Hsiao-hua Yu

Poly(3,4-ethylenedioxythiophene) (PEDOT) Nanobiointerfaces : Thin, Ultrasmooth, and Functionalized PEDOT Films with in Vitro and in Vivo Biocompatibility

Nanobiointerfaces were prepared based on an electrically conductive polyethylenedioxythiophene (PEDOT). Thin (<100 nm), ultrasmooth (roughness ( R(rms)) < 5 nm), and functionalized PEDOT films have been successfully electropolymerized using aqueous microemulsion. The microemulsion polymerization is found to be catalyzed in the presence of a low concentration of acid and allows for film formation from various functionalized ethylenedioxythiophenes (EDOTs) (e.g., EDOT-OH, C(2)-EDOT-COOH, C(4)-EDOT-COOH, C(2)-EDOT-NHS, EDOT-N(3)) and their mixtures. The nanobiointerfaces are compositionally tunable and controlled to deposit on selected electrode surfaces. They prefer orthogonal growth on patterned surfaces and are synthesized within seconds. These thin PEDOT films exhibit very low intrinsic cytotoxicity and display no inflammatory response upon implantation, making them ideal for biosensing and bioengineering applications.

Capture and Stimulated Release of Circulating Tumor Cells on Polymer‐Grafted Silicon Nanostructures

A platform for capture and release of circulating tumor cells is demonstrated by utilizing polymer grafted silicon nanowires. In this platform, integration of ligand-receptor recognition, nanostructure amplification, and thermal responsive polymers enables a highly efficient and selective capture of cancer cells. Subsequently, these captured cells are released upon a physical stimulation with outstanding cell viability.

Functionalized Conducting Polymer Nanodots for Enhanced Cell Capturing: The Synergistic Effect of Capture Agents and Nanostructures

Many features of conducting polymers, including simplicity for nanostructure fabrication, tailored functional groups for bioconjugation, intrinsic electrical conductivity, and softer mechanical characteristics than metals, provide advantages as materials for cell-related diagnostic and therapeutic platforms. On the other hand, nanostructured materials have been recently reported with enhanced cell-capturing effi ciency. The enhanced performance are promising for fi nding cells of rare abundance in the blood stream with diagnostic potential, e.g., circulating tumor cells. [ 5–8 ] Here, we report our efforts on the creation of captureagent-functionalized conducting polymer nanodots and their effi cient capture on cells from a synergistic effect combining the ligand and nanostructure. Among all the conducting polymers, we are particularly interested in poly(3,4-ethylenedioxy)thiophenes (PEDOTs) [ 9 , 10 ]

Polydioxythiophene Nanodots, Nonowires, Nano-Networks, and Tubular Structures: The Effect of Functional Groups and Temperature in Template-Free Electropolymerization

Various nanostructures, including nanofibers, nanodots, nanonetwork, and nano- to microsize tubes of functionalized poly(3,4-ethylenedioxythiophene) (EDOT) and poly(3,4-propylenedioxythiophene) (ProDOT) are created by using a template-free electropolymerization method on indium-tin-oxide substrates. By investigating conducting polymer nanostructures containing various functional groups prepared at different polymerization temperature, we conclude a synergistic effect of functional groups and temperature on the formation of polymer nanostructures when a template-free electropolymerization method is applied. For unfunctionalized EDOT and ProDOT, or EDOT containing alkyl functional groups, nanofibers and nanoporous structures are usually found. Interesting, when polar functional groups are attached, conducting polymers tend to form nanodots at room temperature while grow tubular structures at low temperature. The relationship between surface properties and their nanostructures is evaluated by contact angle measurements. The capacity and electrochemical impedance spectroscopy measurements were conducted to understand the electrical properties of using these materials as electrodes. The results provide the relationship between the functional groups, nanostructures, and electrical properties. We also discuss the potential restriction of using this method to create nanostructures. The copolymerization of different functionalized EDOTs may cause irregular and unexpected nanostructures, which indicates the complex interaction between different functionalized monomers during the electropolymerization.

Perfluoro-functionalized PEDOT films with controlled morphology as superhydrophobic coatings and biointerfaces with enhanced cell adhesion

Perfluoro-functionalized PEDOT thin films with various surface morphologies were prepared electrochemically by applying different potential pulse sequences using ionic liquids as electrolyte and solvent, and these films could display superhydrophobicity with enhanced capability of cell adhesion.

