Development of microbiosensors

Semiconductor fabrication technology was used for development of ion sensitive field effect transistor (ISFET) and micro-electrodes which have been utilized as transducers of enzyme-based microbiosensors. A urea sensor consisted of two ISFETs; one ISFET is urease-coated ISFET and the other ISFET is reference ISFET. A linear relationship was obtained between the initial rate of voltage change and the logarithm of urea concentration over the range 1.3 to 16.7 mM. ATP and hypoxanthine sensors were also developed utilizing ISFET as a transducer. Furthermore, microelectrodes such as hydrogen peroxide and oxygen sensors were prepared by the silicone fabrication technology. A glucose sensor consisted of a hydrogen peroxide electrode and immobilized glucose oxidase membrane. A linear relationship was observed between the current increase and the concentration of glucose (1–100 mg dl⁻¹). A microoxygen electrode was constructed from Au electrodes, polymer matrix containing alkaline electrolyte and a photocross-linkable polymer membrane. This electrode was used as a transducer in microglucose sensor. A microglutamic acid sensor is also described.     

Alcohol-FET sensor based on a complex cell membrane enzyme system

An alcohol -FET sensor was developed by use of a complex enzyme system in a cell membrane and an ion-sensitive field effect transistor (ISFET). The cell membrane of Gluconobacter suboxydans IFO 12528, which converts ethanol to acetic acid, was immobilized on the gate of an ISFET with calcium alginate gel coated with nitrocellulose. This ISFET (1), a reference ISFET without the cell membrane (ISFET 2) and an Ag/AgCl reference electrode were placed in 5 mM Trismalate buffer (pH 5.5, 25°C), and the differential output between ISFETS 1 and 2 was measured. The output of the sensor was stabilized by adding pyrroloquinoline quinone. The response time was ca. 10 min., and there was a linear relationship between the differential output voltage and the ethanol concentration up to 20 mg l^?1. The output of the sensor was stable for 40 h below 30°C. The sensor responded to ethanol, propan- 1-ol and butan- 1-ol, but not to methanol, propan-2-ol and butan-2-ol. The sensor was used to determine blood ethanol.     

Molecular engineering of conjugated polymers for solar cells and field‐effect transistors: Side‐chain versus main‐chain electron acceptors

Two model polymers, containing fluorene as an electron‐donating moiety and benzothiadiazole (BT) as an electron‐accepting moiety, have been synthesized by Suzuki coupling reaction. Both polymers are composed of the same chemical composition, but the BT acceptor can be either at a side‐chain (i.e., S‐polymer) or along the polymer main chain (i.e., M‐polymer). Their optical, electrochemical, and photovoltaic properties, together with the field‐effect transistor (FET) characteristics, have been investigated experimentally and theoretically. The FET carrier mobilities were estimated to be 5.20 × 10^?5 and 3.12 × 10^?4 cm² V^?1 s^?1 for the S‐polymer and M‐polymer, respectively. Furthermore, polymeric solar cells (PSCs) with the ITO/PEDOT:PSS/S‐polymer or M‐polymer:PC₇₁BM(1:4)/Al structure were constructed and demonstrated to show a power conversion efficiency of 0.82 and 1.24% for the S‐polymer and M‐polymer, respectively. The observed superior device performances for the M‐polymer in both FET and PSCs are attributable to its relatively low band‐gap and close molecular packing for efficient solar light harvesting and charge transport. This study provides important insights into the design of ideal structure–property relationships for conjugate polymers in FETs and PSCs. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Wearable Multiparameter Platform Based on AlGaN/GaN High‐electron‐mobility Transistors for Real‐time Monitoring of pH and Potassium Ions in Sweat

Biosensors based on field‐effect transistor (FET) structures have attracted considerable attention because they offer rapid, inexpensive parallel sensing and ultrasensitive label‐free detection. However, long‐term repeatable detection cannot be performed, and Ag/AgCl reference electrode design is complicated, which has hindered FET biosensors from becoming truly wearable health‐monitoring platforms. In this paper, we propose a novel wearable detection platform based on AlGaN/GaN high‐electron‐mobility transistors (HEMTs). In this platform, a sweatband was used to continuously collect sweat, and a pH detecting unit and a potassium ion detecting unit were formed by modifying different sensitive films to realize the long‐term stable and repeatable detection of pH and potassium ions. Experimental data show that the wearable detection platform based on AlGaN/GaN HEMTs has good sensitivity (pH 3–7 sensitivity is 45.72 μA/pH; pH 7.4–9 sensitivity is 51.073 μA/pH; and K⁺ sensitivity is 4.94 μA/lgα_K⁺), stability (28 days) and repeatability (the relative standard deviation (RSD) of pH 3–7 sensitivity is 2.6 %, the RSD of pH 7.4–9 sensitivity is 2.1 %, and the RSD of K⁺ sensitivity is 7.3 %). Our newly proposed wearable platform has excellent potential for predictive analytics and personalized medical treatment.     

