In Situ Observations of Nanofibril Nucleation and Growth during the Electrochemical Polymerization of Poly(3,4-ethylenedioxythiophene) Using Liquid-Phase Transmission Electron Microscopy.

The electrochemical deposition of poly(3,4-ethylenedioxythiophene) (PEDOT) has been carried out previously in the presence of a variety of counterions. Previous studies have shown that elongated nanofibrillar structures of PEDOT would form reproducibly when certain counterions such as poly(acrylic acid) (PAA) were added to the reaction mixture. However, details of the nanofibril nucleation and growth stages were not yet clear. Here, we describe the structural evolution of PEDOT nanofibrils using liquid-phase transmission electron microscopy (LPTEM). We measured the growth velocities of nanofibrils in different directions at various stages of the process and their intensity profiles, and we have estimated the number of EDOT monomers involved. We observed that fibrils initially grew anisotropically in a direction nominally perpendicular to the local edge of the electrodes, with rates that were faster along their lengths as compared those along to their widths and thicknesses. These real-time observations have helped us elucidate the nucleation and growth of PEDOT nanofibrils during electrochemical deposition.

Si-thiol supported atomic-scale palladium as efficient and recyclable catalyst for Suzuki coupling reaction.

Atomic-scale catalysts leverage the advantages of both heterogeneous catalysts for their stability and reusability and homogeneous catalysts for their isolated active sites. Here, a palladium catalyst supported by Si-thiol, a commercially available mercaptopropyl-modified and TMS-passivated amorphous silica, was synthesized and characterized by SEM,TEM, aberration-corrected STEM-HAADF, XRD, FT-IR and XPS. Statistical analysis revealed that the catalytic Pd species predominantly consisted of intermediate sized nanoparticles (<2 nm), small amounts of essentially isolated atoms (ca. 0.1 nm), and limited amounts of somewhat larger nanoparticles (<5 nm). The nanoscale atomic clusters dominated the reactivity and served as the key active sites for Suzuki coupling. The outcomes of the reaction were greatly affected by the choice of solvents, and Pd/Si-thiol was demonstrated to be reusable for more than three times without a noticeable loss of catalytic activity. [Formula: see text].

Nanoarchitecturing of Natural Melanin Nanospheres by Layer-by-Layer Assembly: Macroscale Anti-inflammatory Conductive Coatings with Optoelectronic Tunability.

Natural melanins are biocompatible conductors with versatile functionalities. Here, we report fabrication of multifunctional poly(vinyl alcohol)/melanin nanocomposites by layer-by-layer (LBL) assembly using melanin nanoparticles (MNPs) directly extracted from sepia officinalis inks. The LBL assembly offers facile manipulation of nanotextures as well as nm-thickness control of the macroscale film by varying solvent qualities. The time-resolved absorption was monitored during the process and quantitatively studied by fractal dimension and lacunarity analysis. The capability of nanoarchitecturing provides confirmation of complete monolayer formation and leads to tunable iridescent reflective colors of the MNP films. In addition, the MNP films have durable electrochemical conductivities as evidenced by enhanced charge storage capacities for 1000 cycles. Moreover, the MNP covered ITO (indium tin oxide) substrates significantly reduced secretion of inflammatory cytokines, TNF-α, by raw 264.7 macrophage cells compared to bare ITO, by a factor of 5 and 1.8 with and without lipopolysaccharide endotoxins, respectively. These results highlight the optoelectronic device-level tunability along with the anti-inflammatory biocompatibility of the MNP LBL film. This combination of performance should make these films particularly interesting for bioelectronic device applications such as electroceuticals, artificial bionic organs, biosensors, and implantable devices.

Single Electrospun PLLA and PCL Polymer Nanofibers: Increased Molecular Orientation with Decreased Fiber Diameter.

