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Electrochemical devices that transform electrical energy to mechanical energy through an electrochemical process have numerous applications ranging from soft robotics and micropumps to autofocus microlenses and bioelectronics. To date, achievement of large deformation strains and fast response times remains a challenge for electrochemical actuator devices operating in liquid wherein drag forces restrict the actuator motion and electrode materials/structures limit the ion transportation and accumulation. We report results for electrochemical actuators, electrochemical mass transfers, and electrochemical dynamics made from organic semiconductors (OSNTs). Our OSNTs electrochemical device exhibits high actuation performance with fast ion transport and accumulation and tunable dynamics in liquid and gel-polymer electrolytes. This device demonstrates an excellent performance, including low power consumption/strain, a large deformation, fast response, and excellent actuation stability. This outstanding performance stems from enormous effective surface area of nanotubular structure that facilitates ion transport and accumulation resulting in high electroactivity and durability. We utilize experimental studies of motion and mass transport along with the theoretical analysis for a variable–mass system to establish the dynamics of the electrochemical device and to introduce a modified form of Euler-Bernoulli’s deflection equation for the OSNTs. Ultimately, we demonstrate a state-of-the-art miniaturized device composed of multiple microactuators for potential biomedical application. This work provides new opportunities for next generation electrochemical devices that can be utilized in artificial muscles and biomedical devices.

Functional nerve recovery after the injury is crucial in the field of neural interfaces. Although numerous technologies have already been established to promote nerve regeneration, effective nerve guidance in long distances (over 10 mm) still remains challenging. Herein, we report a novel technique to fabricate long gradients of substrate-bound laminin protein on conducting polymer films of poly(3,4-ethylenedioxythiophene) (PEDOT). The developed methodology allows for creation of various gradient profiles of laminin on PEDOT films to modulate axonal regeneration. These bioactive and conductive platforms can potentially be employed to promote axonal regeneration in the long nerve gaps.

This paper describes the preparation and characterization of polymeric nanoparticles loaded with a potent anti-tumor metal chelator, Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) for delivery to cancer cells. Metal chelators have been increasingly studied for their anti-cancer properties that rely on the high demand of neoplastic cells for iron. Dp44mT has previously shown great antiproliferative characteristics in several cancers including breast cancer and melanoma. To further expand the application of this highly cytotoxic agent for cancer treatment and to enable its specific delivery to malignant cells, here we apply nano-scale particles (NPs) of biodegradable poly(lactic-co-glycolide) (PLGA) for encapsulation of Dp44mT and evaluate its effectiveness in vitro. The results demonstrated that Dp44mT was efficiently encapsulated in PLGA particles. Resulting NPs were uniform in size and shape and had good colloidal stability. Moreover, Dp44mT encapsulation in PLGA enhanced the water solubility of this agent. Lastly, the present formulation showed high level of cytotoxicity in glioma cells. Together, these results show the potential of PLGA NPs as a nano-carrier for Dp44mT with no apparent impact on the anti-tumor activity of this compound.

Conducting polymers (CPs) are easy to process and have tunable physical and chemical properties including conductivity, volume, color, and hydrophobicity. Therefore, these organic polymers are attractive in a broad spectrum of bioelectronic applications ranging from implantable electrodes to biosensors and actuators. Patterned films of CPs, especially with various surface chemistries, provide versatile and sophisticated building-blocks for bioelectronics. In this context, we recently introduecd a simple and efficinet technique of hydrogel-mediated electropolymerization to directly pattern films of PPy (polypyrrole) with spatially-addressable chemistries. This technique employs a topographically patterned hydrogel stamp to deliver polymer precursors to the surface of electrode during the PPy electropolymerization. This method enables easy incorporation of different molecules into CP film during the polymerization. Herein, we aim to extend the scope of hydrogel-mediated electropolymerization to pattern other types of CPs and to explore the potential of bio-functionalized CP films for cell adhesion studies. Using this method, patterned films of two distinct CPs, PPy and PEDOT, were generated with a number of dopants. The produced films were characterized for morphology, impedance, and chemical composition. Patterned CP films were bio-functionalized by incorporation of a lamimin peptide into these films. Lastly, the resultant substartes were tested for cell adhesion where laminin-doped CP showed a higher level of cell adhesion compared to PSS (polystyrene sulfonate)-doped CP films. These results together demonstrate the potential application of patterned films of bio-functionalized CPs for cellular engineering.

A new methodology for selective electropolymerization of conducting polymer films using wet hydrogel stamps is presented. The ability of this simple method to generate patterned films of conducting polymers with multiple surface chemistries in a one-step process and to incorporate fragile biomolecules in these films is demonstrated.

