Role of carbon nanotubes in electroanalytical chemistry: a review

This review covers recent advances in the development of new designs of electrochemical sensors and biosensors that make use of electrode surfaces modification with carbon nanotubes. Applications based on carbon nanotubes-driven electrocatalytic effects, and the construction and analytical usefulness of new hybrid materials with polymers or other nanomaterials will be treated. Moreover, electrochemical detection using carbon nanotubes-modified electrodes as detecting systems in separation techniques such as high performance liquid chromatography (HPLC) or capillary electrophoresis (CE) will be also considered. Finally, the preparation of electrochemical biosensors, including enzyme electrodes, immunosensors and DNA biosensors, in which carbon nanotubes play a significant role in their sensing performance will be separately considered.     

Microcantilever biosensors based on conformational change of proteins

Microcantilevers (MCLs) hold a position as a cost-effective and highly sensitive sensor platform for medical diagnostics, environmental analysis and fast throughput analysis. MCLs are unique in that adsorption of analytes on the microcantilever (MCL) surface changes the surface characteristics of the MCL and results in bending of the MCL. Surface stress due to conformation change of proteins and other polymers has been a recent focus of MCL research. Since conformational changes in proteins can be produced through binding of anylates at specific receptor sites, MCLs that respond to conformational change induced surface stress are promising as transducers of chemical information and are ideal for developing microcantilever-based biosensors. The MCL can also potentially be used to investigate conformational change of proteins induced by non-binding events such as post-translational modification and changes in temperature or pH. This review will provide an overview of MCL biosensors based on conformational change of proteins bound to the MCL surface. The models include conformational change of proteins, proteins on membranes, enzymes, DNA and other polymers.     

Electrochemistry in solids prepared by sol-gel processes

Sol-gel chemistry provides a route to preparing inorganic polymers with ionically conducting properties by room temperature synthetic routes. The products, which are rigid solids, are well-suited as media for conventional electrochemical techniques such as cyclic voltammetry. This property, when combined with their ability to host a wide variety of species, has allowed development of a variety of devices of interest in electrochemistry and analytical chemistry. Examples include cathodes for fuels cells, electrochromic devices, biosensors, and amperometric sensors for analytes in the gas phase. In this review, the emphasis will be on reported applications to analytical chemistry; however, studies on the general properties of these materials and on their use in electrochemical science also will be summarized because they may provide the basis for further development of sensors.     

Sensing lipid bilayer formation and expansion with a microfabricated cantilever array

We show that cantilever array sensors can sense the formation of supported phospholipid bilayers on their surface and that they can monitor changes in mechanical properties of lipid bilayers. Supported lipid bilayers were formed on top of microfabricated cantilevers by vesicle fusion. The formation of bilayers led to a bending of the cantilevers of 70-590 nm comparable to a surface stress of 27-224 mN/m. Physisorption of bilayers of DOPC and other bilayers on the silicon oxide surface of cantilevers led to a tensile bending of about 70 nm whereas formation of chemisorbed bilayers of mixed thiolated (DPPTE) and non-thiolated lipids (DOPC) on the gold side of cantilevers led to a compressive bending of nearly 600 nm which depended on the ratio of DPPTE to DOPC. First results on bending of bilayer-covered cantilevers due to their interaction with the pore-forming peptide melittin are shown. The results demonstrate that cantilever sensors with immobilized bilayers can be used as model systems to investigate mechanical properties of cellular membranes and may be used for screening of membrane processes involving modification, lateral expansion, or contraction of membranes.     

Nanoengineered glycan sensors enabling native glycoprofiling for medicinal applications: towards profiling glycoproteins without labeling or liberation steps

Nanoengineered glycan sensors may help realize the long-held goal of accurate and rapid glycoprotein profiling without labeling or glycan liberation steps. Current methods of profiling oligosaccharides displayed on protein surfaces, such as liquid chromatography, mass spectrometry, capillary electrophoresis, and microarray methods, are limited by sample pretreatment and quantitative accuracy. Microarrayed platforms can be improved with methods that better estimate kinetic parameters rather than simply reporting relative binding information. These quantitative glycan sensors are enabled by an emerging class of nanoengineered materials that differ in their mode of signal transduction from traditional methods. Platforms that respond to mass changes include a quartz crystal microbalance and cantilever sensors. Electronic response can be detected from electrochemical, field effect transistor, and pore impedance sensors. Optical methods include fluorescent frontal affinity chromatography, surface plasmon resonance methods, and fluorescent carbon nanotubes. After a very brief primer on glycobiology and its connection to medicine, these emerging systems are critically reviewed for their potential use as core sensors in future glycoprofiling tools.     