Low‐Voltage All‐Polymer Field‐Effect Transistor Fabricated Using an Inkjet Printing Technique

Summary: An all‐polymer field‐effect transistor (FET) fabricated using an inkjet printing technique is presented in this paper. Poly(3,4‐ethylenedioxythiophene) works as the source/drain/gate electrode material because of its good conductivity. Polypyrrole acts as the semiconducting layer. Poly(vinyl pyrrolidone) K60, an insulating polymer with a dielectric constant of 60, operates as the dielectric layer. All the polymers are diluted with deionized water, and can be printed with a piezoelectric inkjet printing system. The device functions at a depletion mode with low operation voltage. It has a field‐effect mobility of 0.1 cm² · V⁻¹ · s⁻¹, an on/off ratio of 2.9 × 10³, and a subthreshold slope of 2.81 V · decade⁻¹.

Schematic of the all‐polymer FET synthesized here.     

Micro Ammonia Sensor

Abstract

A micro ammonia sensor, consisting of an ISFET covered with a dry membrane which is made from nonactin and substituted poly-γ-methyl-L-glutamate (PMG) is described. The gate output voltage of the micro ammonia sensor increased with NH₄OH addition. The response time of the sensor was 2 min at 30°C, and the sensor exhibited superior selectivity for NH₄ ⁺ compared to a pH sensitive ISFET.     

Parylene-gate isfet and chemical modification of its surface with crown ether compounds

A hydrophobic polymer such as parylene has ion dissociation sites of extremely low density. An electrolyte-parylene interface manifests a constant potential independent of solution composition. The parylene-gate ISFET can be used as a solid state reference electrode. These films can also be used for the substrate of a CHEMFET, where the recent chemical modification technology is introduced. In this paper, the concept of a parylene-gate ISFET based on the site-binding model is investigated. As applications, a probe-type all solid state pH sensor integrating an Si₃N₄ gate, a parylene gate and an Au pseudo-reference electrode is discussed. A pK ISFET chemically modified with crown ether compounds is also reported.     

Detecting Both Physical and (Bio‐)Chemical Parameters by Means of ISFET Devices

A multi‐parameter sensor system for the detection of eight (bio‐)chemical and physical parameters (pH, potassium concentration, penicillin concentration, diffusion coefficient of H⁺‐ and OH ^–‐ions, temperature, flow velocity, flow direction and liquid level) is realized by using the same transducer principle. A Ta₂O₅‐gate ISFET (ion‐sensitive field‐effect transistor) is applied as basic transducer for all kinds of sensors. The multi‐parameter detection is achieved by means of sequentially or simultaneously scheduling of the hybride sensor modules consisting of four ISFET structures and an ion generator in different sensor arrangements and/or different operation modes. Thus, more parameters (eight) can be detected than the number of sensors (four) in the system.     

Borazon-gate pH-sensitive field effect transistor

A borazon-gate ISFET is used as a pH sensor. Boron nitride was deposited by the reactive-pulse plasma method and electron diffraction served for membrane identification. The borazon-gate sensors responded linearly to pH in the range 1.8–10; the slope was about 52 mV pH^?1. Selectivity for H⁺ ions over K⁺, Na⁺ or Ca²⁺ ions was better than that of silicon nitride-gate ISFETs.     

Reducing the interference from CO2 or organic acids in ion-selective polymer membrane sensors having a field-effect transistor as internal reference element

Changes in sample concentrations of CO₂ or organic acids cause potential instabilities when polymer membranes are directly applied to the surface of ion-selective field-effect transistors (ISFETs). Currently used designs avoid this well-documented effect by placing a layer of aqueous buffer between polymeric membrane and ISFET serving as internal reference element. Here, we propose another solution to the problem. In order to compensate for the effect of pH changes on the ISFET threshold voltage, a double membrane is applied whose inner layer is pH-sensitive, while the outer layer exposed to the sample is a conventional ion-selective membrane. It is shown that this approach strongly reduces the earlier-mentioned interference effects.     

