Diamond like carbon coated films for enzyme electrodes; characterization of biocompatibility and substrate diffusion limiting properties

The biocompatibility and substrate diffusion limiting properties for a range of diamond like carbon (DLC) coated microporous polycarbonate and DLC coated dialysis (haemodialysis) membranes have been studied. This characterisation builds upon previous findings where DLC coated membranes imparted enhanced enzyme electrode performance. In this study electrode linear ranges have been extended from 10 mM glucose for a 0.01 μm pore size membrane to 160 mM. These findings correlated with the duration of DLC deposition and associated reductions in permeability for glucose. Permeability coefficient ratios for both microporous and dialysis membranes were also found to be important with low glucose/O₂ permeability ratios imparting extensions in glucose linear response range. DLC coated membranes employed within enzyme electrodes have also been shown to exhibit enhanced haemocompatibility as determined by both sensitivity change and surface deposition of blood components examined by scanning electron microscopy. Correlations are made between the reduced losses in sensor response to biofouling/ working electrode passivation processes, and extended linear ranges that DLC coated membranes may impart to enzyme electrode performance. Particular reference is made to the determination of glucose levels within whole blood.     

Optical Chemical Sensors Based on Sol-Gel Materials: Recent Advances and Critical Issues

The use of the sol-gel process to produce materials for optical chemical sensors and biosensors is attracting considerable interest. This interest derives mainly from the design flexibility of the sol-gel process and the ease of fabrication. In most applications the sol-gel material is used to provide a microporous support matrix in which analyte-sensitive species are entrapped and into which smaller analyte molecules may diffuse. Sensors based on entrapped organic and inorganic dyes, enzymes and other biomolecules have been reported. A range of sensor configurations has been employed, including monoliths, thin films, as well as more elaborate structures. In this paper a selection is presented of recent significant developments in optical chemical sensors which employ solgel-derived materials. These developments include the tailoring of sol-gel materials to optimise sensor response, advanced waveguide structures and novel probe-tip sensors. Those issues which remain critical to the eventual deployment of sol-gel sensors are examined. In particular, the problems of leaching, microstructural stability, diffusion-limited response time, and susceptibility to interferents are discussed and some solutions proposed.     

A fluorescent sensor with high selectivity and sensitivity for potassium in water

This communication describes a new optical sensor suitable for practical measurement of extracellular (serum or whole blood) potassium. The sensor responds rapidly and reversibly to changes in potassium concentrations typical of whole blood samples. No interferences from clinical concentrations of calcium or pH are observed, and the sodium interference is very minor. Excitation and emission occur in the visible light region. This new potassium sensor is currently used in the Roche OPTI CCA, a commercially available whole blood analyzer.     

Functionalized graphene-based biomimetic microsensor interfacing with living cells to sensitively monitor nitric oxide release

It is a great challenge to develop electrochemical sensors with superior sensitivity that concurrently possess high biocompatibility for monitoring at the single cell level. Herein we report a novel and reusable biomimetic micro-electrochemical sensor array with nitric oxide (NO) sensing-interface based on metalloporphyrin and 3-aminophenylboronic acid (APBA) co-functionalized reduced graphene oxide (rGO). The assembling of high specificity catalytic but semi-conductive metalloporphyrin with high electric conductive rGO confers the sensor with sub-nanomolar sensitivity. Further coupling with the small cell-adhesive molecule APBA obviously enhances the cytocompatibility of the microsensor without diminishing the sensitivity, while the reversible reactivity between APBA and cell membrane carbohydrates allows practical reusability. The microsensor was successfully used to sensitively monitor, in real-time, the release of NO molecules from human endothelial cells being cultured directly on the sensor. This demonstrates its potential application in the detection of NO with very low bioactive concentrations for the better understanding of its physiological function and for medical tracking of patient states.     