Required technology breakthroughs to assume widely accepted biosensors

Silicon microsensors have been very successful over the last decade in a wide variety of applications. Although commercialization of silicon-based biosensors has been slow, careful applications of microfabrication technologies to the development of biosensors will drive the formation of many new markets. The most promising high-volume, emerging markets include clinical analysis, health care, and environmental. For example, the worldwide sales of clinical sensors are expected to reach several hundreds of millions by 2000, whereas the total worldwide market for biosensors is forecast to reach $1 billion by the year 2000. In this article, an overview of current and potential markets is presented with an emphasis on technological barriers to overcome before biosensors will become more widely accepted. We start by explaining the relative success of physical sensors compared to biosensors. Subsequently, we review several biosensor approaches and techniques and their associated problems. Finally, the markets that these sensors are meant to serve are analyzed.     

Sensing cantilever beam bending by the optical lever technique and its application to surface stress

Cantilever beams, both microscopic and macroscopic, are used as sensors in a great variety of applications. An optical lever system is commonly employed to determine the deflection and thereby the profile of the cantilever under load. The sensitivity of the optical lever must be calibrated, and this is usually achieved by application of a known load or deflection to the free end of the cantilever. When the sensing operation involves a different type of load or a combination of types of loadings, the calibration and the deflection values derived from it become invalid. Here we develop a master equation that permits the true deflection of the cantilever to be obtained simply from the measurement of the apparent deflection for uniformly distributed loadings and end-moment loadings. These loadings are relevant to the uniform adsorption or application of material to the cantilever or the application of a surface stress to the cantilever and should assist experimentalists using the optical lever, such as in the atomic force microscope, to measure cantilever deflections in a great variety of sensing applications. We then apply this treatment to the experimental evaluation of surface stress. Three forms of Stoney's equation that relate the apparent deflection to the surface stress, which is valid for both macroscopic and microscopic experiments, are derived. Analysis of the errors arising from incorrect modeling of the loading conditions of the cantilever currently applied in experiments is also presented. It is shown that the reported literature values for surface stress in microscopic experiments are typically 9% smaller than their true value. For macroscopic experiments, we demonstrate that the added mass of the film or coating generally dominates the measured deflection and must be accounted for accurately if surface stress measurements are to be made. Further, the reported measurements generally use a form of Stoney's equation that is in error, resulting in an overestimation of surface stress by a factor >5.     

Towards single-spot multianalyte molecular beacon biosensors

The separate developments of microarray patterning of DNA oligonucleotides, and of DNA hairpins as sensitive probes for oligonucleotide identification in solution, have had a tremendous impact on basic biological research and clinical applications. Herein, we will discuss several successful efforts to develop oligonucleotide sensors based on the surface immobilization of functionalized DNA hairpins. We also will discuss the development of prototypical single-spot multianalyte “Molecular Beacon” biosensors. Importantly, we show that organic fluorophores will likely be inadequate in moving this technology forward and new approaches, such as the use of nanotechnology, will be needed.     

Electrochemical sensors and biosensors based on redox polymer/carbon nanotube modified electrodes: A review

The aim of this review is to present the contributions to the development of electrochemical sensors and biosensors based on polyphenazine or polytriphenylmethane redox polymers together with carbon nanotubes (CNT) during recent years. Phenazine polymers have been widely used in analytical applications due to their inherent charge transport properties and electrocatalytic effects. At the same time, since the first report on a CNT-based sensor, their application in the electroanalytical chemistry field has demonstrated that the unique structure and properties of CNT are ideal for the design of electrochemical (bio)sensors. We describe here that the specific combination of phenazine/triphenylmethane polymers with CNT leads to an improved performance of the resulting sensing devices, because of their complementary electrical, electrochemical and mechanical properties, and also due to synergistic effects. The preparation of polymer/CNT modified electrodes will be presented together with their electrochemical and surface characterization, with emphasis on the contribution of each component on the overall properties of the modified electrodes. Their importance in analytical chemistry is demonstrated by the numerous applications based on polymer/CNT-driven electrocatalytic effects, and their analytical performance as (bio) sensors is discussed.     

