Haichao Zhao

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.

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.

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.

Oligoethylene-glycol-functionalized polyoxythiophenes for cell engineering: syntheses, characterizations, and cell compatibilities.

A series of methyl- or benzyl-capped oligoethylene glycol functionalized 2,5-dibromo-3-oxythiophenes are synthesized and successfully polymerized by either Grignard metathesis (GRIM) polymerization or reductive coupling polymerization to yield the corresponding polymers in reasonable yields and molecular weights with narrow molecular weight distribution. These synthesized polyoxythiophenes exhibit high electroactivity and stability in aqueous solution when a potential is applied. Polyoxythiophenes from different polymerization approaches display different colors after purification and spectroelectrochemical studies confirm that the difference of color is from the difference of doping state. Little cytotoxicity is observed for the polymers by in vitro cell compatibility assay. NIH3T3 fibroblast cells are well attached and proliferate on spin-coated films. These results indicate that oligoethylene-glycol-functionalized polyoxythiophenes are promising candidates as conducting biomatierals for biomedical and bioengineering applications.

Step-Economical Syntheses of Functional BODIPY-EDOT π-Conjugated Materials through Direct C–H Arylation

Palladium-catalyzed direct C-H arylations of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) with 3,4-ethylenedioxythiophene (EDOT) derivatives at relatively low temperature (60 °C) provide moderate to good yields (47%-72%) of products having potential applications in fluorescent bioimaging and organic optoelectronics.

In vitro selection of peptide aptamers using a ribosome display for a conducting polymer.

Ribosome display was used to select peptide aptamers from a random library composed of hydrophilic amino acids for a conducting polymer, poly(3-hexylthiophene-2,5-diyl). Binding of aptamers was measured by quartz crystal microbalance, and the secondary structure of the peptide was investigated by circular dichroism.