantification, and molecular profiling of exosomes are crucial for the accurate identification of disease biomarkers. Conventional isolation methods, while well-established, provide the co-purification of proteins and other types of EVs. Exosome purification, characterization, and OMICS analysis are performed separately, which increases the complexity, duration, and cost of the process. Due to these constraints, the point-of-care and personalized analysis of exosomes are limited in clinical settings. Lab-on-a-chip biosensing has enabled the integration of isolation and characterization processes in a single platform. The presented review discusses recent advancements in biosensing technology for the separation and detection of exosomes. Fluorescent, colorimetric, electrochemical, magnetic, and surface plasmon resonance technologies have been developed for the quantification of exosomes in biological fluids. Size-exclusion filtration, immunoaffinity, electroactive, and acoustic-fluid-based technologies were successfully applied for the on-chip isolation of exosomes. The advancement of biosensing technology for the detection of exosomes provides better sensitivity and a reduced signal-to-noise ratio. The key challenge for the integration of clinical settings remains the lack of capabilities for on-chip genomic and proteomic analysis.

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“…10 min after bonding, microfluidic channels (n = 3 of each design) were functionalised with an antibody against CD63 (SantaCruz, sc-5275) by using a well-established linker chemistry 4,[28][29][30] . Briefly, 8% percent (3-Aminopropyl)triethoxysilane (APTES, Sigma) in ethanol was flowed at a rate of 20 µl/min for 15 min then left stagnant for 20 min, followed by a flush with pure ethanol.…”

Section: Ev Capture Efficiency Quantificationmentioning

confidence: 99%

Automated Parallel Pattern Search Optimisation of Microfluidic Geometry for Extracellular Vesicle Liquid Biopsies

Hisey

Lim²,

Tyler³

et al. 2021

Preprint

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Microfluidic liquid biopsies using affinity-based capture of extracellular vesicles (EVs) have demonstrated great potential for providing rapid disease diagnosis and monitoring. However, little effort has been devoted to optimising the geometry of the microfluidic channels for maximum EV capture due to the inherent challenges of physically testing many geometric designs. To address this, we developed an automated parallel pattern search (PPS) optimiser by combining a Python optimiser, COMSOL Multiphysics, and high performance computing. This unique approach was applied to a triangular micropillar array geometry by parameterising repeating unit cells, making several assumptions, and optimising for maximum particle capture efficiency. We successfully optimised the triangular pillar arrays and surprisingly found that simply maximising the total number of pillars and effective surface area did not result in maximum EV capture, as devices with slightly larger pillars and more spacing between pillars allowed contact with slower moving EVs that followed the pillar contours more closely. We then experimentally validated this finding using bioreactor-produced EVs in the best and worst channel designs that were functionalised with an antibody against CD63. Captured EVs were quantified using a fluorescent plate reader, followed by an established elution method and nanoparticle tracking analysis. These results demonstrate the power of automated microfluidic geometry optimisations for EV liquid biopsies and will support further development of this rapidly growing field.

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A herringbone mixer based microfluidic device HBEXO-chip for purifying tumor-derived exosomes and establishing miRNA signature in pancreatic cancer

Cited by 38 publications

References 35 publications

Microfluidic Approaches and Methods Enabling Extracellular Vesicle Isolation for Cancer Diagnostics

Microfluidic Approaches and Methods Enabling Extracellular Vesicle Isolation for Cancer Diagnostics

Advances in Biosensors Technology for Detection and Characterization of Extracellular Vesicles

Automated Parallel Pattern Search Optimisation of Microfluidic Geometry for Extracellular Vesicle Liquid Biopsies

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