Mechano-transduction of DNA hybridization and dopamine oxidation through electrodeposited chitosan network

While microcantilevers offer exciting opportunities for mechano-detection, they often suffer from limitations in either sensitivity or selectivity. To address these limitations, we electrodeposited a chitosan film onto a cantilever surface and mechano-transduced detection events through the chitosan network. Our first demonstration was the detection of nucleic acid hybridization. In this instance, we electrodeposited the chitosan film onto the cantilever, biofunctionalized the film with oligonucleotide probe, and detected target DNA hybridization by cantilever bending in solution (static mode) or resonant frequency shifts in air (dynamic mode). In both detection modes, we observed a two-order of magnitude increase in sensitivity compared to values reported in literature for DNA immobilized on self-assembled monolayers. In our second demonstration, we coupled electrochemical and mechanical modes to selectively detect the neurotransmitter dopamine. A chitosan-coated cantilever was biased to electrochemically oxidize dopamine solution. Dopamine's oxidation products react with the chitosan film and create a tensile stress of approximately 1.7 MPa, causing substantial cantilever bending. A control experiment was performed with ascorbic acid solution. It was shown that the electrochemical oxidation of ascorbic acid does not lead to reactions with chitosan and does not change cantilever bending. These results suggest that chitosan can confer increased sensitivity and selectivity to microcantilever sensors.     

Recent developments, characteristics, and potential applications of electrochemical biosensors.

The objective of this study is to analyze the technical importance, performance, techniques, advantages, and disadvantages of the biosensors in general and of the electrochemical biosensors in particular. A product of reaction diffuses to the transducer in the first generation biosensors (based on Clark biosensors). The mediated biosensors or second generation biosensors use specific mediators between the reaction and the transducer to improve sensitivity. The second generation biosensors involve two steps: first, there is a redox reaction between enzyme and substrate that is reoxidized by the mediator, and eventually the mediator is oxidized by the electrode. No normal product or mediator diffusion is directly involved in the third generation biosensors, direct biosensors. Based on the type of transducer, current biosensors are divided into optical, mass, thermal, and electrochemical sensors. They are used in medical diagnostics, food quality controls, environmental monitoring, and other applications. These biosensors are also grouped under two broad categories of sensors: direct and indirect detection systems. Moreover, these systems could be further grouped into continuous or batch operation. Therefore, amperometric biosensors and their current applications are focused on more in detail since they are the most commonly used biosensors in monitoring and diagnosing tests in clinical analysis. Problems related to the commercialization of medical, environmental, and industrial biosensors as well as their performance characteristics, their competitiveness in comparison to the conventional analytical tools, and their costs determine the future development of these biosensors.     

Reporter gene bioassays in environmental analysis

In parallel to the continuous development of increasingly more sophisticated physical and chemical analytical technologies for the detection of environmental pollutants, there is a progressively more urgent need also for bioassays which report not only on the presence of a chemical but also on its bioavailability and its biological effects. As a partial fulfillment of that need, there has been a rapid development of biosensors based on genetically engineered bacteria. Such microorganisms typically combine a promoter-operator, which acts as the sensing element, with reporter gene(s) coding for easily detectable proteins. These sensors have the ability to detect global parameters such as stress conditions, toxicity or DNA-damaging agents as well as specific organic and inorganic compounds. The systems described in this review, designed to detect different groups of target chemicals, vary greatly in their detection limits, specificity, response times and more. These variations reflect on their potential applicability which, for most of the constructs described, is presently rather limited. Nevertheless, present trends promise that additional improvements will make microbial biosensors an important tool for future environmental analysis.     

