Comparison of Planar and 3‐D Interdigitated Electrodes as Electrochemical Impedance Biosensors

It has been reported that the introduction of a dielectric barrier between adjacent digits of an interdigitated electrode array can improve the sensitivity of the array as an electrochemical impedance biosensor. Here we present an in‐depth analysis of the impedance in planar interdigitated electrodes and 3‐D interdigitated electrodes (with dielectric barriers). The analysis indicates that the planar geometry not only provides lower impedance but also a higher change impedance as a result of molecular immobilization on the electrode array surface.     

Sol–Gel‐Derived Biohybrid Materials Incorporating Long‐Chain DNA Aptamers

Sol–gel‐derived bio/inorganic hybrid materials have been examined for diverse applications, including biosensing, affinity chromatography and drug discovery. However, such materials have mostly been restricted to the interaction between entrapped biorecognition elements and small molecules, owing to the requirement for nanometer‐scale mesopores in the matrix to retain entrapped biorecognition elements. Herein, we report on a new class of macroporous bio/inorganic hybrids, engineered through a high‐throughput materials screening approach, that entrap micron‐sized concatemeric DNA aptamers. We demonstrate that the entrapment of these long‐chain DNA aptamers allows their retention within the macropores of the silica material, so that aptamers can interact with high molecular weight targets such as proteins. Our approach overcomes the major limitation of previous sol–gel‐derived biohybrid materials by enabling molecular recognition for targets beyond small molecules.     

Aptamer‐Based SERS Assay of ATP and Lysozyme by Using Primer Self‐Generation

A simple bifunctional surface‐enhanced Raman scattering (SERS) assay based on primer self‐generation strand‐displacement polymerization (PS‐SDP) is developed to detect small molecules or proteins in parallel. Triphosphate (ATP) and lysozyme are used as the models of small molecules and proteins. Compared to traditional bifunctional methods, the method possesses some remarkable features as follows: 1) by virtue of the simple PS‐SDP reaction, a bifunctional aptamer assembly binding of trigger 1 and trigger 2 was used as a functional structure for the simultaneous sensing of ATP or lysozyme. 2) The concept of isothermal amplification bifunctional detection has been first introduced into SERS biosensing applications as a signal‐amplification tool. 3) The problem of high background induced by excess bio‐barcodes is circumvented by using magnetic beads (MBs) as the carrier of signal‐output products and massive of hairpin DNA binding with SERS active bio‐barcodes relied on Au nanoparticles (Au NPs), SERS signal is significantly enhanced. Overall, with multiple amplification steps and one magnetic‐separation procedure, this flexible biosensing system exhibited not only high sensitivity and specificity, with the detection limits of ATP and lysozyme of 0.05 nM and 10 fM , respectively.     

DNA‐Mediated Proximity‐Based Assembly Circuit for Actuation of Biochemical Reactions

Smart nanodevices that integrate molecular recognition and signal production hold great promise for the point‐of‐care (POC) diagnostic applications. Herein, the development of a DNA‐mediated proximity assembly of biochemical reactions, which was capable of sensing various bio‐targets and reporting easy‐to‐read signals is reported. The circuit was composed of a DNA hairpin‐locked catalytic cofactor with inhibited activity. Specific molecular inputs can trigger a conformational switch of the DNA locks through the mechanisms of toehold displacement and aptamer switching, exposing an active cofactor. The subsequent assembly of an enzyme/cofactor pair actuated a reaction to produce colorimetric or fluorescence signals for detecting target molecules. The developed system could be potentially applied to smart biosensing in molecular diagnostics and POC tests.     

Impedimetric Aptasensor for Thrombin Recognition Based on CD Support

We report an aptamer biosensing array for thrombin detection by measuring the electrochemical impedance upon aptamer‐protein formation at the surface of CD‐trodes (GCDTs) in the presence of the redox couple [Fe(CN)₆]^3?/4?. GCDTs are fabricated from recordable compact discs that contain a fine gold layer. The biosensor is constructed by self‐assembling of a thiol‐modified thrombin binding aptamer (TBA) onto a GCDT surface. The sensor reveals good ligand specificity, recognition in a wide range of thrombin concentrations from 20 nM to 1 µM with a limit of detection of 5 nM.     

