Transdermal Sensing of Enzyme Biomarker Enabled by Chemo-Responsive Probe-Modified Epidermal Microneedle Patch in Human Skin Tissue.

Wearable bioelectronics represents a significant breakthrough in healthcare settings, particularly in (bio)sensing which offers an alternative way to track individual health for diagnostics and therapy. However, there has been no notable improvement in the field of cancer, particularly for skin cancer. Here, a wearable bioelectronic patch is established for transdermal sensing of the melanoma biomarker, tyrosinase (Tyr), using a microneedle array integrated with a surface-bound chemo-responsive smart probe to enable target-specific electrochemical detection of Tyr directly from human skin tissue. The results presented herein demonstrate the feasibility of a transdermal microneedle sensor for direct quantification of enzyme biomarkers in an ex vivo skin model. Initial performance analysis of the transdermal microneedle sensor proves that the designed methodology can be an alternative for fast and reliable diagnosis of melanoma and the evaluation of skin moles. The innovative approach presented here may revolutionize the landscape of skin monitoring by offering a nondisruptive means for continuous surveillance and timely intervention of skin anomalies, such as inflammatory skin diseases or allergies and can be extended to the screening of multiple responses of complementary biomarkers with simple modification in device design.

Nano-Impact Single-Entity Electrochemistry Enables Plasmon-Enhanced Electrocatalysis.

Plasmon-enhanced electrocatalysis (PEEC), based on a combination of localized surface plasmon resonance excitation and an electrochemical bias applied to a plasmonic material, can result in improved electrical-to-chemical energy conversion compared to conventional electrocatalysis. Here, we demonstrate the advantages of nano-impact single-entity electrochemistry (SEE) for investigating the intrinsic activity of plasmonic catalysts at the single-particle level using glucose electrooxidation and oxygen reduction on gold nanoparticles as model reactions. We show that in conventional ensemble measurements, plasmonic effects have minimal impact on photocurrents. We suggest that this is due to the continuous equilibration of the Fermi level (EF ) of the deposited gold nanoparticles with the EF of the working electrode, leading to fast neutralization of hot carriers by the measuring circuit. The photocurrents detected in the ensemble measurements are primarily caused by photo-induced heating of the supporting electrode material. In SEE, the EF of suspended gold nanoparticles is unaffected by the working electrode potential. As a result, plasmonic effects are the dominant source of photocurrents under SEE experimental conditions.

Current Progress of Interfacing Organic Semiconducting Materials with Bacteria.

Microbial bioelectronics require interfacing microorganisms with electrodes. The resulting abiotic/biotic platforms provide the basis of a range of technologies, including energy conversion and diagnostic assays. Organic semiconductors (OSCs) provide a unique strategy to modulate the interfaces between microbial systems and external electrodes, thereby improving the performance of these incipient technologies. In this review, we explore recent progress in the field on how OSCs, and related materials capable of charge transport, are being used within the context of microbial systems, and more specifically bacteria. We begin by examining the electrochemical communication modes in bacteria and the biological basis for charge transport. Different types of synthetic organic materials that have been designed and synthesized for interfacing and interrogating bacteria are discussed next, followed by the most commonly used characterization techniques for evaluating transport in microbial, synthetic, and hybrid systems. A range of applications is subsequently examined, including biological sensors and energy conversion systems. The review concludes by summarizing what has been accomplished so far and suggests future design approaches for OSC bioelectronics materials and technologies that hybridize characteristic properties of microbial and OSC systems.

Bacterial Sensing and Biofilm Monitoring for Infection Diagnostics.

Recent insights into the rapidly emerging field of bacterial sensing and biofilm monitoring for infection diagnostics are discussed as well as recent key developments and emerging technologies in the field. Electrochemical sensing of bacteria and bacterial biofilm via synthetic, natural, and engineered recognition, as well as direct redox-sensing approaches via algorithm-based optical sensing, and tailor-made optotracing technology are discussed. These technologies are highlighted to answer the very critical question: "how can fast and accurate bacterial sensing and biofilm monitoring be achieved? Following on from that: "how can these different sensing concepts be translated for use in infection diagnostics? A central obstacle to this transformation is the absence of direct and fast analysis methods that provide high-throughput results and bio-interfaces that can control and regulate the means of communication between biological and electronic systems. Here, the overall progress made to date in building such translational efforts at the level of an individual bacterial cell to a bacterial community is discussed.

Wearable Organic Electrochemical Transistor Patch for Multiplexed Sensing of Calcium and Ammonium Ions from Human Perspiration.

