Glycan Stimulation Enables Purification of Prostate Cancer Circulating Tumor Cells on PEDOT NanoVelcro Chips for RNA Biomarker Detection

Shen, Mo-Yuan; Chen, Jie‐Fu; Luo, Chun-Hao; Lee, Sang-Jun; Li, Cheng‐Hsuan; Yang, Yung-Ling; Tsai, Yu-Han; Ho, Bo-Cheng; Bao, Lirong; Lee, Tien-Jung; Jan, Yu Jen; Zhu, Yazhen; Cheng, Shirley; Feng, Felix Y.; Chen, Peilin; Hou, Shuang; Agopian, Vatche G.; Hsiao, Yu-Sheng; Tseng, Hsian‐Rong; Posadas, Edwin M.; Yu, Hsiao‐hua

doi:10.1002/adhm.201700701

Cited by 43 publications

(46 citation statements)

References 74 publications

(45 reference statements)

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“…Several techniques are available for the recovery of cells intact from microfluidic devices [43–45, 49, 50]. Here, we employed an air foam approach—using a mixture of air and cell culture medium containing bovine serum albumin (BSA)—for the efficient release of the captured cancer cells from our microfluidic devices (Fig.…”

Section: Resultsmentioning

confidence: 99%

Random and aligned electrospun PLGA nanofibers embedded in microfluidic chips for cancer cell isolation and integration with air foam technology for cell release

Chen

Yeh

et al. 2019

J Nanobiotechnol

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Background Circulating tumor cells (CTCs) comprise the high metastatic potential population of cancer cells in the blood circulation of humans; they have become the established biomarkers for cancer diagnosis, individualized cancer therapy, and cancer development. Technologies for the isolation and recovery of CTCs can be powerful cancer diagnostic tools for liquid biopsies, allowing the identification of malignancies and guiding cancer treatments for precision medicine. Methods We have used an electrospinning process to prepare poly(lactic- co -glycolic acid) (PLGA) nanofibrous arrays in random or aligned orientations on glass slips. We then fabricated poly(methyl methacrylate) (PMMA)-based microfluidic chips embedding the PLGA nanofiber arrays and modified their surfaces through sequential coating with using biotin–(PEG) 7 –amine through EDC/NHS activation, streptavidin (SA), and biotinylated epithelial-cell adhesion-molecule antibody (biotin-anti-EpCAM) to achieve highly efficient CTC capture. When combined with an air foam technology that induced a high shear stress and, thereby, nondestructive release of the captured cells from the PLGA surfaces, the proposed device system operated with a high cell recovery rate. Results The morphologies and average diameters of the electrospun PLGA nanofibers were characterized using scanning electron microscopy (SEM) and confocal Raman imaging. The surface chemistry of the PLGA nanofibers conjugated with the biotin–(PEG) 7 –amine was confirmed through time-of-flight secondary ion mass spectrometry (ToF–SIMS) imaging. The chip system was studied for the effects of the surface modification density of biotin–(PEG) 7 –amine, the flow rates, and the diameters of the PLGA nanofibers on the capture efficiency of EpCAM-positive HCT116 cells from the spiked liquid samples. To assess their CTC capture efficiencies in whole blood samples, the aligned and random PLGA nanofiber arrays were tested for their abilities to capture HCT116 cells, providing cancer cell capture efficiencies of 66 and 80%, respectively. With the continuous injection of air foam into the microfluidic devices, the cell release efficiency on the aligned PLGA fibers was 74% (recovery rate: 49%), while it was 90% (recovery rate: 73%) on the random PLGA fibers, from tests of 200 spiked cells in 2 mL of whole blood from healthy individuals. Our study suggests that integrated PMMA microfluidic chips embedding random PLGA nanofiber arrays may be suitable devices for the efficient capture and recovery of CTCs from whole blood samples. Electronic supplementary material The online version of this article (10.1186/s12951-019-0466-2) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Random and aligned electrospun PLGA nanofibers embedded in microfluidic chips for cancer cell isolation and integration with air foam technology for cell release