Nickel Hydroxide Nanoparticles on Screen‐printed Electrodes as an Impedimetric Non‐enzymatic Glucose Sensor

In this study, the electrodeposition of nickel hydroxide nanoparticles onto a screen‐printed electrode (Ni(OH)₂/SPE) is described. Ni(OH)₂/SPE is proposed as an alternative non‐enzymatic glucose sensor based on Electrochemical Impedance Spectroscopy (EIS) measurements.The SPEs were modified by the cathodic electrodeposition of nickel, from a solution containing 0.010 M Ni(NO₃)₂ and 1 M NH₄Cl, at −1.3 V for 60 seconds. The SEM images show a uniform distribution of nickel spherical nanoparticles, with 60 nm average particle size. However, such morphology is not observed when the electrodeposition occurs in the absence of NH₄Cl. The electrochemical properties of the sensor were carefully evaluated by Cyclic Voltammetry. Ni(OH)₂/SPE shows a remarkable electrocatalytic behavior towards the oxidation of glucose in 0.1 M KOH. EIS measurements were carried out for Ni(OH)₂/SPE and a single‐frequency impedance method is proposed as transduction principle for glucose determination. The analysis of each parameter of complex impedance was performed. The best linear response was obtained for the module of impedance (|Z|) in the range of 0–2 mM of glucose at 0.1 Hz (R²=0.992) with a slope of 0.137 KΩ⁻¹⋅mM⁻¹ of glucose. Finally, Ni(OH)₂/SPE was utilized for quantification of glucose in blood samples.     

Nano‐Graphene Oxide Based Multichannel Sensor Arrays towards Sensing of Protein Mixtures

Optical array‐based sensors are attractive candidates for the detection of various bio‐analytes due to their convenient fabrication and measurements. For array‐based sensors, multichannel arrays are more advantageous and used frequently in many electronic sensors. But most reported optically array based sensors are constructed on a single channel array. This difficulty is mainly instigated from the overlap in optical responses. In this report we have used nano‐graphene oxide (nGO) and suitable fluorophores as sensor elements to construct a multichannel sensor array for the detection of protein analytes. By using the optimized multichannel array we are able to detect different proteins and mixtures of proteins with 100 % classification accuracy at sub‐nanomolar concentration. This modified method expedites the sensing analysis as well as minimizes the use of both analyte and sensor elements in array‐based protein sensing. We have also used this system for the single channel array‐based sensing to compare the sensitivity and the efficacy of these two systems for other applications. This work demonstrated an intrinsic trade‐off associated with these two methods which may be necessary to balance for array‐based analyte detections.     

Recent Advances on Electrochemical Biosensing Strategies toward Universal Point‐of‐Care Systems

A number of very recently developed electrochemical biosensing strategies are promoting electrochemical biosensing systems into practical point‐of‐care applications. The focus of research endeavors has transferred from detection of a specific analyte to the development of general biosensing strategies that can be applied for a single category of analytes, such as nucleic acids, proteins, and cells. In this Minireview, recent cutting‐edge research on electrochemical biosensing strategies are described. These developments resolved critical challenges regarding the application of electrochemical biosensors to practical point‐of‐care systems, such as rapid readout, simple biosensor fabrication method, ultra‐high detection sensitivity, direct analysis in a complex biological matrix, and multiplexed target analysis. This Minireview provides general guidelines both for scientists in the biosensing research community and for the biosensor industry on development of point‐of‐care system, benefiting global healthcare.     