Characteristics of the hydrogen ion-sensitive field effect transistors with sol-gel-derived lead titanate gate

The sol-gel-derived lead titanate (PbTiO₃) membrane has been successfully applied as a pH sensitive layer to form the PbTiO₃ gate ion-sensitive field-effect transistor (ISFET). There exhibit the excellent quasi-Nernstian response of 56-59 mV pH⁻¹, good surface adsorption and anticorrosion characteristics via the C-V measurement of the EIS structure. At a specific pH concentration, the output and transfer characteristics are very similar to the behaviours of MOSFETs, and the ISFET model can be derived by the modified MOSFET model. As it operated in the nonsaturation region, there exhibits a linear pH response of about 56-59 mV pH⁻¹. On the other hand, as it operated in the saturation region, the pH response and linearity can be controlled by adjusting the V_GS values, e.g. the pH responses of −4.2, −24.8 and −31.3 μA pH⁻¹ and the correlation coefficients of 0.9491, 0.9995 and 0.9996 at V_GS=1, 3 and 5 V can be obtained, respectively. Besides, in order to get the best pH response and the minimized leakage current, the heat treatment temperature of the PbTiO₃ membrane must be limited between 350 and 450 °C.     

Synthesis and characterization of a Eu-containing polymer precursor featuring thenoyltrifluoroacetone and 5-acrylamido-1,10-phenanthroline

A polymerizable ligand, 5-acrylamido-1,10-phenanthroline (L), was synthesized. Its Eu(III) complex with 2-thenoyltrifluoroacetone (HTTA) was prepared and characterized by elemental analysis, IR, MS, and ¹H NMR spectra. The photophysical properties of the complex were studied in detail by using UV, luminescence spectra, luminescence lifetime and quantum yield. The complex shows a remarkable luminescence quantum yield at room temperature (40.1%) upon ligand excitation and a long ⁵D₀ lifetime (590 μs), which makes it not only a promising light-conversion molecular device but also an excellent luminescent polymer precursor.     

A novel Urushi matrix chloride ion-selective field effect transistor

A durable chloride ion-selective field effect transistor (ISFET) is proposed with Urushi as the membrane matrix. The chloride ion-sensing material is a quaternary ammonium chloride: trioctylmethylammonium chloride (TOMA-Cl) or tridodecylmethylammonium chloride (TDMA-Cl). The optimum composition of the Urushi membrane was found by use of Urushi ion-selective electrodes. The mixture with the most favourable composition was coated on the gate region of the FET device. The Urushi ISFET with TDMA-Cl proved to be superior to that with TOMA-Cl, in sensitivity, linearity and selectivity. The Urushi ISFET with TDMA-Cl showed a linear response of about -51 mV per decade change of chloride ion activity in the range 10(-4)-1M. The Urushi ISFET showed excellent stability and durability for over two months, because of strong adhesion of the membrane to the Si(3)N(4) gate.     

Polyelectrolyte effects on the quenching of pyrene fluorescence in solutions of a pyrene substituted poly(acrylic acid)

The quenching of pyrene fluorescence by nitromethane, Tl⁺, Cu²⁺, I^?, and 4-dimethylaminopyridine (DMAP) in aqueous solutions of a pyrene substituted poly(acrylic acid) ( 1 ) was influenced by the “polyelectrolyte effect” of 1 . The efficiency of quenching in solutions of 1 was measured in terms of the Stern–Volmer constants for dynamic and static quenching which were obtained from comparison of the intensity and lifetime of pyrene fluorescence in solutions of 1 and a monomer model compound. The efficiency of quenching in solutions of 1 was always greater at high pH ( 9 ) in comparison to that at low pH ( 4 ). The ionization of carboxylic groups in 1 caused an expansion of the polymer mainchain and concomitant exposure of the pyrene molecules to the aqueous phase and quencher. The polyanion domain of 1 favored the condensation of cationic quenchers and could account for very efficient quenching in case of Cu²⁺ and Tl⁺. A very efficient quenching of pyrene fluorescence in solutions of 1 by DMAP at high pH was attributed to the hydrophobic interactions of DMAP and pyrene moiety. The iodide ions were less efficient quenchers of pyrene fluorescence due to electrostatic repulsion from the polyanion. The efficiency of quenching by nitromethane was not significantly affected by ionization of the carboxylic groups in 1 .     