Electrospinning has become a widely-used method for fabricating polymer nanofibers for various applications including filtration, drug delivery, and tissue engineering. Due to the high extensional forces during the electrospinning process, and the rapid crystallization and solidification during solvent evaporation, molecular orientation may develop within the resulting fibers. The properties of electrospun fibers are expected to be sensitive to level of orientation in the fibers. Various reports have shown an increased modulus with decreased fiber diameter, and molecular orientation has been used to explain this trend. However, there have been relatively few studies of the detailed relationship between fiber diameter and molecular orientation, especially at the single fiber level. Here we report a quantitative study of the orientation in individual electrospun poly(caprolactone) (PCL) and poly(L-lactic acid) (PLLA) fibers using low-dose electron microscopy and diffraction techniques. Our results confirmed that for electrospun fibers of PCL and PLLA processed under similar experimental conditions, the molecular orientation decreased as the fiber diameter increased. The extent of orientation remained high for quite large fiber diameters, with azimuthal orientation of 20 degrees seen up to ~500 nm for PCL and ~2000 nm for PLLA.

Synthesis and characterization of bicontinuous cubic poly(3,4-ethylene dioxythiophene) gyroid (PEDOT GYR) gels.

We describe the synthesis and characterization of bicontinuous cubic poly(3,4-ethylenedioxythiophene) (PEDOT) conducting polymer gels prepared within lyotropic cubic poly(oxyethylene)10 nonylphenol ether (NP-10) templates with Ia3[combining macron]d (gyroid, GYR) symmetry. The chemical polymerization of EDOT monomer in the hydrophobic channels of the NP-10 GYR phase was initiated by AgNO3, a mild oxidant that is activated when exposed to ultraviolet (UV) radiation. The morphology and physical properties of the resulting PEDOT gels were examined as a function of temperature and frequency using optical and electron microscopy, small-angle X-ray scattering (SAXS), dynamic mechanical spectroscopy, and electrochemical impedance spectroscopy (EIS). Microscopy and SAXS results showed that the PEDOT gels remained ordered and stable after the UV-initiated chemical polymerization, confirming the successful templated-synthesis of PEDOT in bicontinuous GYR nanostructures. In comparison to unpolymerized 3,4-ethylenedioxythiophene (EDOT) gel phases, the PEDOT structures had a higher storage modulus, presumably due to the formation of semi-rigid PEDOT-rich nanochannels. Additionally, the storage modulus (G') for PEDOT gels decreased only modestly with increasing temperature, from ∼1.2 × 10(5) Pa (10 °C) to ∼7 × 10(4) Pa (40 °C), whereas G' for the NP-10 and EDOT gels decreased dramatically, from ∼5.0 × 10(4) Pa (10 °C) to ∼1.5 × 10(2) Pa (40 °C). EIS revealed that the impedance of the PEDOT gels was smaller than the impedance of EDOT gels at both high frequencies (PEDOT ∼10(2) Ω and EDOT 2-3 × 10(4) Ω at 10(5) Hz) and low frequencies (PEDOT 10(3)-10(5) Ω and EDOT ∼5 × 10(5) Ω at 10(-1) Hz). These results indicated that PEDOT gels were highly ordered, mechanically stable and electrically conductive, and thus should be of interest for applications for which such properties are important, including low impedance and compliant coatings for biomedical electrodes.

Synthesis, copolymerization and peptide-modification of carboxylic acid-functionalized 3,4-ethylenedioxythiophene (EDOTacid) for neural electrode interfaces.

BACKGROUND: Conjugated polymers have been developed as effective materials for interfacing prosthetic device electrodes with neural tissue. Recent focus has been on the development of conjugated polymers that contain biological components in order to improve the tissue response upon implantation of these electrodes. METHODS: Carboxylic acid-functionalized 3,4-ethylenedioxythiophene (EDOTacid) monomer was synthesized in order to covalently bind peptides to the surface of conjugated polymer films. EDOTacid was copolymerized with EDOT monomer to form stable, electrically conductive copolymer films referred to as PEDOT-PEDOTacid. The peptide GGGGRGDS was bound to PEDOT-PEDOTacid to create peptide functionalized PEDOT films. RESULTS: The PEDOT-PEDOTacid-peptide films increased the adhesion of primary rat motor neurons between 3 and 9 times higher than controls, thus demonstrating that the peptide maintained its biological activity. CONCLUSIONS: The EDOT-acid monomer can be used to create functionalized PEDOT-PEDOTacid copolymer films that can have controlled bioactivity. GENERAL SIGNIFICANCE: PEDOT-PEDOTacid-peptide films have the potential to control the behavior of neurons and vastly improve the performance of implanted electrodes. This article is part of a Special Issue entitled Organic Bioelectronics-Novel Applications in Biomedicine.