Chen

Yeh

et al. 2019

J Nanobiotechnol

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“…Glutathione (GSH) and excess thiol molecules were utilized to competitively exchange original thiol ligands, resulting in CTC release with over 90% efficiency and 78% cell viability ( Figure 6 D). Shen et al reported a phenylboronic acid (PBA)-grafted PEDOT NanoVelcro chip with anti-EpCAM antibody conjugated onto the nanosubstrate of the chip via PBA–oligosaccharide binding [ 107 ]. The introduction of glycan with stronger affinity to PBA results in competitive binding, allowing effective CTC release.…”

Section: Nanotechnology-assisted Circulating Tumor Cell (Ctc) Isolmentioning

confidence: 99%

Nanotechnology-Assisted Isolation and Analysis of Circulating Tumor Cells on Microfluidic Devices

et al. 2020

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Circulating tumor cells (CTCs), a type of cancer cell that spreads from primary tumors into human peripheral blood and are considered as a new biomarker of cancer liquid biopsy. It provides the direction for understanding the biology of cancer metastasis and progression. Isolation and analysis of CTCs offer the possibility for early cancer detection and dynamic prognosis monitoring. The extremely low quantity and high heterogeneity of CTCs are the major challenges for the application of CTCs in liquid biopsy. There have been significant research endeavors to develop efficient and reliable approaches to CTC isolation and analysis in the past few decades. With the advancement of microfabrication and nanomaterials, a variety of approaches have now emerged for CTC isolation and analysis on microfluidic platforms combined with nanotechnology. These new approaches show advantages in terms of cell capture efficiency, purity, detection sensitivity and specificity. This review focuses on recent progress in the field of nanotechnology-assisted microfluidics for CTC isolation and detection. Firstly, CTC isolation approaches using nanomaterial-based microfluidic devices are summarized and discussed. The different strategies for CTC release from the devices are specifically outlined. In addition, existing nanotechnology-assisted methods for CTC downstream analysis are summarized. Some perspectives are discussed on the challenges of current methods for CTC studies and promising research directions.

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“…Forming more stable chemical bonds by introducing ligand with stronger affinities is an alternative strategy of ligand‐competition release. Thereinto, boronic acid modified interfaces have attracted much interest for cell capture‐and‐release, since the formed cyclic esters between boronic acid with 1,2‐ or 1,3‐diols of oligosaccharide could be replaced by glycan . For example, Yu and co‐workers reported a glycan‐stimulated and phenylboronic acid (PBA)‐grafted nanosubstrate platform to purify prostate cancer CTCs .…”

Section: Ctc Releasementioning

confidence: 99%

Beyond Capture: Circulating Tumor Cell Release and Single‐Cell Analysis

Sharma

et al. 2019

Small Methods

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As the most promising “liquid biopsy”, analysis of circulating tumor cells (CTCs) provides noninvasive access to obtain biological information of solid tumors. It not only advances the understanding of the mechanisms underlying tumor metastasis, relapse, and chemoresistance, but also promotes the development of precision medicine. Over the past decade, the rapid advances in micro/nanomaterials and microfluidics have overcome the technical challenges of capturing CTCs, allowing efficient enrichment and sensitive detection. Beyond the capture of CTCs, major challenges of in‐depth CTC analysis are the release of CTCs from capture platforms and the inherent heterogeneity in CTCs. A variety of technologies have now emerged for release and single‐cell analysis of CTCs. This review focuses on recent progress along this direction. First, different release strategies are outlined and discussed, including their design principles and characteristics (merits and limitations). Then, existing methods for single CTC analysis at the genomic, transcriptomic, proteomic, and functional level are summarized. Finally, some perspectives are provided on current development trends, future research directions, and challenges of CTC studies.

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Glycan Stimulation Enables Purification of Prostate Cancer Circulating Tumor Cells on PEDOT NanoVelcro Chips for RNA Biomarker Detection

Cited by 43 publications

References 74 publications

Random and aligned electrospun PLGA nanofibers embedded in microfluidic chips for cancer cell isolation and integration with air foam technology for cell release

Random and aligned electrospun PLGA nanofibers embedded in microfluidic chips for cancer cell isolation and integration with air foam technology for cell release

Nanotechnology-Assisted Isolation and Analysis of Circulating Tumor Cells on Microfluidic Devices

Beyond Capture: Circulating Tumor Cell Release and Single‐Cell Analysis

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