The pillar[5]arene-based spun thin films: preparation,characterization, development of optical and mass sensitive sensors for swelling dynamics and gas sensing abilities

Pillar[5]arene (P5)-based materials can be preferable one of the most sensing elements in chemical sensor applications due to their high cavity and their special chiral structure. While the P5-based macrocycle molecules have been utilized as thin-film materials, the reports of chemical sensor application by performing P5 as sensor molecules have been very limited in the available literature. In this report, quinoline P5 (P5-Q) molecules were used to produce thin films via spin coating technique. P5-Q spun films were characterized with Atomic Force Microscopy (AFM) and Ultraviolet–Visible (UV–Vis) spectrophotometer. The gas sensing abilities of these P5-Q spun films were investigated by Quartz Crystal Microbalance (QCM) and Surface Plasmon Resonance (SPR) techniques. In order to illuminate the gas sensing properties of P5-Q spun films, they were prepared as mass-sensitive and optical sensors. These sensors were utilized for its sensing abilities against organic vapours (acetone, methyl alcohol, and ethyl alcohol) by the mechanism of host–guest interaction. The current study also describes the diffusion coefficients of these organic vapors to illuminate the swelling dynamics of P5-Q spun films by performing Fick’s diffusion equation. The responses of P5-based optical (SPR) or mass sensitive (QCM) sensor in terms of the change in reflective intensity or the change in frequency and the values of diffusion coefficients showed that P5-Q molecules can be developed as potential chemical sensor element for acetone vapor compared to alcohol vapors.

     

Nanostructured Substrates for Optical Sensing

Sensors that change color have the advantages of versatility, ease of use, high sensitivity, and low cost. The recent development of optically based chemical sensing platforms has increasingly employed substrates manufactured with advanced processing or fabrication techniques to provide precise control over shape and morphology of the sensor micro- and nano-structure. New sensors have resulted with improved capabilities for a number of sensing applications, including the detection of biomolecules and environmental monitoring. This perspective focuses on recent optical sensor devices that utilize nanostructured substrates.     

Optical fluid and biomolecule transport with thermal fields

A long standing goal is the direct optical control of biomolecules and water for applications ranging from microfluidics over biomolecule detection to non-equilibrium biophysics. Thermal forces originating from optically applied, dynamic microscale temperature gradients have shown to possess great potential to reach this goal. It was demonstrated that laser heating by a few Kelvin can generate and guide water flow on the micrometre scale in bulk fluid, gel matrices or ice without requiring any lithographic structuring. Biomolecules on the other hand can be transported by thermal gradients, a mechanism termed thermophoresis, thermal diffusion or Soret effect. This molecule transport is the subject of current research, however it can be used to both characterize biomolecules and to record binding curves of important biological binding reactions, even in their native matrix of blood serum. Interestingly, thermophoresis can be easily combined with the optothermal fluid control. As a result, molecule traps can be created in a variety of geometries, enabling the trapping of small biomolecules, like for example very short DNA molecules. The combination with DNA replication from thermal convection allows us to approach molecular evolution with concurrent replication and selection processes inside a single chamber: replication is driven by thermal convection and selection by the concurrent accumulation of the DNA molecules. From the short but intense history of applying thermal fields to control fluid flow and biological molecules, we infer that many unexpected and highly synergistic effects and applications are likely to be explored in the future.     

Fibre optic chemical sensors based on evanescent wave interactions in sol-gel-derived porous coatings

A simple, low-cost technique for fabricating reagent-mediated fibre-optic chemical sensors (optrodes) is described and the performance of a range of such sensors is reported. The technique is based on coating an unclad portion of an optical fibre with a microporous glass film prepared by the sol-gel process. Although tip- and side-coating are both possible with this technique, the latter, which employs evanescent wave interactions, offers particular advantages in terms of sensor performance, control of sensitivity and quality of coating. The sol-gel-derived film is used to provide a robust support matrix in which analyte-sensitive dyes are entrapped and into which smaller analyte molecules may diffuse. The benefits of this sol-gel approach to sensor fabrication are illustrated by results from a range of sensors for pH, ammonia and oxygen based on both evanescent wave absorption and evanescent wave excitation of fluorescence.     