Label-free electrical discrimination of cells at normal, apoptotic and necrotic status with a microfluidic device

As a label-free alternative of conventional flow cytometry, chip-based impedance measurement for single cell analysis has attracted increasing attentions in recent years. In this paper, we designed a T-shape microchannel and fabricated a pair of gold electrodes located horizontally on each side of the microchannel using a transfer printing method. Instant electric signals of flowing-through single cells were then detected by connecting the electrodes to a Keithley resistance and capacitance measurement system. Experimental results based on the simultaneous measurement of resistance and capacitance demonstrated that HL-60 and SMMC-7721 cells could be differentiated effectively. Moreover, SMMC-7721 cells at normal, apoptotic and necrotic status can also be discriminated in the flow. We discussed the possible mechanism for the discrimination of cell size and cell status by electrical analysis, and it is believed that the improvement of detection with our design results from more uniform distribution of the electric field. This microfluidic design may potentially become a promising approach for the label-free cell sorting and screening.     

Performance Assessment of a Perfluorosulfonic Acid‐type Membrane (i. e. Nafion™ 115) for an Enzymatic Fuel Cell

A high power enzymatic fuel‐cell was anticipated by using a recently developed glucose oxidase (GOx) immobilized bio‐anode, a conventional platinum?carbon based cathode and a popular high performance 125 μ‐thick perfluorosulfonic acid‐type proton exchange membrane (i. e. Nafion® 115). Unexpected current density decay from 2.13 mA cm^?2 to 0.28 mA cm^?2 was observed within 2 hours. Polarization measurements and AC impedance analysis indicated that loss of performance was linked to the membrane behavior. Ion exchange between buffer solution and membrane was perceived as the main cause for the fast performance loss. Saturation of the membrane with the cation in the buffer solution diminished proton transfer needed for cathode reaction. Charge transfer resistances, obtained from AC impedance data, increased with time substantially due to cation exchange within membrane. Replacement of membrane with the same enzyme electrode and cathode has resulted 100 % current density recovery on the fuel cell performance. It was concluded that a membrane, not affected by the buffer cations, was required for successful enzymatic fuel cell applications.     

Close‐Packed Two‐Dimensional Silver Nanoparticle Arrays: Quadrupolar and Dipolar Surface Plasmon Resonance Coupling

Silver nanoparticles (NPs) ranging in size from 40 to 100 nm were prepared in high yield by using an improved seed‐mediated method. The homogeneous Ag NPs were used as building blocks for 2D assembled Ag NP arrays by using an oil/water interface. A close‐packed 2D array of Ag NPs was fabricated by using packing molecules (3‐mercaptopropyltrimethoxysilane) to control the interparticle spacing. The homogeneous 2D Ag NP array exhibited a strong quadrupolar cooperative plasmon mode resonance and a dipolar red‐shift relative to individual Ag NPs suspended in solution. A well‐arranged 2D Ag NP array was embedded in polydimethylsiloxane film and, with biaxial stretching to control the interparticle distance, concomitant variations of the quadrupolar and dipolar couplings were observed. As the interparticle distance increased, the intensity of the quadrupolar cooperative plasmon mode resonance decreased and dipolar coupling completely disappeared. The local electric field of the 2D Ag NP array was calculated by using finite difference time domain simulation and qualitatively showed agreement with the experimental measurements.     

An Electrochemical Transducer Based on a Pentacene Double‐Gate Thin‐Film Transistor

We report an electrochemical transducer based on an organic double‐gate transistor. The bottom‐gate is given by a p‐doped silicon substrate, which is covered by 300 nm thermal oxide. A 20 nm pentacene film acts as the semiconducting layer, and a 50 nm tetratetracontane (TTC) alkane film is used as a top‐gate dielectric. An aqueous ionic solution acts as top‐gate. We record the transistor transfer characteristics by variation of the electrolyte potential via a Ag/AgCl electrode for various bottom‐gate settings. A change of the electrolyte potential results in a change of the transistor current and the characteristic behaviour of the device is in good agreement with the expected behaviour of a double‐gate transistor. The top‐gate capacitance of the alkane layer is as high as 2.6×10^?8 F cm^?2 determined by impedance measurements, indicating that TTC is a good choice as an organic top‐gate dielectric. The suitability of this transducer configuration for sensing in aqueous media is demonstrated by the detection of hexanoic acid and stearic acid molecules adsorbing to the alkane interface, respectively. We show that the transducer easily achieves a concentration sensitivity in the range of 100 nM.     

