Until now there has been a limited treatment of the study of whole cells (as a biological component) due to the difficulty in connecting transducers to cell populations. This book focuses on several aspects of neural behaviour both in vitro and in vivo, and for the first time, the detection of populations of neurons (rather than single cells) will be presented. The fundamental behaviour and characterization of neurons on various substrates, using a variety of electronic devices such as transistors and microelectrode arrays will be discussed. Future perspectives discussed in the book include artificial intelligence using biological neural networks and nanoneuromedicine. This book will be invaluable to university neuroscience and analytical chemistry departments and students, academics and physicians will benefit from its accessible style and format.
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Dr. Sub Reddy (C.Chem. MRSC) obtained his first class degree in Chemistry from the University of Manchester. He received his Ph.D. in Membrane-based Electrochemical Biosensing from the same University (1996). His post-doctoral research interests have included the development of quartz crystal-based biosensors, operating in the liquid phase (University of Wales, Bangor; 1994-1997) and the development of application-specific odour sensors (UMIST, Manchester; 1997-1998). Dr. Reddy was Senior Lecturer in Applied Analytical Chemistry at the University of Surrey and recently moved to the University of Central Lancashire as Senior Lecturer in Analytical Chemistry. Current research interests include the development of smart, permselective and biocompatible molecular imprinted polymers and membrane materials for the sensor/sample interface and the advancement of smart materials-based electrochemical, quartz crystal and optical sensors for medical, food and environmental applications. He is particularly interested in developing hydrogel-based molecularly imprinted polymers (HydroMIPs) for the determination of protein markers and other biomarkers and construction of biosensors.
Biosensor technology has rapidly expanded into a wide variety of applications in the last few years. Such fields include clinical diagnostics, environmental chemistry, drug discovery and pathogen detection, to name but a few. The structure of these sensors is based on the intimate combination of a biological entity with a transducer capable of generating an electrical signal to provide information on the biological system being studied. Until now there has been a limited treatment of the study of whole cells (as a biological component) due to the difficulty in connecting transducers to cell populations. This book focuses on several aspects of neural behaviour both in vitro and in vivo, and for the first time, the detection of populations of neurons (rather than single cells) will be presented. The fundamental behaviour and characterization of neurons on various substrates, using a variety of electronic devices such as transistors and microelectrode arrays will be discussed. Future perspectives discussed in the book include artificial intelligence using biological neural networks and nanoneuromedicine. The authors have considerable experience in biosensor technology, and have pioneered the study of neural populations using biosensors in collaboration with neurophysiologists and neuroendrocrinologists. This book will be invaluable to university neuroscience and analytical chemistry departments and students, academics and physicians will benefit from its accessible style and format.
Biosensor technology has rapidly expanded into a wide variety of applications in the last few years. Such fields include clinical diagnostics, environmental chemistry, drug discovery and pathogen detection, to name but a few. The structure of these sensors is based on the intimate combination of a biological entity with a transducer capable of generating an electrical signal to provide information on the biological system being studied. Until now there has been a limited treatment of the study of whole cells (as a biological component) due to the difficulty in connecting transducers to cell populations. This book focuses on several aspects of neural behaviour both in vitro and in vivo, and for the first time, the detection of populations of neurons (rather than single cells) will be presented. The fundamental behaviour and characterization of neurons on various substrates, using a variety of electronic devices such as transistors and microelectrode arrays will be discussed. Future perspectives discussed in the book include artificial intelligence using biological neural networks and nanoneuromedicine. The authors have considerable experience in biosensor technology, and have pioneered the study of neural populations using biosensors in collaboration with neurophysiologists and neuroendrocrinologists. This book will be invaluable to university neuroscience and analytical chemistry departments and students, academics and physicians will benefit from its accessible style and format.
Chapter 1 Introduction to Biosensor Technology, 1,
Chapter 2 The Cell-Substrate Surface Interaction, 50,
Chapter 3 Electronic Detection Techniques, 87,
Chapter 4 Nanosensing the Brain, 130,
Chapter 5 The Vibrational Field and Detection of Neuron Behavior, 142,
Chapter 6 The Biomimetic Interface between Brain and Electrodes: Examples in the Design of Neural Prostheses, 172,
Chapter 7 A Look at the Future, 194,
Subject Index, 203,
Introduction to Biosensor Technology
1.1 Sensor Anatomy, Signaling and Properties
The notion of a sensor device is common knowledge to all. The range of these structures in modern times is immense, ranging from simple physical measurements such as temperature to complex devices that incorporate human cells in their design. The number of applications is also numerous including industrial processing, pharmaceutical analysis, automotive operation, military technology and environmental signaling to name just a few areas of use. In this section we introduce the basics of a special branch of sensor technology that deals with the detection of chemicals, with relevance to the research in neuroscience described later in the chapter. The emphasis is on devices, which constitute the main structures employed in biosensor technology, rather than a comprehensive review of the field.