A Biomimetic Phosphatidylcholine‐Terminated Monolayer Greatly Improves the In Vivo Performance of Electrochemical Aptamer‐Based Sensors

The real‐time monitoring of specific analytes in situ in the living body would greatly advance our understanding of physiology and the development of personalized medicine. Because they are continuous (wash‐free and reagentless) and are able to work in complex media (e.g., undiluted serum), electrochemical aptamer‐based (E‐AB) sensors are promising candidates to fill this role. E‐AB sensors suffer, however, from often‐severe baseline drift when deployed in undiluted whole blood either in vitro or in vivo. We demonstrate that cell‐membrane‐mimicking phosphatidylcholine (PC)‐terminated monolayers improve the performance of E‐AB sensors, reducing the baseline drift from around 70 % to just a few percent after several hours in flowing whole blood in vitro. With this improvement comes the ability to deploy E‐AB sensors directly in situ in the veins of live animals, achieving micromolar precision over many hours without the use of physical barriers or active drift‐correction algorithms.     

Engineering of Nucleic Acids and Synthetic Cofactors as Holo Sensors for Probing Signaling Molecules in the Cellular Membrane Microenvironment

The comprehensive understanding of the mechanisms underlying the interaction of cells with their membrane microenvironment is of great value for fundamental biological research; however, tracking biomolecules on cell surfaces with high temporal and spatial resolution remains a challenge. Herein, a modular strategy is presented for the construction of cell surface DNA‐based sensors by engineering DNA motifs and synthetic cofactors. In this strategy, a stimuli‐reactive organic molecule is employed as the cofactor for the DNA motif, and the self‐assembly of them forms a FRET‐based holo DNA‐based sensor. With the use of the DNA‐based sensors, the versatility of this modular strategy has been demonstrated in the ratiometric imaging of the cellular extrusion process of endogenous signaling molecules, including sulfur dioxide derivatives and nitric oxide.     

Sampling of slow diffusive conformational transitions with accelerated molecular dynamics

Slow diffusive conformational transitions play key functional roles in biomolecular systems. Our ability to sample these motions with molecular dynamics simulation in explicit solvent is limited by the slow diffusion of the solvent molecules around the biomolecules. Previously, we proposed an accelerated molecular dynamics method that has been shown to efficiently sample the torsional degrees of freedom of biomolecules beyond the millisecond timescale. However, in our previous approach, large-amplitude displacements of biomolecules are still slowed by the diffusion of the solvent. Here we present a unified approach of efficiently sampling both the torsional degrees of freedom and the diffusive motions concurrently. We show that this approach samples the configuration space more efficiently than normal molecular dynamics and that ensemble averages converge faster to the correct values.     

Preparation and properties of plasma-initiated graft copolymerized membranes for blood plasma separation

A hydrophilic composite membrane for blood plasma separation has been prepared by surface graft copolymerization initiated by low-temperature plasma (LTP). After short LTP pre-irradiation onto a microporous polypropylene (PP) membrane, N-N-dimethylacrylamide (DMAA) vapor was introduced for grafting. The PP membrane had a 0.45 μm effective pore size and a 130 μm thickness. The rate of DMAA grafting onto PP was very high, even in vapor-solid phase reaction under reduced pressure; DMAA 1 mm Hg (133Pa). The percentage of grafted poly-DMAA (PDMAA) reached 15% within 5 min post graft polymerization, and the membrane surface, including the interior surface of pores, became completely hydrophilic. There was no apparent change observed in the membrane morphology in the dry state after the PDMAA-grafted layer was formed. However, water flux significantly decreased, probably due to swelling of the PDMAA-grafted layer. With a grafting yield below 17%, the PDMAA-grafted PP (PP-g-PDMAA) membrane showed a good separation capability of plasma from whole blood. The PP-g-PDMAA membrane exhibited low complement activating potential, high sieving coefficient for plasma proteins and high blood compatibility. Decreases in adsorption of blood cells, plasma proteins, and other biomolecules may be the reason for the membrane performance.     