Wearable health monitoring has garnered considerable interest from the healthcare industry as an evolutionary alternative to standard practices with the ability to provide rapid, off-site diagnosis and patient-monitoring. In particular, sweat-based wearable biosensors offer a noninvasive route to continuously monitor a variety of biomarkers for a range of physiological conditions. Both the accessibility and wealth of information of sweat make it an ideal target for noninvasive devices that can aid in early diagnosis of disease or to monitor athletic performance. Here, the integration of ammonium (NH4+ ) and calcium (Ca2+ ) ion-selective membranes with a poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)-based (PEDOT:PSS) organic electrochemical transistor (OECT) for multiplexed sensing of NH4+ and Ca2+ in sweat with high sensitivity and selectivity is reported for the first time. The presented wearable sweat sensor is designed by combining a flexible and stretchable styrene-ethylene-butene-styrene substrate with a laser-patterned microcapillary channel array for direct sweat acquisition and delivery to the ion-selective OECT. The resulting dermal sensor exhibits a wide working range between 0.01 × 10-3 and 100 × 10-3 m, well within the physiological levels of NH4+ and Ca2+ in sweat. The integrated devices are successfully implemented with both ex situ measurements and on human subjects with real-time analysis using a wearable sensor assembly.

Molecularly selective nanoporous membrane-based wearable organic electrochemical device for noninvasive cortisol sensing.

Wearable biosensors have emerged as an alternative evolutionary development in the field of healthcare technology due to their potential to change conventional medical diagnostics and health monitoring. However, a number of critical technological challenges including selectivity, stability of (bio)recognition, efficient sample handling, invasiveness, and mechanical compliance to increase user comfort must still be overcome to successfully bring devices closer to commercial applications. We introduce the integration of an electrochemical transistor and a tailor-made synthetic and biomimetic polymeric membrane, which acts as a molecular memory layer facilitating the stable and selective molecular recognition of the human stress hormone cortisol. The sensor and a laser-patterned microcapillary channel array are integrated in a wearable sweat diagnostics platform, providing accurate sweat acquisition and precise sample delivery to the sensor interface. The integrated devices were successfully used with both ex situ methods using skin-like microfluidics and on human subjects with on-body real-sample analysis using a wearable sensor assembly.

Organic Electronics for Point-of-Care Metabolite Monitoring.

In this review we focus on demonstrating how organic electronic materials can solve key problems in biosensing thanks to their unique material properties and implementation in innovative device configurations. We highlight specific examples where these materials solve multiple issues related to complex sensing environments, and we benchmark these examples by comparing them to state-of-the-art commercially available sensing using alternative technologies. We have categorized our examples by sample type, focusing on sensing from body fluids in vitro and on wearable sensors, which have attracted significant interest owing to their integration with everyday life activities. We finish by describing a future trend for in vivo, implantable sensors, which aims to build on current progress from sensing in biological fluids ex vivo.

Structuring Au nanoparticles on two-dimensional MoS2 nanosheets for electrochemical glucose biosensors.

Two-dimensional (2D) bioelectronics is an emerging field of research which fuses the advantages of 2D nanomaterials with those of nanobiotechnology. Due to the various physical and chemical properties present in layered counterparts of 2D materials, including high charge density, large surface area, remarkable electron mobility, ready electron transport, sizeable band gaps and ease of hybridisation, they are set to become a versatile tool to fabricate sensitive and selective novel biodevices, which might offer an unique advantages to tackle key energy, medical and environmental issues. Current 2D bioelectronics research is focused on the design of simple-to-use and cheaper biodevices, while improving their selectivity, sensitivity and stability. However, current designs generally suffer from a lack of efficiency, relatively low sensitivity, slow electron transfer kinetics, high background charging current and low current density arising from poor mass transport. Here, we report a nanoparticle-structured MoS2 nanosheet as an ideal semiconductor interface, which is able to form a homogenous layer on the electrode surface for the assembly of gold nanoparticles. This not only enhances electrocatalytic reactions, but also provides excellent electrochemical properties such as high faradic-to-capacitive current ratios, high current density and electron mobility, and faster mass transport, due to the dominance of radial diffusion. The MoS2/Au NPs/GOx bioelectrode exhibits a linear response to glucose from 0.25 to 13.2mM, with a detection limit of 0.042µM (S/N=3) and sensitivity of 13.80µA/µM/cm2.

Acetylene-sourced CVD-synthesised catalytically active graphene for electrochemical biosensing.

In this study, we have demonstrated the use of chemical vapour deposition (CVD) grown-graphene to develop a highly-ordered graphene-enzyme electrode for electrochemical biosensing. The graphene sheets were deposited on 1.00mm thick copper sheet at 850°C using acetylene (C2H2) as carbon source in an argon (Ar) and nitrogen (N2) atmosphere. An anionic surfactant was used to increase wettability and hydrophilicity of graphene; thereby facilitating the assembly of biomolecules on the electrode surface. Meanwhile, the theoretical calculations confirmed the successful modification of hydrophobic nature of graphene through the anionic surface assembly, which allowed high-ordered immobilisation of glucose oxidase (GOx) on the graphene. The electrochemical sensing activities of the graphene-electrode was explored as a model for bioelectrocatalysis. The bioelectrode exhibited a linear response to glucose concentration ranging from 0.2 to 9.8mM, with sensitivity of 0.087µA/µM/cm2 and a detection limit of 0.12µM (S/N=3). This work sets the stage for the use of acetylene-sourced CVD-grown graphene as a fundamental building block in the fabrication of electrochemical biosensors and other bioelectronic devices.