Influence of Controlled Chirality on the Crystallization of Maleimide-Functionalized 3,4-Ethylenedioxythiophene (EDOT-MA) Monomers.

Conjugated poly(alkoxythiophenes) such as poly(3,4-ethylenedioxythiophene) (PEDOT) have attracted considerable interest for use in a variety of applications such as biomedical devices, energy storage, and chemical sensing. Functionalized versions of the 3,4-ethylenedioxythiophene (EDOT) monomer make it possible to create polymers with properties tailored for specific applications. The maleimide functional group shows particular promise due to the wide variety of chemical modifications that it can undergo. Here, we examine the role that control of the chirality of the maleimide (MA) substituent has on the crystal structure and crystallization of the EDOT-MA monomer. We describe a method for the synthesis of a homochiral (S) variant of EDOT-MA and compare its crystallography, morphology, and thermal properties to that of the (R,S) EDOT-MA racemic compound. The conformation of the EDOT-MA molecule was substantially different, with the molecules adopting an "L" shape in the homochiral crystal, while in the racemic crystals, they were more colinear. The thermal stability of the homochiral crystals (Tm = 128.6 °C) was slightly higher than the racemic ones (Tm = 102.8 °C). We expect these results to be important in better understanding the solid-state assembly of the corresponding polymers prepared from these monomers.

Imidazolium-Based Sulfonating Agent to Control the Degree of Sulfonation of Aromatic Polymers and Enable Plastics-to-Electronics Upgrading.

The accumulation of plastic waste in the environment is a growing environmental, economic, and societal challenge. Plastic upgrading, the conversion of low-value polymers to high-value materials, could address this challenge. Among upgrading strategies, the sulfonation of aromatic polymers is a powerful approach to access high-value materials for a range of applications, such as ion-exchange resins and membranes, electronic materials, and pharmaceuticals. While many sulfonation methods have been reported, achieving high degrees of sulfonation while minimizing side reactions that lead to defects in the polymer chains remains challenging. Additionally, sulfonating agents are most often used in large excess, which prevents precise control over the degree of sulfonation of aromatic polymers and their functionality. Herein, we address these challenges using 1,3-disulfonic acid imidazolium chloride ([Dsim]Cl), a sulfonic acid-based ionic liquid, to sulfonate aromatic polymers and upgrade plastic waste to electronic materials. We show that stoichiometric [Dsim]Cl can effectively sulfonate model polystyrene up to 92% in high yields, with minimal defects and high regioselectivity for the para position. Owing to its high reactivity, the use of substoichiometric [Dsim]Cl uniquely allows for precise control over the degree of sulfonation of polystyrene. This approach is also applicable to a wide range of aromatic polymers, including waste plastic. To prove the utility of our approach, samples of poly(styrene sulfonate) (PSS), obtained from either partially sulfonated polystyrene or expanded polystyrene waste, are used as scaffolds for poly(3,4-ethylenedioxythiophene) (PEDOT) to form the ubiquitous conductive material PEDOT:PSS. PEDOT:PSS from plastic waste is subsequently integrated into organic electrochemical transistors (OECTs) or as a hole transport layer (HTL) in a hybrid solar cell and shows the same performance as commercial PEDOT:PSS. This imidazolium-mediated approach to precisely sulfonating aromatic polymers provides a pathway toward upgrading postconsumer plastic waste to high-value electronic materials.

Highly Aligned Poly(3,4-ethylene dioxythiophene) (PEDOT) Nano- and Microscale Fibers and Tubes.

