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

Abstract

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.

Application of electrochemical biosensors in tumor cell detection

“…In 2007, Nagrath and coworkers used a microfluidic chip modified with an epithelial‐specific adhesion molecule (EpCAM) antibody to successfully separate untreated peripheral blood CTCs for the first time . At present, the microfluidic chip based on an antibody as the trapping probe has successfully detected CTCs . At the same time, as an artificial small molecule that is easier to preserve and modify than antibodies, the aptamer is more suitable for functional modification of microfluidic chips.…”

“…79 At present, the microfluidic chip based on an antibody as the trapping probe has successfully detected CTCs. [80][81][82][83] At the same time, as an artificial small molecule that is easier to preserve and modify than antibodies, the aptamer is more suitable for functional modification of microfluidic chips. For example, the microfluidic chip modified by nucleic acid aptamer sgc8 has successfully achieved the separation and capture of target cells from many samples with a capture efficiency of 80% and a specificity greater than 97%.…”

On the Interaction between 1D Materials and Living Cells

“…PEDOT-based micro/nanorod arrays have also been processed as a 3D bioelectronic interface, by using a combination of chemical oxidative polymerization and modified PDMS transfer printing [ 205 ] to produce a device capturing EpCam-positive cancer cells at 90% efficiency. PEDOT electrospun fibres mats have been demonstrated as powerful tumour cell capturing devices [ 206 ] based on the ordered deposition of biotinylated poly- l -lysine (PLL) PEG conjugate, SA, and anti-EpCAM-biotin. An electrically triggered detachment of the captured cells was achieved by applying cyclovoltammetric sweeps, reaching efficiencies as high as 87% ( Figure 10 e,f).…”

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

“…With a potential of −1.2 V to treat AuNWs for 30 s, 96.2% of the captured tumor cells were released with excellent cell viability of ≈90% ( Figure a). Conducting polymers, such as polypyrrole (Ppy), poly(3,4‐ethylenedioxythiophene) (PEDOT)], can be alternative conductive substrates for electrochemical cell release due to their predominant electrical transport and electrochemical charge–discharge properties, good biocompatibility, and high manufacturing flexibility . Cho and co‐workers developed biotin‐doped Ppy platform for the specific capture and controlled release of EpCAM‐positive tumor cells .…”