Programmable bioelectronics in a stimuli-encoded 3D graphene interface.

The ability to program and mimic the dynamic microenvironment of living organisms is a crucial step towards the engineering of advanced bioelectronics. Here, we report for the first time a design for programmable bioelectronics, with 'built-in' switchable and tunable bio-catalytic performance that responds simultaneously to appropriate stimuli. The designed bio-electrodes comprise light and temperature responsive compartments, which allow the building of Boolean logic gates (i.e."OR" and "AND") based on enzymatic communications to deliver logic operations.

Switchable bioelectronics.

We review the rapidly emerging field of switchable interfaces and its implications for bioelectronics. We seek to piece together early breakthroughs and key developments, and highlight and discuss the future of switchable bioelectronics by focusing on bio-electrochemical processes based on mimicking and controlling biological environments with external stimuli. All these studies strive to answer a fundamental question: "how do living systems probe and respond to their surroundings? And, following on from that: "how one can transform these concepts to serve the practical world of bioelectronics?" The central obstacle to this vision is the absence of versatile interfaces that are able to control and regulate the means of communication between biological and electronic systems. Here, we review the overall progress made to date in building such interfaces at the level of individual biomolecules and focus on the latest efforts to generate device platforms that integrate bio-interfaces with electronics.

Null Extinction of Ceria@silica Hybrid Particles: Transparent Polystyrene Composites.

Scattering of light in optical materials, particularly in composites based on transparent polymer and inorganic pigment nanoparticles, is a chronic problem. It might originate mainly from light scattering because of a refractive index mismatch between the particles and transparent polymer matrix. Thus, the intensity of light is rapidly diminished and optical transparency is reduced. Refractive index matching between the pigment core and the surrounding transparent matrix using a secondary component at the interface (shell) has recently appeared as a promising approach to alter light scattering. Here, CeO2 (ceria) nanoparticles with a diameter of 25 nm are coated with a SiO2 (silica) shell with various thicknesses in a range of 6.5-67.5 nm using the Stöber method. When the hybrid core-shell particles are dispersed into transparent polystyrene (PS), the transmission of the freestanding PS composite films increases over both the ultraviolet (UV) and visible region as the shell thickness increases particularly at 37.5 nm. The increase of transmission can be attributed to the reduction in the scattering coefficient of the hybrid particles. On the other hand, the particles in tetrahydrofuran (THF) absorb over UV and the intensity of absorption shows a systematic decrease as the shell thickness increases. Thus, the silica shell suppresses not only the scattering coefficient but also the molar absorptivity of the core ceria particles. The experimental results regarding the target shell thickness to develop low extinction (scattering + absorption) composites show a qualitative agreement with the predictions of Effective Medium Theory.

Switchable Bioelectrocatalysis Controlled by Dual Stimuli-Responsive Polymeric Interface.

The engineering of bionanointerfaces using stimuli-responsive polymers offers a new dimension in the design of novel bioelectronic interfaces. The integration of electrode surfaces with stimuli-responsive molecular cues provides a direct control and ability to switch and tune physical and chemical properties of bioelectronic interfaces in various biodevices. Here, we report a dual-responsive biointerface employing a positively responding dual-switchable polymer, poly(NIPAAm-co-DEAEMA)-b-HEAAm, to control and regulate enzyme-based bioelectrocatalysis. The design interface exhibits reversible activation-deactivation of bioelectrocatalytic reactions in response to change in temperature and in pH, which allows manipulation of biomolecular interactions to produce on/off switchable conditions. Using electrochemical measurements, we demonstrate that interfacial bioelectrochemical properties can be tuned over a modest range of temperature (i.e., 20-60 °C) and pH (i.e., pH 4-8) of the medium. The resulting dual-switchable interface may have important implications not only for the design of responsive biocatalysis and on-demand operation of biosensors, but also as an aid to elucidating electron-transport pathways and mechanisms in living organisms by mimicking the dynamic properties of complex biological environments and processes.

pH-induced on/off-switchable graphene bioelectronics.