Preparation of Selenoinsulin as a Long‐Lasting Insulin Analogue

Synthetic insulin analogues with a long lifetime are current drug targets for the therapy of diabetic patients. The replacement of the interchain disulfide with a diselenide bridge, which is more resistant to reduction and internal bond rotation, can enhance the lifetime of insulin in the presence of the insulin‐degrading enzyme (IDE) without impairing the hormonal function. The [C7U^A,C7U^B] variant of bovine pancreatic insulin (BPIns) was successfully prepared by using two selenocysteine peptides (i.e., the C7U analogues of A‐ and B‐chains, respectively). In a buffer solution at pH 10 they spontaneously assembled under thermodynamic control to the correct insulin fold. The selenoinsulin (Se‐Ins) exhibited a bioactivity comparable to that of BPIns. Interestingly, degradation of Se‐Ins with IDE was significantly decelerated (τ _1/2≈8 h vs. ≈1 h for BPIns). The lifetime enhancement could be due to both the intrinsic stability of the diselenide bond and local conformational changes induced by the substitution.     

Chromium(III) Ion Selective Electrode Based on Oxalic Acid Bis(Cyclohexylidene Hydrazide)

A poly(vinyl chloride) membrane sensor based on oxalic acid bis (cyclohexylidene hydrazide) as membrane carrier was prepared and investigated as a Cr(III)‐selective electrode. The electrode reveals a Nernstian behavior (slope 19.8±0.4 mV decade^?1) over a wide Cr(III) ion concentration range 1.0×10^?7–1.0×10^?2 mol dm^?3 with a very low limit of detection (i.e., down to 6.3×10^?8 mol dm^?3). The potentiometric response of the sensor is independent of the pH of the test solution in the pH range 1.7–6.5. The electrode possesses advantage of very fast response, relatively long lifetime and especially good selectivity to wide variety of other cations. The sensor was used as an indicator electrode, in the potentiometric titration of chromium ion and in the determination of Cr(III) in waste water and alloy samples.     

Preparation of Selenoinsulin as a Long-Lasting Insulin Analogue

Synthetic insulin analogues with a long lifetime are current drug targets for the therapy of diabetic patients. The replacement of the interchain disulfide with a diselenide bridge, which is more resistant to reduction and internal bond rotation, can enhance the lifetime of insulin in the presence of the insulin-degrading enzyme (IDE) without impairing the hormonal function. The [C7U^A,C7U^B] variant of bovine pancreatic insulin (BPIns) was successfully prepared by using two selenocysteine peptides (i.e., the C7U analogues of A- and B-chains, respectively). In a buffer solution at pH 10 they spontaneously assembled under thermodynamic control to the correct insulin fold. The selenoinsulin (Se-Ins) exhibited a bioactivity comparable to that of BPIns. Interestingly, degradation of Se-Ins with IDE was significantly decelerated (τ_1/2≈8 h vs. ≈1 h for BPIns). The lifetime enhancement could be due to both the intrinsic stability of the diselenide bond and local conformational changes induced by the substitution.     

Synthesis of <Emphasis Type="Italic">O</Emphasis>-(2-[<Superscript>18</Superscript>F]fluoroethyl)-<Emphasis Type="Italic">L</Emphasis>-tyrosine and its biological evaluation in B16 melanoma-bearing mice as PET tracer for tumor imaging

O-(2-[¹⁸F]fluoroethyl)-L-tyrosine ([¹⁸F]FET), a fluorine-18 labeled analogue of tyrosine, has been synthesized and biologically evaluated in tumor-bearing mice. The whole synthesis procedure is completed within 50 min. The radiochemical yield is about 40% (no decay corrected) and radiochemical purity more than 97% after simplified solid phase extraction. [¹⁸F]FET shows rapid, high uptake and long retention in the tumor as well as low uptake in the brain. The ratios of tumor-to-muscle (T/M) and tumor-to-blood (T/B) of [¹⁸F]FET are similar to those of [¹⁸F]FDG, but the ratios of tumor-to-brain (T/Br) are 2–3 times higher than that of [¹⁸F]FDG. Autoradiography of [¹⁸F]FET demonstrates a remarkable accumulation in melanoma with high contrast. It appears to be a probable competitive candidate for melanoma imaging with PET. Supported by the Knowledge Innovation Project of Chinese Academy of Sciences (No. KJCX1-SW-08) and the National Natural Science Foundation of China (Grant No. 30371634)