This study reports a facile method for the fabrication of aligned Poly(3,4-ethylene dioxythiophene) (PEDOT) fibers and tubes based on electrospinning and oxidative chemical polymerization. Discrete PEDOT nano- and microfibers and nano- and microtubes are difficult to fabricate quickly and reproducibly. We employed poly(lactide-co-glycolide) (PLGA) polymers that were loaded with polymerizable 3,4-ethylene dioxythiophene (EDOT) monomer to create aligned nanofiber assemblies using a rotating glass mandrel during electrospinning. The EDOT monomer/PLGA polymer blends were then polymerized by exposure to an oxidative catalyst (FeCl3). PEDOT was polymerized by continuously dripping a FeCl3 solution onto the glass rod during electrospinning. The resulting PEDOT fibers were conductive, aligned and discrete. Fiber bundles could be easily produced in lengths of several centimeters. The PEDOT sheath/PLGA core fibers were immersed in chloroform to remove the PLGA and any residual EDOT resulting in hollow PEDOT tubes. This approach made it possible to easily generate large areas of aligned PEDOT fibers/tubes. The structure and properties of the aligned assemblies were measured using optical microscopy, electron microscopy, Raman spectroscopy, thermal gravimetric analysis, and DC conductivity measurements. We also demonstrated that the aligned PEDOT sheath/PLGA core fiber assemblies could be used in supporting and directing the extension of dorsal root ganglia (DRG) neurons in vitro.

Morphological and dimensional control via hierarchical assembly of doped oligoaniline single crystals.

Single crystals of doped aniline oligomers are produced via a simple solution-based self-assembly method. Detailed mechanistic studies reveal that crystals of different morphologies and dimensions can be produced by a "bottom-up" hierarchical assembly where structures such as one-dimensional (1-D) nanofibers can be aggregated into higher order architectures. A large variety of crystalline nanostructures including 1-D nanofibers and nanowires, 2-D nanoribbons and nanosheets, 3-D nanoplates, stacked sheets, nanoflowers, porous networks, hollow spheres, and twisted coils can be obtained by controlling the nucleation of the crystals and the non-covalent interactions between the doped oligomers. These nanoscale crystals exhibit enhanced conductivity compared to their bulk counterparts as well as interesting structure-property relationships such as shape-dependent crystallinity. Furthermore, the morphology and dimension of these structures can be largely rationalized and predicted by monitoring molecule-solvent interactions via absorption studies. Using doped tetraaniline as a model system, the results and strategies presented here provide insight into the general scheme of shape and size control for organic materials.

Patterning of periodic nano-cavities on PEDOT-PSS using nanosphere-assisted near-field optical enhancement and laser interference lithography.

A simple approach for creating periodic nano-cavities and periodic stripes of nano-cavity arrays on poly (3,4-ethylene dioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) thin films using a combination of optical near-field enhancement through self-assembled silica nanospheres and laser interference lithography is presented. Monolayers of close-packed silica nanospheres (800, 600, and 430 nm in diameter) are self-assembled on 2 µm thick PEDOT-PSS electropolymerized films and are subsequently irradiated with 10 ns pulses of 355 nm wavelength laser light. Over areas spanning 2 cm(2), circular nano-cavities with central holes of size 50-200 nm and surrounding craters of size 100-400 nm are formed in the PEDOT-PSS films directly underneath the nanospheres due to strong enhancement (11-18 fold) of the incident light in the near-field, which is confirmed through Mie scattering theory. Predictions from theoretical simulations examining the combined effects of near-field enhancement and interference are in good agreement with the experimental results. The results illustrate the versatility of the described technique for creating nano-cavity arrays or nano-pores in PEDOT-PSS over large areas with designed periodicity and hole size.

Electrochemical Fabrication and Characterization of Organic Electrochemical Transistors Using poly(3,4-ethylenedioxythiophene) with Various Counterions.