Switchable interfaces can deliver functionally reversible reactivity with their corresponding analytes, which allows one to positively respond to the activity of biological elements, including enzymes and other biomolecules, through an encoded stimulus. We have realized this by the design of stimuli-responsive graphene interfaces for the pH-encoded operation of bioelectronics. Herein, we have demonstrated stimuli-responsive graphene interfaces for the pH-encoded operation of bioelectronics. The resulting switchable interfaces are capable of the highly specific, on-demand operation of biosensors, which has significant potential in a wide range of analytical applications.

On/Off-switchable zipper-like bioelectronics on a graphene interface.

An on/off-switchable graphene-based zipper-like interface is architectured for efficient bioelectrocatalysis. The graphene interface transduces a temperature input signal into structural changes of the membrane, resulting in the amplification of electrochemical signals and their transformation into the gated transport of molecules through the membrane.

Template-directed hierarchical self-assembly of graphene based hybrid structure for electrochemical biosensing.

A template-directed self-assembly approach, using functionalised graphene as a fundamental building block to obtain a hierarchically ordered graphene-enzyme-nanoparticle bioelectrode for electrochemical biosensing, is reported. An anionic surfactant was used to prepare a responsive, functional interface and direct the assembly on the surface of the graphene template. The surfactant molecules altered the electrostatic charges of graphene, thereby providing a convenient template-directed assembly approach to a free-standing planar sheet of sp(2) carbons. Cholesterol oxidase and cholesterol esterase were assembled on the surface of graphene by intermolecular attractive forces while gold nanoparticles are incorporated into the hetero-assembly to enhance the electro-bio-catalytic activity. Hydrogen peroxide and cholesterol were used as two representative analytes to demonstrate the electrochemical sensing performance of the graphene-based hybrid structure. The bioelectrode exhibited a linear response to H2O2 from 0.01 to 14 mM, with a detection limit of 25 nM (S/N=3). The amperometric response with cholesterol had a linear range from 0.05 to 0.35 mM, sensitivity of 3.14 µA/µM/cm(2) and a detection limit of 0.05 µM. The apparent Michaelis-Menten constant (Km(app)) was calculated to be 1.22 mM. This promising approach provides a novel methodology for template-directed bio-self-assembly over planar sp(2) carbons of a graphene sheet and furnishes the basis for fabrication of ultra-sensitive and efficient electrochemical biosensors.

Toward transparent nanocomposites based on polystyrene matrix and PMMA-grafted CeO2 nanoparticles.

The association of transparent polymer and nanosized pigment particles offers attractive optical materials for various potential and existing applications. However, the particles embedded into polymers scatter light due to refractive index (RI) mismatch and reduce transparency of the resulting composite material. In this study, optical composites based on polystyrene (PS) matrix and poly(methyl methacrylate) (PMMA)-grafted CeO(2) hybrid particles were prepared. CeO(2) nanoparticles with an average diameter of 18 ± 8 nm were precipitated by treating Ce(NO(3))·6H(2)O with urea in the presence of a polymerizable surfactant, 3-methacyloxypropyltrimethoxy silane. PMMA chains were grafted on the surface of the nanoparticles upon free radical in situ solution polymerization. While blending of unmodified CeO(2) particles with PS resulted in opaque films, the transparency of the composite films was remarkably enhanced when prepared by PMMA-grafted CeO(2) hybrid particles, particularly those having a PMMA thickness of 9 nm. The improvement in transparency is presumably due to the reduction in RI mismatch between CeO(2) particles and the PS matrix when using PMMA chains at the interface.

Intestinal vaginoplasty: seven years' experience of a tertiary center.

OBJECTIVE: To investigate the long-term effects of intestinal vaginoplasty in cases with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. DESIGN: Prospective study. SETTING: Division of Pelvic Reconstructive Surgery, Department of Gynecology and Obstetrics, at a women's and children disease education and research hospital. PATIENT(S): Between 2003 and 2009, 29 patients with MRKH syndrome underwent intestinal vaginoplasty. INTERVENTION(S): Two of the patients were treated with ileal and 27 with sigmoid vaginoplasty. MAIN OUTCOME MEASURE(S): The age, marital status, associated anomalies, method used for bowel transposition (isoperistaltic/antiperistaltic), type of abdominal incision, and intra- and postoperative complications were evaluated. RESULT(S): One of the patients for whom ileal vaginoplasty was performed had 40 cm ileal necrosis requiring bilateral ileostomy for 2 months. Introital stenosis was detected in 15 cases (79%) who were unmarried, while none of the married cases had introital stenosis. However, all patients responded to finger-dilatation. All married patients were sexually satisfied after operation. An intraluminal abscess developed in the proximal segment of the neovagina owing to stricture occurring above abdominoperineal tunnel 2 years after operation. In another patient who had a rudimentary uterine horn, hematometra developed 3 years after operation and treated with resection. CONCLUSION(S): In our experience, sigmoid vaginoplasty seems to be a favorable procedure which provides excellent long-term results for the patients with vaginal agenesis.