A Green and Wide-Scope Approach for Chiroptical Sensing of Organic Molecules through Biomimetic Recognition in Water

Optical chirality sensing has attracted a lot of interest due to its potential in high-throughput screening in chirality analysis. A molecular sensor is required to convert the chirality of analytes into optical signals. Although many molecular sensors have been reported, sensors with wide substrate scope remain to be developed. Herein, we report that the amide naphthotube-based chirality sensors have an unprecedented wide scope for chiroptical sensing of organic molecules. The substrates include, but are not limited to common organic products in asymmetric catalysis, chiral molecules with inert groups or remote functional groups from their chiral centers, natural products and their derivatives, and chiral drugs. The effective chirality sensing is based on biomimetic recognition in water and on effective chirality transfer through guest-induced formation of a chiral conformation of the sensors. Furthermore, the sensors can be used in real-time monitoring on reaction kinetics in water and in determining absolute configurations and ee values of the products in asymmetric catalysis.     

基于石墨烯光子晶体光纤的流体传感器

与传统的传感器设备阵列相比,由于结构更为简单,具有广泛检测兼容性的光纤系统逐渐成为分布式监测的有力候选者。然而,受工作机制的限制,大多数光纤传感器仍局限于对折射率等物理参数进行探测,一种用于环境化学监测的全光纤分布式传感系统亟待研发。本工作中,我们向化学气相沉积法生长的石墨烯光子晶体光纤(Gr-PCF)中引入了一种化学传感机制。初步结果表明,石墨烯光子晶体光纤可以选择性地检测浓度为ppb级的二氧化氮气体,并在液体中表现出离子敏感性。石墨烯光子晶体光纤与光纤通信系统的波分、时分复用技术结合后,将为实现分布式光学传感环境问题提供巨大的潜力和机会。     

Aptamer sandwich-based carbon nanotube sensors for single-carbon-atomic-resolution detection of non-polar small molecular species

A portable sensor platform for the detection of small molecular species is crucial for the on-site monitoring of environmental pollutants, food toxicants, and disease-related metabolites. However, it is still extremely difficult to find highly selective and sensitive sensor platforms for general small molecular detection. Herein, we report aptamer sandwich-based carbon nanotube sensor strategy for small molecular detection, where aptamers were utilized to capture target molecules as well as to enhance the sensor signals. We successfully demonstrated the detection of non-polar bisphenol A molecules with a 1 pM sensitivity. Significantly, our sensors were able to distinguish between similar small molecular species with single-carbon-atomic resolution. Furthermore, using the additional biotin modification on labeling aptamer, we enhanced the detection limit of our sensors down to 10 fM. This strategy allowed us to detect non-polar small molecular species using carbon nanotube transistors, thus overcoming the fundamental limitation of field effect transistor-based sensors. Considering the extensive applications of sandwich assay for the detection of rather large biomolecules, our results should open up completely new dimension in small molecular detection technology and should enable a broad range of applications such as environmental protection and food safety.     

Amperometric monitoring of lactate accumulation in rabbit ischemic myocardium

Fabrication and characterization of miniature, flexible, planar biosensors for monitoring l-lactate accumulation in an ischemic myocardium are described. Three configurations of Au-based electrodes were fabricated by a photolithographic technique on flexible polyimide Kapton((R)) foil. All sensors are based on an immobilized lactate oxidase with amperometric detection of the enzymatically produced hydrogen peroxide at a platinum-electroplated-gold base electrode polarized at 0.5 V versus Ag/AgCl. An inner electropolymeric layer is used to prevent electrode fouling and to reject the interference effects of easily oxidizable molecules. In addition, a diffusion controlling outer layer that greatly enhances the linear dynamic range of the sensor, is obtained by casting a polyurethane external film. The developed sensor was evaluated in vitro and proved to have high selectivity, good operational stability, good accuracy and precision (average recovery = 102.3 +/- 0.4% for control sera), fast response time (t(95) = 20 s) and high upper limit of the linear dynamic range (25-80 mM, with sensitivity of 1.7-0.4 nA mM(-1) respectively at PO(2) = 15 mmHg). Subsequently, the sensor was brought into direct contact with the surface of the rabbit papillary muscle and used for continuous quantitative monitoring of extracellular lactate accumulation during no-flow ischemia.     