Devices that detect and signal the presence of chemicals have evolved through two different pathways, although the distinction between the two is somewhat arbitrary. The structure is composed of a chemical recognition site attached to a substrate surface which, in turn, is in close proximity and union with a transducer. Such a system can be used to respond selectively to the presence of chemicals we term the target or analyte, either in the gas or liquid phase. The chemical recognition site is often referred to as the receptor or probe. The technology relies on the ability of such a configuration to 'recognize' chemicals through selective binding at the substrate surface of the device with such surface presence being converted into an electrical signal via the particular physics of a transducer. Chemical sensors are generally considered to involve non-biological/biochemical probes in their design and the same is often regarded to be the case for the analyte. A simple example is the well-known tin oxide sensor which responds to gases such as carbon monoxide. In contrast, biosensors are composed of a union between a transducer and biological/ biochemical receptor. A schematic of the structure including transduction types is depicted in Figure 1.1. Note that the probe can consist of a variety of biological entities ranging from antibodies to live biological cells Given that nucleic acids and proteins are chemicals, as are the targets that cells as probes are designed to detect, it is clear that the distinction between chemical- and biosensors is artificial.
Crucial aspects of biosensor technology are the nature of the response of the device with respect to time and whether ancillary chemistry is required in addition to the basic probe in order to achieve a signal. With respect to the former point, there are sensor specialists who take the view that such a device must respond to its analyte in real time. Conversely, the field is often considered to include 'one-test' disposable structures where there is no attempt to conduct a measurement over a period of time, except in a repeated dipstick fashion. The ubiquitous pregnancy and glucose test strips that are widely commercially available constitute examples of this approach to biodetection. The use of an adjunct chemical in addition to the receptor to achieve a transducer signal is often termed tagging or labeling. An example of this strategy is the use of dyes in conjunction with nucleic acid probes in order to produce fluorescent signals. In certain cases, there is insufficient intrinsic fluorescence in nucleic acid molecular probes to allow the direct possibility of detection. The same is true for electrochemical methods where organometallic complexes (of Ru) have to be employed for work with nucleic acids in order to detect redox chemistry. Technology where such an approach is avoided is called 'label-free detection' and is often regarded to be attractive in view of the fact that sensor fabrication becomes a somewhat simpler process.
Additional important technical factors are the possibilities for incorporation of the device in flow-through automation, sensor miniaturization and prevention of non-specific adsorption. Such automation involving standalone systems avoids time-consuming personal intervention and allows rapid data collection and validation. Microfluidic systems offer speed and saving of reagent costs. Nonspecific adsorption of unwanted components on the device surface poses something of an Achilles' heel for biosensor technology. The selectivity and limit of detection of the sensor when used, for example, in blood, serum, urine and tissue will clearly be influenced strongly by interfering components of the biological sample. It appears to be the case that wide scale use of biosensors in, for example, clinical biochemistry, has not occurred primarily because of this issue.
The placement of a solid transducer–probe combination into a biological sample will result in a signal originating from a composite response, Xn, according to the following matrix:
Xn = Sn1C1 + Sn2C2 + ···· SnnCn (1.1)
where C and S values represent the concentration of analyte and interferants in proximity to the device, and the response sensitivities, respectively.
An enormous number of components would be expected to be involved in this equation in terms of biological samples. A sensitive response (e.g. volts or amps) implies maximization of one S value and, for a selective signal, a minimization of all other S values. To a first approximation, it is necessary to trap the analyte on the device surface to allow the sensor response and, as mentioned above, to repel or avoid such binding of all other elements. Accordingly the sensor signal will be a composite of the chemistry of the attachment process and the physical perturbation caused by the probe–analyte complex. This leads to some interesting aspects concerning the nature of the couple between physical chemistry and the transduction process. In certain cases, as will be seen in later sections, the mere presence of the analyte can influence the transducer and the resulting signal is often referred to as a 'mass response'. However, a situation can be envisaged where a structural shift, such as a probe conformational change, and regardless of whether the response is related to final state effects or the change itself, is required for detection to take place. The physical chemistry of transduction in this case is reminiscent of agonist versus antagonist interactions and will be familiar to the biochemist community. All these mechanisms will obviously be an intrinsic component of the sensitivity parameter, Snn, outlined above.
In summary, there are a number of key desirable properties that a biosensor should possess, although some features are of course more important for some applications than others:
• Selectivity or even specificity (see ref. 4 for...
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