Sensitive Detection of Small Molecule–Protein Interactions on a Metal–Insulator–Metal Label‐Free Biosensing Platform

The need to develop label‐free biosensing devices that enable rapid analyses of interactions between small molecules/peptides and proteins for post‐genomic studies has increased significantly. We report a simple metal–insulator–metal (MIM) geometry for fabricating a highly sensitive detection platform for biosensing. MIM substrates consisting of an Au–PMMA–Ag nanolayer were extensively studied using both theoretical and experimental approaches. By monitoring reflectivity changes at the normal incidence angle, we observed molecular interactions as the thickness of the biolayer increased on the substrate surface. These interactions included the adsorption of various proteins (Mw=6–150 kD) and interactions between small molecules (Mw≤2 kD) and the immobilized proteins. The interaction of designed monosaccharide‐modified designed peptides with various lectins was also clearly detected. These interactions could not be detected by the conventional Au‐only substrate. Thus, the MIM approach affords a powerful label‐free biosensing device that will aid our understanding of protein interactions and recognition.     

Amplified DNA Detection Sensitivity Using Streptavidin－Biotinylated Protein Complex： Characterization by Electrochemical Impedance Spectroscopy

Thioi-terminated oligonucleotide was immobilized to gold sur-face by self-assembly method. A novel amplification strategy was introduced for improving the sensitivity of DNA hybridiza-tion using biotin labeled protein-streptavidin network complex. This complex can be formed in a cross-linking network of molecules so that the amplification of the response signal will be realized due to the big molecular size of the complex. It could be proved from the impedance technique that this amplification strategy caused dramatic improvement of the detection sensitivi-ty. These results give significant advances in the generality and sensitivity as it is applied to biosensing.     

Amplified Self‐Immolative Release of Small Molecules by Spatial Isolation of Reactive Groups on DNA‐Minimal Architectures

Triggering the release of small molecules in response to unique biomarkers is important for applications in drug delivery and biodetection. Due to low quantities of biomarker, amplifying release is necessary to gain appreciable responses. Nucleic acids have been used for both their biomarker‐recognition properties and as stimuli, notably in amplified small‐molecule release by nucleic‐acid‐templated catalysis (NATC). The multiple components and reversibility of NATC, however, make it difficult to apply in vivo. Herein, we report the use of the hybridization chain reaction (HCR) for the amplified, conditional release of small molecules from standalone nanodevices. We couple HCR with a DNA‐templated reaction resulting in the amplified, immolative release of small molecules. We integrate the HCR components into single nanodevices as DNA tracks and spherical nucleic acids, spatially isolating reactive groups until triggering. This could be applied to biosensing, imaging, and drug delivery.     

Advances in Metal‐Free Heterocycle‐Based Columnar Liquid Crystals

Liquid crystals are ordered soft materials formed by self‐organized molecules and can potentially be used as new functional materials for electron‐, ion‐ or molecular‐transport; optical; and bio‐active materials. In particular, the columnar liquid crystals are promising candidates used in various optical and electronic devices. For this purpose, design and synthesis of unconventional materials are essential. In this review, we have summarized several approaches for the synthesis of columnar liquid crystals composed of various heterocyclic systems. We also outline their liquid crystalline and other relevant properties, and their suitability for applications in diverse fields.     

电化学交流阻抗技术表征自组装多层膜

采用电化交流阻抗技术对一种新型电极表面修饰的自组装多层膜进行表征,通过阻抗谱分析,得出电荷传递电阻和双电层电容与膜层数的关系,证明该多层膜随数增加具有均匀增长,结构致密等特性.     