Organic electrochemical transistors (OECTs) are promising bioelectronic devices, especially because of their ability to transport charge both ionically and electronically. Conductive polymers are typically used as the active materials of OECTs. Crosslinked, cast, and dried films of commercially available poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) suspensions are commonly and widely used for OECTs so far. Electrochemical polymerization of PEDOT from 3,4-ethylenedioxythiophene (EDOT) monomer can also be used to fabricate OECTs; however, this approach has not been investigated in as much detail. In particular, the role of various counterions that can be incorporated into the PEDOT films of OECTs has not been systematically studied. Here, we report the electrochemical fabrication and characterization of OECTs using PEDOT with several different counterion salts including lithium perchlorate (LiClO4), sodium p-toluene sulfonate (pTS), and poly(sodium 4-styrene sulfonate) (PSS). We found that the characteristic dimensions of PEDOT films deposited on the electrodes could be precisely controlled by total charge density, with a nominal thickness of about one micron requiring a current density of about 0.6 C/cm2 regardless of the choice of counterion. The films with the PSS counterion were relatively smooth, while PEDOT films prepared with the pTS and LiClO4 were much rougher due to the sizes of counterions. The PEDOT films with pTS and PSS grew along the substrate surface (in-plane direction) much faster than with LiClO4. The maximum transconductance (gm) of a PEDOT OECT was 46 mS with pTS as the counterion with the high on-current level (>10 mA) based on the large channel area. These results provide an effective and efficient way to fabricate OECTs with various monomers and additives as active materials in order to modify the device characteristics for further applications.

Influence of the molecular weight and size distribution of PSS on mixed ionic-electronic transport in PEDOT:PSS.

The commercially available polyelectrolyte complex poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) is ubiquitous in organic and hybrid electronics. As such, it has often been used as a benchmark material for fundamental studies and the development of new electronic devices. Yet, most studies on PEDOT:PSS have focused on its electronic conductivity in dry environments, with less consideration given to its ion transport, coupled ionic-electronic transport, and charge storage properties in aqueous environments. These properties are essential for applications in bioelectronics (sensors, actuators), charge storage devices, and electrochromic displays. Importantly, past studies on mixed ionic-electronic transport in PEDOT:PSS neglected to consider how the molecular structure of PSS affects mixed ionic-electronic transport. Herein, we therefore investigated the effect of the molecular weight and size distribution of PSS on the electronic properties and morphology of PEDOT:PSS both in dry and aqueous environments, and overall performance in organic electrochemical transistors (OECTs). Using reversible addition-fragmentation chain transfer (RAFT) polymerization with two different chain transfer agents, six PSS samples with monomodal, narrow (D = 1.1) and broad (D = 1.7) size distributions and varying molecular weights were synthesized and used as matrices for PEDOT. We found that using higher molecular weight of PSS (M n = 145 kg mol-1) and broad dispersity led to OECTs with the highest transconductance (up to 16 mS) and [µC * ] values (~140 F·cm-1V-1s-1) in PEDOT:PSS, despite having a lower volumetric capacitance (C * = 35 ± 4 F cm-3). The differences were best explained by studying the microstructure of the films by atomic force microscopy (AFM). We found that heterogeneities in the PEDOT:PSS films (interconnected and large PEDOT- and PSS-rich domains) obtained from high molecular weight and high dispersity PSS led to higher charge mobility (µ OECT ~ 4 cm2V-1s-1) and hence transconductance. These studies highlight the importance of considering molecular weight and size distribution in organic mixed ionic-electronic conductor, and could pave the way to designing high performance organic electronics for biological interfaces.

Structural, chemical and electrochemical characterization of poly(3,4-ethylenedioxythiophene) (PEDOT) prepared with various counter-ions and heat treatments.

Electrochemical deposition of the conjugated polymer poly(3,4-ethylenedioxythiophene) (PEDOT) forms thin, conductive films that are especially suitable for charge transfer at the tissue-electrode interface of neural implants. For this study, the effects of counter-ion choice and annealing parameters on the electrical and structural properties of PEDOT were investigated. Films were polymerized with various organic and inorganic counter-ions. Studies of crystalline order were conducted via X-ray diffraction (XRD). Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) were used to investigate the electrical properties of these films. X-ray photoelectron spectroscopy (XPS) was used to investigate surface chemistry of PEDOT films. The results of XRD experiments showed that films polymerized with certain small counter-ions have a regular structure with strong (100) edge-to-edge correlations of PEDOT chains at ~1.3 nm. After annealing at 170 °C for 1 hour, the XRD peaks attributed to PEDOT disappeared. PEDOT polymerized with LiClO(4) as a counter-ion showed improved impedance and charge storage capacity after annealing at 160 °C.