Monitoring the formation of self-assembled monolayers of alkanedithiols using a micromechanical cantilever sensor

Using a micromechanical cantilever device, the surface stress induced during the growth of alkanedithiol (HS(CH2)nSH) monolayers on gold in solution is continuously monitored and reported. Adsorption of alkanedithiols of varying chain lengths is observed and compared to each other, as well as to the adsorption of hydroxyalkanethiols (HS(CH2)nOH) and alkanethiols (HS(CH2)nCH3). The results have revealed a significant change in surface stress on the basis of the chain length of the alkanedithiol. The long-chain (n > 10) alkanedithiol adsorption imposes a tensile stress on the gold-coated surface of the cantilever rather than the compressive stress exhibited by both alkanethiols and short-chain dithiols. Our results suggest a phenomenon in which the two thiols of the alkanedithiol adsorb onto the gold surface forming a loop inducing a tensile stress on the cantilever for long chain lengths. This study shows that micromechanical cantilever sensors can be very valuable tools in the exploration and characterization of self-assembled monolayers.     

Integrated biosensors: Promises and problems

After a brief review of the biosensors area, this paper explores the possibilities of integrating various classes of biosensors on silicon. Of all classes of sensors, electrochemical and bioelectrochemical sensors are the most suitable for integration, although substantial research on the fabrication and understanding of bioactive layers on semiconductor sensors is still required. Optical, gravimetric and thermal sensors could also be integrated to varying extents; however, the cost benefits are not yet very attractive except for immunosensors based on immobilized immunoglobulins. Electrochemical and gravimetric sensors based on silicon show the greatest potential for batch fabrication and could therefore be best suited for disposable sensors. The review ends with a discussion of the technological, functional and conceptual problems associated with integrated biosensors.     

Dual potentiometric and UV/Vis spectrophotometric disposable sensors with dispersion cast polyaniline

Simple conducting polymer–polyaniline-based sensors/biosensors, working either in potentiometric or UV/Vis spectrophotometric mode, are proposed. Disposable sensors were produced by coating polyaniline layers, cast from aqueous dispersion of the polymer nanoparticles, on a transparent plastic polyacetate foil. In the potentiometric mode, polyaniline layers are sensitive to a number of metal cations, while in UV/Vis mode, changes of absorbance were recorded only in case of a chemical reaction of cations with the polymer. Pronounced sensitivity of tested sensors to ammonia was used for potentiometric/spectrophotometric biosensing purposes studied on a model example of urease-based sensors of urea. The highest sensitivity and reproducibility of such sensors were observed in urea concentration ranging from 1 to 10 mM.     

Quartz-crystal sensors for biosensing and chemical analysis

The principle and applications of quartz-crystal sensors based on the three basic concepts for mass, viscosity, and viscoelastic changes are reported. In the general discussion the realization of a resonant frequency-resonant resistance diagram is described in detail. As an example of application to mass sensing, gas sensing with a carbon-coated quartz crystal is reported. Determination of the blood coagulation factor is used as an example of the application to viscosity sensing. As an example of viscoelastic measurement, an ion-exchange polymer-coated quartz crystal is investigated to show that viscoelasticity changes more than mass in the transport process. The possibility of developing new biosensors and chemical sensors is discussed on the basis of these results.     

Electromechanical biosensors for pathogen detection

Rapid and sensitive detection of pathogen is critical for public health, defense and security. Methods such as culture and immunoassays, though highly selective and accurate, are time-consuming and not sufficient for fast decision-making in many situations. Biosensors have been developed to meet the challenges in pathogen detection. This article reviews the development and application of electromechanical biosensors for pathogen detection. It covers the most commonly used electromechanical biosensor systems, specifically quartz crystal microbalances, cantilever sensors and surface wave acoustic sensors. Sensing principles, immobilization of biorecognition elements, and applications to the detection of pathogens in food and water samples are sequentially discussed.

Graphene Field‐Effect Transistors: Electrochemical Gating,Interfacial Capacitance,and Biosensing Applications

Single‐layer graphene has received much attention because of its unique two‐dimensional crystal structure and properties. In this review, we focus on the graphene devices in solution, and their properties that are relevant to chemical and biological applications. We will discuss their charge transport, controlled by electrochemical gates, interfacial and quantum capacitance, charged impurities, and surface potential distribution. The sensitive dependence of graphene charge transport on the surrounding environment points to their potential applications as ultrasensitive chemical sensors and biosensors. The interfacial and quantum capacitance studies are directly relevant to the on‐going effort of creating graphene‐based ultracapacitors for energy storage.