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

A glycan-stimulated and poly(3,4-ethylene-dioxythiophene)s (PEDOT)-based nanomaterial platform is fabricated to purify circulating tumor cells (CTCs) from blood samples of prostate cancer (PCa) patients. This new platform, phenylboronic acid (PBA)-grafted PEDOT NanoVelcro, combines the 3D PEDOT nanosubstrate, which greatly enhances CTC capturing efficiency, with a poly(EDOT-PBA-co-EDOT-EG3) interfacial layer, which not only provides high specificity for CTC capture upon antibody conjugation but also enables competitive binding of sorbitol to gently release the captured cells. CTCs purified by this PEDOT NanoVelcro chip provide well-preserved RNA transcripts for the analysis of the expression level of several PCa-specific RNA biomarkers, which may provide clinical insights into the disease.

Poly(3,4-ethylenedioxythiophene)-Based Nanofiber Mats as an Organic Bioelectronic Platform for Programming Multiple Capture/Release Cycles of Circulating Tumor Cells.

In this investigation, we employed a novel one-step electrospinning process to fabricate poly(ethylene oxide) (PEO)/poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) core/shell nanofiber structures with improved water resistance and good electrochemical properties and characterized them using scanning electron microscopy, transmission electron microscopy, and time-of-flight secondary ion mass spectrometry imaging. We then integrated a biotinylated poly-(l-lysine-graft-ethylene glycol) (PLL-g-PEG-biotin) coating with three-dimensional (3D) PEDOT-based nanofiber devices for dynamic control over the capture/release performance of rare circulating tumor cells (CTCs) on-chip. The detailed capture/release behavior of the circulating tumor cells was studied using an organic bioelectronic platform comprising PEO/PEDOT:PSS nanofiber mats with 3 wt % (3-glycidyloxypropyl)trimethoxysilane as an additive. We have demonstrated that these nanofiber mats deposited on five-patterned indium tin oxide finger electrodes are excellent candidates for use as functional bioelectronic interfaces for the isolation, detection, sequential collection, and enrichment of rare CTCs through electrical activation of each single electrode. This combination behaved as an ideal model system displaying a high cell-capture yield for antibody-positive cells while resisting the adhesion of antibody-negative cells. Taking advantage of the electrochemical doping/dedoping characteristics of PEDOT:PSS materials, the captured rare cells could be electrically triggered release through the desorption phenomena of PLL-g-PEG-biotin on device surface. More than 90% of the targeted cancer cells were captured on the 3D PEDOT-based nanofiber microfluidic device; over 87% of captured cancer cells were subsequently released for collection; approximately 80% of spiked cancer cells could be collected in a 96-well plate. Therefore, this 3D PEDOT-based nanofiber approach appears to be an economical route for the large-scale preparation of systems for enhancing the downstream characterization of rare CTCs.

Integrated 3D conducting polymer-based bioelectronics for capture and release of circulating tumor cells.

Here we develop a novel fabrication approach for producing three-dimensional (3D) conducting polymer-based bioelectronic interfaces (BEIs) that can be integrated on electronic devices for rare circulating tumor cell (CTC) isolation, detection, and collection via an electrically triggered cell released from chips. Based on the chemical oxidative polymerization of carboxylic acid-modified 3,4-ethylenedioxythiophene and modified poly(dimethylsiloxane) (PDMS) transfer printing technology, the high-aspect-ratio structures of poly(3,4-ethylenedioxythiophene) (PEDOT)-based "nanorod" arrays can be fabricated on indium tin oxide (ITO) electrodes when using the Si "microrod" arrays as masters. Furthermore, we integrated the biotinylated poly-(l)-lysine-graft-poly-ethylene-glycol (PLL-g-PEG-biotin) coating with 3D PEDOT-based BEIs for dynamic control of the capture/release performance of CTCs on chips; this combination exhibited an optimal cell-capture yield cells of ∼45 000 cells cm-2 from EpCAM-positive MCF7 while maintaining resistance from the adhesion of EpCAM-negative HeLa cells at a density of ∼4000 cells cm-2. By taking advantage of the electrochemical doping/dedoping properties of PEDOT materials, the captured CTCs can be triggered to be electrically released through the desorption phenomena of the PLL-g-PEG-biotin. More than 90% of the captured cells can be released while maintaining very high cell viability. Therefore, it is conceivable that the use of a 3D PEDOT-based BEI platform will meet the requirements for the development of downstream characterization of CTCs, as well as the next generation of bioelectronics for biomedical applications.