Synthetic nanopores have been used to study individual biomolecules in high throughput, but their performance as sensors does not match that of biological ion channels. Challenges include control of nanopore diameters and surface chemistry, modification of the translocation times of single-molecule analytes through nanopores, and prevention of non-specific interactions with pore walls. Here, inspired by the olfactory sensilla of insect antennae, we show that coating nanopores with a fluid lipid bilayer tailors their surface chemistry and allows fine-tuning and dynamic variation of pore diameters in subnanometre increments. Incorporation of mobile ligands in the lipid bilayer conferred specificity and slowed the translocation of targeted proteins sufficiently to time-resolve translocation events of individual proteins. Lipid coatings also prevented pores from clogging, eliminated non-specific binding and enabled the translocation of amyloid-beta (Aβ) oligomers and fibrils. Through combined analysis of their translocation time, volume, charge, shape and ligand affinity, different proteins were identified.

Biological protein pores and pore-forming peptides can generate a pathway for the flux of ions and other charged or polar molecules across cellular membranes. In nature, these nanopores have diverse and essential functions that range from maintaining cell homeostasis and participating in cell signaling to activating or killing cells. The combination of the nanoscale dimensions and sophisticated - often regulated - functionality of these biological pores make them particularly attractive for the growing field of nanobiotechnology. Applications range from single-molecule sensing to drug delivery and targeted killing of malignant cells. Potential future applications may include the use of nanopores for single strand DNA sequencing and for generating bio-inspired, and possibly, biocompatible visual detection systems and batteries. This article reviews the current state of applications of pore-forming peptides and proteins in nanomedicine, sensing, and nanoelectronics.

Organic electronic materials are rapidly emerging as superior replacements for a number of conventional electronic materials, such as metals and semiconductors. Conducting polymers, carbon nanotubes, graphenes, organic light-emitting diodes, and diamond films fabricated via chemical vapor deposition are the most popular organic bioelectronic materials that are currently under active research and development. Besides the capability to translate biological signals to electrical signals or vice versa, organic bioelectronic materials entail greater biocompatibility and biodegradability compared to conventional electronic materials, which makes them more suitable for biomedical applications. When patterned, these materials bring about numerous capabilities to perform various tasks in a more-sophisticated and high-throughput manner. Here, we provide an overview of the unique properties of organic bioelectronic materials, different strategies applied to pattern these materials, and finally their applications in the field of biomedical engineering, particularly biosensing, cell and tissue engineering, actuators, and drug delivery.

Bioinspired artificial water channels aim to combine the high permeability and selectivity of biological aquaporin (AQP) water channels with chemical stability. Here, we carefully characterized a class of artificial water channels, peptide-appended pillar[5]arenes (PAPs). The average single-channel osmotic water permeability for PAPs is 1.0(± 0.3) × 10(-14) cm(3)/s or 3.5(± 1.0) × 10(8) water molecules per s, which is in the range of AQPs (3.4 ∼ 40.3 × 10(8) water molecules per s) and their current synthetic analogs, carbon nanotubes (CNTs, 9.0 × 10(8) water molecules per s). This permeability is an order of magnitude higher than first-generation artificial water channels (20 to ∼ 10(7) water molecules per s). Furthermore, within lipid bilayers, PAP channels can self-assemble into 2D arrays. Relevant to permeable membrane design, the pore density of PAP channel arrays (∼ 2.6 × 10(5) pores per μm(2)) is two orders of magnitude higher than that of CNT membranes (0.1 ∼ 2.5 × 10(3) pores per μm(2)). PAP channels thus combine the advantages of biological channels and CNTs and improve upon them through their relatively simple synthesis, chemical stability, and propensity to form arrays.

Giant proteoliposomes mimic natural cell membranes and provide excellent models for membrane biophysical studies such as membrane phase separation, lipid-protein interactions, and functional studies of membrane proteins. Here, we present a simple and versatile approach for producing a large number of uniformly-sized giant proteoliposomes in a parallel fashion. This approach that combines the versatile technique of hydrogel-based microcontact printing and the commonly used technique of electroformation is efficient, low-cost, and doesn't require any specialized equipment. The resulting liposomes are attached to the surface in an array format, enabling rapid data collection for statistical analysis of membrane processes. We applied these vesicles for monitoring lipid-protein and protein-protein binding interactions. Alternatively, liposomes can be easily detached from the surface to produce a large number of giant liposomes with functional membrane proteins. We employed these vesicles for studying the channel activity of aquaporin protein and for monitoring material transport across lipid membranes. This approach may further be applicable to produce giant polymerosomes with increased stability compared to liposomes. The presented method can, hence, be useful in biomaterials, biotechnology, and biosensing applications as well as in the biophysical fundamental studies.View Large Image | View Hi-Res Image | Download PowerPoint Slide

A simple and versatile method for the Formation of Arrays of Giant Vesicles with Controlled Size and Composition. The ability of this technique to generate arrays of giant liposomes from a wide range of membrane lipids and protein compositions is demonstrated. The resulting vesicles are utilized for studying protein activity, lipid-protein interactions, and protein-protein interactions.

