Biological recognition elements are immobilised on the surface of a transducer or in a membrane. This requires a bioreactor on top of a traditional transducer. The response of a biosensor is determined by four different factors: diffusion of the analyte, reaction products, co-reactants or interfering chemical species, and kinetics of the recognition process.
Various kinds of biosensors are mainly based on:
chemically sensitive semiconductor devices;
thermistors;
chemically mediated electrodes;
surface acoustic waves devices;
piezoelectric microbalances;
and many other individual or hybrid systems such as MEMS. As an example, for a quartz crystal microbalance sensor depicted in Figure 3.10 [44]:
an electrical AC voltage causes the resonator (i.e. the piezo layer) to oscillate;
a target molecule binds with a receptor based on the lock-and-key principle;
resonance frequency changes because of the weight change;
frequency change is translated into an electrical signal and processed further.
Some examples of the transducers used in the design of biosensors are micro-electrodes, combined ion-selective field-effect transistors and micro-electrodes, fibre optodes and luminescence, thermistors and thermocouples, and surface acoustic wave (SAW) delay lines (often used as piezoelectric elements in sensors and modelled using transversal filters) and bulk acoustic wave microbalances.
Figure 3.10 A quartz crystal microbalance sensor; a thin film sample is coated on the top gold electrode of the quartz shear mode resonator (QCM). The QCM is then inserted between the thermopile and the sample chamber. The experiment consists of varying the composition of the gas mixture at constant temperature and observing changes in the resonant frequency and motional resistance of the QCM and the thermal power flowing between the QCM and the aluminium heat sink via the thermopile.
Figure 3.11 (a) An EnzymFET and (b) its electrical output versus urea concentration [50].
Source: Courtesy of Middelhoek, S., and Audet, S.A.: Silicon Sensors, Academic Press Limited.
As an example, a schematic of a semiconductor sensor is illustrated in Figure 3.11. The back side is connected to a urea sensitive ISFET, often called an ENFET (EnzymFET), similar to that shown in Figure 3.11a. In Figure 3.11b the electrical voltage with respect to urea concentration is shown.
These sensors are carefully packaged using biocompatible materials. One of these types is shown in Figure 3.12. The backside is also shown in Figure 3.13.
Since 1962, when the early glucose oxidase electrode-based biosensor was manufactured by Clark and Lyons [45], many other sensors with various technologies and applications have been developed. Vigneshvar et al. [46] present a comprehensive study of biological sensors. Table 3.1 shows a large set of biosensors with their applications including the involved technology. Table 3.2 lists the uses of different biosensors for the diagnosis of various diseases [46].
Figure 3.12 A semiconductor biosensor schematic [51].
Source: Courtesy of John Wiley & Sons.
Figure 3.13 A semiconductor biosensor schematic; backside contacts [51].
Source: Courtesy of John Wiley & Sons.
3.4.2 Emerging Biosensor Technologies
There have been many emerging technologies recently, including those built in mobile handsets for measuring human biological metrics. As an example, a health app which can monitor people's glucose levels without breaking the skin has been developed recently. The so-called Epic app can help people find out if they develop diabetes and need to make lifestyle changes to avoid it. The app can also tell people about their respiration and blood oxygen saturation. SMBG (self-monitored blood glucose) is recommended for all people with diabetes [47, 48]. To alleviate the intrusiveness of the sensors, there is a great appetite among researchers to design contactless sensors. Some of these sensors are introduced in other chapters of this book.
3.5 Conclusions
Sensor technology devices have become more miniaturised, wearable, user-friendly, cost effective, less intrusive, and inclusive, and are often accessible to outpatients and individuals. Human vital signs as well as abnormalities can be captured invasively or noninvasively (and in some cases nonintrusively) by various sensor modalities, some packed together in one package. The new wireless technology in parallel with the advances in high-speed computing systems provides more accurate and accessible health-monitoring systems. Physical, physiological, biological, and other sensor types are fast developing and allow full body screening in all times. Emerging sensor technologies provide constant feedback to individuals and create a safer and healthier world.
Table 3.1 Biosensors, their principle, applications, and bibliography.
| No. | Type | Principle | Applications | Bibliography |
| 1. | Glucose oxidase electrode-based biosensor | Electrochemistry using glucose oxidation | Analysis of glucose in biological sample | Clark and Lyons [45] |
| 2. | HbA1c biosensor |