Conducting-polymer nanotubes improve electrical properties, mechanical adhesion, neural attachment, and neurite outgrowth of neural electrodes.

An in vitro comparison of conducting-polymer nanotubes of poly(3,4-ethylenedioxythiophene) (PEDOT) and poly(pyrrole) (PPy) and to their film counterparts is reported. Impedance, charge-capacity density (CCD), tendency towards delamination, and neurite outgrowth are compared. For the same deposition charge density, PPy films and nanotubes grow relatively faster vertically, while PEDOT films and nanotubes grow more laterally. For the same deposition charge density (1.44 C cm(-2)), PPy nanotubes and PEDOT nanotubes have lower impedance (19.5 +/- 2.1 kOmega for PPy nanotubes and 2.5 +/- 1.4 kOmega for PEDOT nanotubes at 1 kHz) and higher CCD (184 +/- 5.3 mC cm(-2) for PPy nanotubes and 392 +/- 6.2 mC cm(-2) for PEDOT nanotubes) compared to their film counterparts. However, PEDOT nanotubes decrease the impedance of neural-electrode sites by about two orders of magnitude (bare iridium 468.8 +/- 13.3 kOmega at 1 kHz) and increase capacity of charge density by about three orders of magnitude (bare iridium 0.1 +/- 0.5 mC cm(-2)). During cyclic voltammetry measurements, both PPy and PEDOT nanotubes remain adherent on the surface of the silicon dioxide while PPy and PEDOT films delaminate. In experiments of primary neurons with conducting-polymer nanotubes, cultured dorsal root ganglion explants remain more intact and exhibit longer neurites (1400 +/- 95 microm for PPy nanotubes and 2100 +/- 150 microm for PEDOT nanotubes) than their film counterparts. These findings suggest that conducting-polymer nanotubes may improve the long-term function of neural microelectrodes.

Continuous delivery of biomaterials to the skin-percutaneous device interface using a fluid pump.

We have developed an in vitro culture system composed of organotypic human skin explants interfaced with titanium rods attached to a fluid pump. This device was designed to mimic the process of natural mucosa delivery at the point where a rigid, permanent object penetrates living skin. Full thickness human breast skin explants discarded from surgeries were cultured at different time points at the air-liquid interface. The skin specimens were punctured to fit at the bottom of hollow cylindrical titanium rods. Sodium lauryl sulfate (SLS) was delivered continuously to the specimens through the rods by using an attached fluid pump. Histological analysis of the skin explants as well as no-pump controls was then performed. Our results show substantial differences between controls, where no material was pumped at the interface of rod-skin, and specimens treated with SLS, indicating that the technique of pumping the material is effective in producing observable epithelial changes. These results suggest that an adaptation of this type of device may be useful for the treatment of complications arising from the contact between tissues and percutaneous devices in vivo.

Layered carbon nanotube-polyelectrolyte electrodes outperform traditional neural interface materials.

The safety, function, and longevity of implantable neuroprosthetic and cardiostimulating electrodes depend heavily on the electrical properties of the electrode-tissue interface, which in many cases requires substantial improvement. While different variations of carbon nanotube materials have been shown to be suitable for neural excitation, it is critical to evaluate them versus other materials used for bioelectrical interfacing, which have not been done in any study performed so far despite strong interest to this area. In this study, we carried out this evaluation and found that composite multiwalled carbon nanotube-polyelectrolyte (MWNT-PE) multilayer electrodes substantially outperform in one way or the other state-of-the-art neural interface materials available today, namely activated electrochemically deposited iridium oxide (IrOx) and poly(3,4-ethylenedioxythiophene) (PEDOT). Our findings provide the concrete experimental proof to the much discussed possibility that carbon nanotube composites can serve as excellent new material for neural interfacing with a strong possibility to lead to a new generation of implantable electrodes.

Electrically conducting polymers for bio-interfacing electronics: From neural and cardiac interfaces to bone and artificial tissue biomaterials.