This work introduces the concept of synthetic nanopores with fluid lipid walls and describes the benefit of these pores for single protein translocation experiments. The inspiration for this design comes from lipid-coated nanopores in olfactory sensilla of insect antennae. Multifunctional coatings of fluid lipids enable characterization of single proteins with unprecedented information content and address currently unmet challenges of single protein investigations with nanopores. For instance, translocation events of lipid-anchored proteins reveal the charge, ligand affinity, volume, and molecular shape of single proteins in high throughput. Moreover, translocation of amyloidogenic peptides through a pore with fluid walls makes it possible to characterize a large number of individual Alzheimer's disease-related amyloid-beta fibrils in situ; these fibrils clog conventional nanopores. The choice of lipids in the coating makes it possible to fine-tune the thickness, surface chemistry, functionality, and viscosity of the coating in the pore. These characteristics enable increasing the signal to noise ratio, eliminating non-specific binding, capturing and concentrating specific analytes, increasing translocation times, and time-resolving translocation events completely. Finally, these coatings provide the exquisite sensitivity to monitor thermally-induced conformational changes in bimolecular sheets of lipids and these phase transitions make it possible to actuate the diameters of synthetic nanopore dynamically in situ.

This research introduces the concept of coating the surfaces of nanopores with supported lipid bilayers for previously inaccessible nanopore-based assays. Current methods for shrinking nanopores with nanometer precision entail the use of specialized instruments such as focused ion beams or electron beams. Furthermore, altering the surface chemistry of nanopores currently requires multiple chemical steps and typically takes longer than one day. The method presented here modifies the surface chemistry of nanopores within 90 min by deposition of desired lipids with various chemical headgroups. This work also demonstrates the use of lipids with acyl chains of different lengths to shrink the diameter of a nanopore with sub-nanometer precision. Remarkably, the surface of bilayer-coated nanopores is non-fouling and makes it possible to detect aggregates of the "notoriously sticky" peptide, amyloid-β; the same nanopore without a bilayer clogged in every experiment. These non-fouling properties of nanopores coated with a fluid lipid bilayer made it possible to resolve single aggregates of amyloid-β and to characterize their true size distribution. Finally, this research took advantage of bilayer-coated nanopores to monitor the activity of the membrane-active enzyme, phospholipase D. Together the results presented here demonstrate that supported lipid bilayers can be used to alter the size and surface chemistry of nanopores reversibly. Moreover, bilayer-coated nanopores show promise to study membrane-active enzymes, membrane processes, as well as to perform nano-Coulter counter experiments on peptides that aggregate and adhere to surfaces such as amyloid-β.

Giant unilamellar vesicles (GUVs) are attractive model membranes, commonly used to study membrane processes such as membrane fusion and protein-lipid interactions. Arrays of GUVs are, therefore, ideal platforms for high-throughput screening of such processes. Here, we present a simple approach to form arrays of GUVs with or without membrane-proteins. This approach combines hydrogel-based microcontact printing with the commonly-used electroformation technique to generate arrays of GUVs with controllable size and composition. First, micro-patterned agarose stamps deliver aqueous solutions of small liposomes/proteoliposomes onto conductive substrates. GUVs are then produced from these patterned deposits using electroformation. By varying the feature size of stamps, we controlled the number of liposomes grown per deposit and ultimately formed single-vesicle arrays with a narrow size distribution (37±1μm diameter). We demonstrated this method's capability to create giant proteoliposome arrays by electroforming vesicles from stamped aquaporin-containing membrane deposits, and acetylcholine receptor-containing cell membrane fragments and confirmed the presence of these proteins by immunofluorescent-assays. We further illustrated the versatility of this approach by forming GUV arrays in physiologically-relevant solutions. To demonstrate this system's applicability for studying protein-lipid interactions, we investigated the interactions of a membrane-associated protein, annexin-V, with phosphatidylserine-containing GUVs.View Large Image | View Hi-Res Image | Download PowerPoint Slide