Glucose Biosensor Based on Oxygen Electrode Part III: Long-Term Performance of the Glucose Biosensor in Blood Plasma at Body Temperature

Abstract

A potentially implantable glucose biosensor for continuous monitoring of glucose levels in diabetic patients has been developed. The glucose biosensor is based on an amperometric oxygen electrode and Glucose Oxidase immobilized on carbon powder held in a form of a liquid suspension. The enzyme material can be replaced (the sensor recharged) without sensor disassembly. Glucose diffusion membranes from polycarbonate (PC) and from polytetrafluorethylene (PTFE) coated with silastic are used.

Sensors were evaluated continuously operating in phosphate buffer solution and in undiluted blood plasma at body temperature. Calibration curves of the sensors were periodically obtained. The sensors show stable performance during at least 1200 hours of operation without refilling of the enzyme. The PTFE membrane demonstrates high mechanical stability and is little effected by long-term operation in undiluted blood plasma.     

Universal Strategy for Improving the Sensitivity of Detecting Volatile Organic Compounds by Patterned Arrays

The diffusion of target analytes is a determining factor for the sensitivity of a given gas sensor. Surface adsorption results in a low‐concentration region near the sensor surface, producing a concentration gradient perpendicular to the surface, and drives a net flux of molecules toward solid reactive reagents on the sensor surface, that is, vertical diffusion. Here, organic semiconductor supramolecules were patterned into micromeshed arrays to integrate vertical and horizontal diffusion pathways. When used as a gas sensor, these arrays have an order of magnitude higher sensitivity than traditional film‐based sensors. The sensor sensitivity ramp down with the increase in coverage density of reactive reagents, yielding two linear regions demarcated by 0.3 coverage, which are identified by the experimental results and simulations. The universal nature of template‐assisted patterning allows adjustments in the composition, size, and shape of the constituent material, including nanofibers, nanoparticles, and molecules, and thus serves to improve the sensitivity of gas sensors for detecting various volatile organic compounds.     

Optical Chemical Hydrazine Sensor from Hybrid Organic-Inorganic Materials

Original hybrid organic-inorganic materials have been synthesised, characterised and used as optical chemical hydrazine sensors. Because of its optical and chemical properties, 4-(dimethyl)aminobenzaldehyde (DMAB) was chosen as indicator. DMAB has been immobilised by physical entrapment in a microporous silica network or by a chemical bonding on a colloidal silica network. The response time of the sensor was essentially governed by the diffusion of hydrazine in the host matrix whereas its life time was dependent on the retention of DMAB. These two features were controlled by the nature and the quantity of the network agent and the catalyst, by the ageing time of the sol, and the drying and thermal treatment of the films.     

Zeolite-fiber integrated optical chemical sensors for detection of dissolved organics in water

MFI zeolite coated optical fiber sensors have been developed for in situ detection of dissolved organics in water. The sensors operate by monitoring the optical reflectivity changes caused by the selective adsorption of organic molecules, i.e., 2-propanol or pentanoic acid in this study, from aqueous solutions in the zeolitic pores. Reversible and monotonic sensor signals were observed in response to the variation of 2-propanol concentration in water with fast response. However, the sensor exhibited a much slower response to pentanoic acid than to 2-propanol. It was also found that substitution of Si by Al in the MFI framework increased the adsorption of pentanoic acid that resulted in enhanced sensor responses.