Conductive polymers (CPs) are gaining considerable attention as materials for implantable bioelectronics due to their unique features such as electronic-ionic hybrid conductivity, mechanical softness, ease of chemical modification, as well as moderate biocompatibility. CPs have been utilized for a wide range of applications including neural engineering, regenerative medicine, multi-functional sensors and actuators. This review focuses on CP materials design for use in bio-interfacing electronics including composites, conductive hydrogels, and electrochemical deposition. We start by elaborating on the fundamental materials characteristics of CPs, including bio-electrochemical charge-transfer mechanisms, and contrast them with naturally derived CPs. We then present recent critical examples of the bioelectronic and biomedical applications of CPs, including neural recording and stimulation, tissue regeneration, stretchable electronics, and mechanical actuation. We conclude with a perspective of the current material challenges of CPs in bio-interfacing electronics.

Impedimetric Biosensors for Detecting Vascular Endothelial Growth Factor (VEGF) Based on Poly(3,4-ethylene dioxythiophene) (PEDOT)/Gold Nanoparticle (Au NP) Composites.

In advanced forms of diabetic retinopathy, retinal vascular occlusive disease and exudative age-related macular degeneration, vision loss is associated with elevated levels or extravasation of vascular endothelial-derived growth factor (VEGF) into the retina, vitreous, and anterior chamber of the eye. We hypothesize that point-of-care biosensors, capable of rapidly and precisely measuring VEGF levels within the eye will assist clinicians in assessing disease severity, and in establishing individualized dosing intervals for intraocular anti-VEGF injection therapy. An impedance biosensor based on a poly(3,4-ethylenedioxythiophene) (PEDOT)/gold nanoparticle (Au NP) composite was developed for detecting VEGF. PEDOT with Au NP was electrochemically deposited on three different medical electrode sensor designs: free-standing pads, screen printed dots, and interdigitated micro-strip electrodes. Anti-VEGF antibody was covalently immobilized on the surface of the polymer films through attachment to citrate-functionalized Au NPs, and the resulting composites were used to detect VEGF-165 by electrochemical impedance spectroscopy (EIS). The PEDOT-Au NP composite materials were characterized using optical microscopy, SEM/EDS, FIB, TEM, and STEM techniques. Among the different micro-electrodes, the interdigitated strip shape showed the best overall film stability and reproducibility. A linear relationship was established between the charge transfer resistance (R ct ) and VEGF concentration. The detection limit of VEGF was found to be 0.5 pg/mL, with a correlation coefficient of 0.99 ± 0.064%. These results indicate that the proposed PEDOT/Au NP composites can be used in designing low-cost and accurate VEGF biosensors for applications such as clinical diagnosis of VEGF-mediated eye disease.

Durability of Poly(3,4-ethylenedioxythiophene) (PEDOT) films on metallic substrates for bioelectronics and the dominant role of relative shear strength.

Despite growing interest in the use of conducting polymer coatings such as poly(3,4-ethylenedioxythiophene) (PEDOT) in bioelectronics, their relatively poor mechanical durability on inorganic substrates has limited long-term and clinical applications. Efforts to enhance durability have been limited by the lack of quantifiable metrics that can be used to evaluate the polymer film integrity and associated device failure. Here we examine the hypothesis that film failure under the tribological and cyclic electrical stressing becomes substantially less likely when the interfacial shear strength (τi) exceeds the shear strength of the film (τf). In this paper, we: (1) develop a simple yet robust method to quantify the relative shear strength (τi/τf); (2) quantify the effect of substrate and surface treatment on the relative shear strength of PEDOT; (3) relate changes in relative shear strength to resistance to interface failure under cyclic electrical and tribological testing. Treating a stainless-steel substrate with an adhesion promoter increased τi/τf from 0.18 to 0.69 compared to untreated controls. On untreated gold, the τi/τf of PEDOT increased to 1.46. Whereas both cyclic electrical and tribological testing quickly and severely damaged the interface of PEDOT when τi/τf < 1, neither stimulus had any quantifiable effect on delamination when τi/τf > 1.