Single Conducting Polymer Nanowire Based Sequence‐Specific,Base‐Pair‐Length Dependant Label‐free DNA Sensor

We have fabricated a highly sensitive, simple and label‐free single polypyrrole (Ppy) nanowire based conductometric/chemiresistive DNA sensor. The fabrication was optimized in terms of probe DNA sequence immobilization using a linker molecule and using gold‐thiol interaction. Two resultant sensor designs working on two different sensing mechanisms (gating effect and work function based sensors) were tested to establish reliable sensor architecture with higher sensitivity and device‐to‐device reproducibility. The utility of the work function based configuration was demonstrated by detecting 19 base pair (bp) long breast cancer gene sequence with single nucleotide polymorphism (SNP) discrimination with high sensitivity, lower detection limit of ∼10⁻¹⁶ M and wide dynamic range (∼10⁻¹⁶ to 10⁻¹¹ M) in a small sample volume (30 µL). To further demonstrate the utility of the DNA sensor for detection of target sequences with different number of bases, targets with 21 and 36 bases were detected. These sequences have implications in environmental sample analysis or metagenomics. Sensor response showed increase with the number of bases in the target sequence. For long sequence (with 36 bases), effect of DNA alignment on sensor performance was studied.     

Capacitance Polypyrrole‐based Impedimetric Immunosensor for Interleukin‐10 Cytokine Detection

In the present study, we developed a novel label‐free capacitance impedimetric immunosensor based on the immobilization of the human monoclonal antibody anti‐interleukin‐10 (anti‐IL‐10 mAb) onto polypyrrole (PPy)‐modified silicon nitride (Si₃N₄) substrates. The immunosensor was used for the detection of the recombinant interleukin‐10 antigen (rh IL‐10) that may be secreted in patients at the early stage of inflammation. The immunosensor was created by chemical deposition of PPy conducting layer on pyrrole?silane (SPy)‐treated Si/SiO₂/Si₃N₄ substrates (Si/SiO₂/Si₃N₄?SPy), followed by anti‐IL‐10 mAb immobilization through carboxyl‐functionalized diazonium (CMA) protocol and carbodiimide chemistry. The surface characterization and the biofunctionalization steps were characterized by SEM, FTIR and cyclic voltammetry (CV) while the detection process was carried out by using electrochemical impedance spectroscopy (EIS) analyses. The created immunosensor showed two linear fittings (R²=0.999) for the detection of rh IL‐10 within the concentration range from 1–50 pg/mL. It exhibited high sensitivity (0.1128 (pg/mL)^?1) with a very low limit of detection (LOD)=0.347 pg/mL, more particularly, at the low concentration range (1–10 pg/mL). Thus, this developed polypyrrole‐based immunosensor represents a promising strategy for creation of miniaturized label‐free, fast and highly sensitive biosensors for diagnosis of inflammation biomarkers at very low concentrations with reduced cost.     

Studies of Adsorption Kinetics and Defects of Self‐Assembled Thiol Monolayers on Gold by Capacitance Plane Plot

The capacitive property of an electrode/electrolyte interface can be described by complex capacitance. The capacitance plane plots (CPPs) of ideal polarized and kinetic controlled electrodes are derived based on the concept of complex capacitance. By using CPPs, the capacitance of electrode/electrolyte interface can be conveniently determined. In this work, CPPs obtained in ac impedance experiments are employed for the first time in studying the kinetics of adsorption process of the thiol monolayer. The coverage of octadecanethiol (ODT) monolayer on gold is examined as a function of adsorption time. The adsorption process of ODT molecules on gold exhibits two distinct phases: an initial rapid step followed by a slow one. The simple Langmuir model best explains our experimental data in the initial adsorption stage. CPPs and cyclic voltammetry (CV) indicate that, in the initial adsorption step, the ODT monolayer contains defects whose number decreases with the increasing of adsorption time.