Chemical sensors & biosensorsThere is a huge variety of different chemical sensors, especially if one includes biosensors as a sub-class of chemical sensors, as is done here. A large proportion of chemical sensors are based around metal oxide semiconductor field effect transistor (MOSFET) devices. For this reason, the ISFET (ion sensitive field effect transistor) will be discussed in this section. ISFET devices have been around for some time now (since about 1970), so there is quite a bit of literature on them.The term biosensor refers to any sensor that uses an active biological (or sometimes biologically derived) component in the transduction process. This may be a sensory cell taken from a living organism, and mounted on an electrode. Alternatively, antibodies may be used, which will lock on to the material of interest, and hold it in an appropriate position for sensing. A further option is to use an enzyme that catalyses a reaction that can be detected by suitable means. Since there is considerable interest in monitoring blood glucose levels (to provide closed loop control of blood glucose, by means of an artificial pancreas, for diabetics), blood glucose sensors have received much attention. One of these is based on the glucose oxidase enzyme; so this sensor will be outlined. One thing to note is that a lot of research has gone into these sensors; biosensors and blood glucose sensors in particular. Whilst progress has been made, there are still a lot of problems to be solved. One big problem in this area is that the sensor performance drifts or degrades over time, often in unpredictable ways. So the device has to be calibrated regularly, or just before use. Clearly a blood glucose sensor that only gives reliable readings over a period of a hundred days cannot be used in an implanted artificial pancreas. Thus, while there are many potential uses for chemical sensors, their use is often complicated by calibration requirements.
ISFET sensorsISFETs sense the concentration (activity level) of a particular ion in a solution. These devices are generally based on the enhancement mode metal-oxide-semiconductor field effect transistor (MOSFET) structure, shown in figure 6.
 Figure 6. This has a metal gate electrode, insulated from the semiconductor (silicon) wafer by a thin layer of silicon dioxide (oxide). The bulk of the semiconductor (i.e. the substrate) is doped with impurities to make it p-type silicon; in this material current is carried by positive charge carriers called holes (since they are, in fact, the absence of negatively charged electrons; not easy to explain briefly). Either side of the gate are small areas of silicon doped with impurities so that negatively charged electrons are the main carriers in these n-type silicon regions: the source and the drain. n-type and p-type silicon are used to form diodes; current will flow from p-type to n-type, but not the other way round. So to keep the bulk of the silicon substrate from interfering with the transistor (gate, drain, source), this is connected to the most negative part of the circuit (often connected inside the transistor package to the source, so although the device may look symmetrical, you should use it according to the pin-out on the data sheet). When in use, a positive voltage is applied to the gate. This repels holes from the region near the gate, and attracts electrons, forming a small channel between the drain and source where the majority charge carriers are electrons. Current can flow through this channel, the amount of current that can flow depends on how large the channel is, and thus the voltage applied to the gate. In the ISFET, the gate metal is replaced with an ion selective membrane (figure 7), and the device is immersed in a solution. Ions in the solution interact with the ion selective membrane. When there is a high concentration of positive ions in the solution, a lot of them will accumulate on the gate, widening the channel between the source and drain. With a low concentration of positive charged ions, the channel will be narrow.
 Figure 7. In order to ensure that the FET channel is biased to an optimum size, about which sensing can take place, the solution is maintained at a reference potential by an electrode placed in it. Generally the reference potential is adjusted to maintain a constant current flowing from drain to source, so the ionic concentration will be directly related to the solution reference potential with respect to the substrate potential (in the circuit shown in figure 7). One significant problem in the design and fabrication of ISFETs is ensuring that the ion selective membrane adheres to the device. If the integrity of the membrane is compromised, then the device is useless; this problem has considerable effct on the yield (% of functioning devices on a wafer) of the fabrication process.
Enzyme-based biosensorsEnzymes are highly specific in the reactions that they catalyse. If an enzyme can be immobilised on a sensing substrate, and the reaction products detected, then one has the basis of a highly selective biosensor. The enzyme-based biosensor described below is for monitoring glucose levels; this application has received considerable investigation since glucose is important in diabetes, and also in many industrial fermentation processes.The operation of a glucose oxidase based sensor is shown schematically in figure 8. The enzyme is immobilised on a platinum electrode, and covered with a thin polyurethane membrane to protect the enzyme layer, and reduce the dependence of the sensor on blood oxygen levels. Glucose oxidase, in its oxidised form, oxidises glucose entering the sensor to gluconic acid; resulting in the conversion of the enzyme to its reduced form. The enzyme does not remain in this form for long. It interacts with oxygen entering through the membrane. The products of this interaction are the oxidised form of the enzyme, and two hydrogen ions and two oxygen ions. When the platinum electrode is biased to the correct potential, it will reduce one of the oxygen ions so that the end products are oxygen and water; the resulting electrode current can be measured, and will be proportional to the concentration of glucose in the external medium. (Nb/ This is a very much simplified explanation, and there are also many other ways to monitor the reaction).
 Figure 8. One thing to note is that because the various molecules have to physically move through the materials of the sensor, such biosensors can be quite slow to respond to changes in the external medium.
Microelectrodes for neurophysiologyMicroelectrodes of fine wire or electrolyte filled micropipettes have been used for some time to study the nervous system on a cellular (individual neuron) basis. These, in particular the metal wire microelectrodes, are prime targets for the application of microengineering techniques. The small signal amplitudes involved (in the region of 100uV) and high interface impedances (1-10 MOhm at 1 kHz) between the metal and the tissue mean it is advantageous to place the amplifier as close as possible to the recording site. In addition, the characteristics of microfabricated devices can be more reproducible than for hand-made metal wire microelectrodes, and their small size enables the accurate insertion of many recording sites into small volumes of tissue to study networks of neurons, or for neural prosthesis applications.The microelectrodes operate by detecting the electrical potential generated in the tissue near an active nerve fibre, due to action potential currents flowing through the fibre membrane. There are three common types of micromachined microelectrode (figure 9). Array-type microelectrodes (figure 9a) are used to form the floor of cell culture dishes: signals are recorded from neurons which are placed or grown over these. Probe-type microelectrodes (figure 9b) have recording sites on a long thin shank, which is inserted into the tissue under investigation. Regeneration electrodes (figure 9c) are placed between the ends of a severed peripheral nerve trunk; nerve fibres then re-grow (regenerate) through the device.
 Figure 9. These microelectrodes can be quite difficult to use. For array microelectrodes, appropriate cell culture methods have to be developed and practised. Probe types have to be mounted on amplifier boards, and different situations require many different size / shaped probes. Regeneration electrodes have to be fixed to the stumps of the nerve trunk, and require connecting to the outside world. All devices can potentially generate huge amounts of data, which has to be collected and analysed.
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