Electric‐Field‐Assisted Growth of Functionalized Poly(3,4‐ethylenedioxythiophene) Nanowires for Label‐Free Protein Detection

The construction of functionalized poly(3,4-ethylenedioxythiophene) (PEDOT) nanowire devices for label-free protein detection is reported. Direct growth/assembly of PEDOT nanowires with carboxylic acid side-chain functional groups (poly(EDOT-COOH)) across the electrode junction is achieved by using an electric-field-assisted method. These functionalized PEDOT nanowire devices show typical depletion-mode p-type field-effect transistor (FET) properties. Upon conjugation with a protein-binding aptamer, the PEDOT nanowire FET devices are used for label-free electronic detection of a target protein of interest. The binding of a positively charged protein causes a substantial decrease in current flow, attributed to the specific interaction between target protein molecules and aptamer-conjugated polymer chains.

Programming thermoresponsiveness of NanoVelcro substrates enables effective purification of circulating tumor cells in lung cancer patients.

Unlike tumor biopsies that can be constrained by problems such as sampling bias, circulating tumor cells (CTCs) are regarded as the “liquid biopsy” of the tumor, providing convenient access to all disease sites, including primary tumor and fatal metastases. Although enumerating CTCs is of prognostic significance in solid tumors, it is conceivable that performing molecular and functional analyses on CTCs will reveal much significant insight into tumor biology to guide proper therapeutic intervention. We developed the Thermoresponsive NanoVelcro CTC purification system that can be digitally programmed to achieve an optimal performance for purifying CTCs from non-small cell lung cancer (NSCLC) patients. The performance of this unique CTC purification system was optimized by systematically modulating surface chemistry, flow rates, and heating/cooling cycles. By applying a physiologically endurable stimulation (i.e., temperature between 4 and 37 °C), the mild operational parameters allow minimum disruption to CTCs’ viability and molecular integrity. Subsequently, we were able to successfully demonstrate culture expansion and mutational analysis of the CTCs purified by this CTC purification system. Most excitingly, we adopted the combined use of the Thermoresponsive NanoVelcro system with downstream mutational analysis to monitor the disease evolution of an index NSCLC patient, highlighting its translational value in managing NSCLC.

Large enhancement in neurite outgrowth on a cell membrane-mimicking conducting polymer

Although electrically stimulated neurite outgrowth on bioelectronic devices is a promising means of nerve regeneration, immunogenic scar formation can insulate electrodes from targeted cells and tissues, thereby reducing the lifetime of the device. Ideally, an electrode material capable of electrically interfacing with neurons selectively and efficiently would be integrated without being recognized by the immune system and minimize its response. Here we develop a cell membrane-mimicking conducting polymer possessing several attractive features. This polymer displays high resistance towards nonspecific enzyme/cell binding and recognizes targeted cells specifically to allow intimate electrical communication over long periods of time. Its low electrical impedance relays electrical signals efficiently. This material is capable to integrate biochemical and electrical stimulation to promote neural cellular behaviour. Neurite outgrowth is enhanced greatly on this new conducting polymer; in addition, electrically stimulated secretion of proteins from primary Schwann cells can also occur on it.

Efficient synthesis of 3,4-ethylenedioxythiophene (EDOT)-based functional π-conjugated molecules through direct C-H bond arylations.

A variety of 3,4-ethylenedioxythiophene (EDOT)-based π-conjugated molecules were efficiently synthesized in good yields through Pd-catalyzed direct C-H bond arylations, wherein a detailed synthetic investigation, including the screening of various kinds of palladium catalysts, ligands, additives, and solvents, was carried out. In addition, the spectroscopic and electrochemical properties of these EDOT-containing molecules were also investigated.

Controlled Protein Absorption and Cell Adhesion on Polymer-Brush-Grafted Poly(3,4-ethylenedioxythiophene) Films

Tailoring the surface of biometallic implants with protein-resistant polymer brushes represents an efficient approach to improve the biocompability and mechanical compliance with soft human tissues. A general approach utilizing electropolymerization to form initiating group (-Br) containing poly(3,4-ethylenedioxythiophen)s (poly(EDOT)s) is described. After the conducting polymer is deposited, neutral poly((oligo(ethylene glycol) methacrylate), poly(OEGMA), and zwitterionic poly([2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide), poly(SBMA), brushes are grafted by surface-initiated atom transfer radical polymerization. Quartz crystal microbalance (QCM) experiments confirm protein resistance of poly(OEGMA) and poly(SBMA)-grafted poly(EDOT)s. The protein binding properties of the surface are modulated by the density of polymer brushes, which is controlled by the feed content of initiator-containing monomer (EDOT-Br) in the monomer mixture solution for electropolymerization. Furthermore, these polymer-grafted poly(EDOT)s also prevent cells to adhere on the surface.