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

Abstract

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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“…Characteristic features of the Raman spectra for pristine carbon can be observed at 1580 cm −1 (G band) and 2700 cm −1 (2D band) [31]. Raman peaks near 875 and 925 cm −1 are caused by extensions to the inside of C-O-C symmetric stretching, and the one near 1455 cm −1 is caused by -COO [32,33]. The Raman spectrum of PPG exhibited strong peaks at 2883 and 2939 cm −1 , corresponding to stretching vibrations of the alkyl chains [34,35].…”

Nanomaterial-Based Immunocapture Platforms for the Recognition, Isolation, and Detection of Circulating Tumor Cells

“…After GSH treatment, the Au-S bond on the surface of micropillars was easily disrupted so that the release of CTCs reached 80% with 96% viability. In addition to PDMS-based microfluidic chips, cheaper poly(methyl methacrylate)–based microfluidic chips also have the potential for the capture and recovery of CTCs from whole blood samples ( Yu et al, 2019 ), in which nanomaterials can still be grown in the microchannels to improve the isolation performance.…”

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“…373 8b). 363 Another study reports the encapsulation of two antibacterial drugs, Irgasan and levofloxacin, within electrospun PCL fibers and drug localization within the fibrous membrane via ToF-SIMS analysis. 389 ToF-SIMS is often used in combination with XPS results due to its increased surface sensitivity for obtaining information about the lateral resolution.…”

“…(b) ToF-SIMS chemical imaging of PEGylated biotin-conjugated PLGA nanofibers. This image is reprinted with permission from ref . Copyright 2019 Springer Nature.…”