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CMOS-based sensors offer significant advantages to life science applications, such as non-invasive long-term recordings, fast responses and label-free processes. They have been widely applied in many biological and medical fields for the study of living cell samples such as neural cell recording and stimulation, monitoring metabolic activity, cell manipulation, and extracellular pH monitoring. Compared to other sensing techniques, capacitive sensors are low-complexity, high-precision, label-free sensing methods for monitoring cellular activities such as cell viability, proliferation and morphology. The development of capacitive sensors for use in life sciences requires thorough knowledge of both the intended biological applications and CMOS circuitry. This book addresses the principles, design, implementation and testing, and packaging of CMOS circuits for these applications. Existing applications, markets, and potential future developments are also covered, plus the relevant biological protocols. Emerging CMOS Capacitive Sensors for Biomedical Applications provides information and guidance for researchers and advanced students in the field of microelectronics who are looking to specialise in biological applications. It is also relevant to academic and industrial researchers already working in the biosensors field, who wish to expand their knowledge and keep abreast of new developments.
1.1 Overview of Lab-on-Chip Laboratory-on-Chip (LoC) is a multidisciplinary approach used for the miniaturization, integration and automation of biological assays or procedures in analytical chemistry [1-3]. Biology and chemistry are experimental sciences that are continuing to evolve and develop new protocols. Each protocol offers step-by-step laboratory instructions, lists of the necessary equipments and required biological and/or chemical substances [4-7]. A biological or chemical laboratory contains various pieces of equipment used for performing such protocols and, as shown in Fig. 1.1, the engineering aspect of LoC design is aiming to embed all these components in a single chip for single-purpose applications. 1.1.1 Main Objectives of LoC Systems Several clear advantages of this technology over conventional approaches, including portability, full automation, ease of operation, low sample consumption and fast assays time, make LoC suitable for many applications including. 1.1.1.1 Highly Throughput Screening To conduct an experiment, a researcher fills a well with the required biological or chemical analytes and keeps the sample in an incubator for some time to allowing the sample to react properly. Afterwards, any changes can be observed using a microscope. In order to quickly conduct millions of biochemical or pharmacolo- cal tests, the researchers will require an automated highly throughput screening (HTS) [8], comprised of a large array of wells, liquid handling devices (e.g., mic- channel, micropump and microvalves [9-11]), a fully controllable incubator and an integrated sensor array, along with the appropriate readout system.
1.1 Overview of Lab-on-Chip Laboratory-on-Chip (LoC) is a multidisciplinary approach used for the miniaturization, integration and automation of biological assays or procedures in analytical chemistry [1-3]. Biology and chemistry are experimental sciences that are continuing to evolve and develop new protocols. Each protocol offers step-by-step laboratory instructions, lists of the necessary equipments and required biological and/or chemical substances [4-7]. A biological or chemical laboratory contains various pieces of equipment used for performing such protocols and, as shown in Fig. 1.1, the engineering aspect of LoC design is aiming to embed all these components in a single chip for single-purpose applications. 1.1.1 Main Objectives of LoC Systems Several clear advantages of this technology over conventional approaches, including portability, full automation, ease of operation, low sample consumption and fast assays time, make LoC suitable for many applications including. 1.1.1.1 Highly Throughput Screening To conduct an experiment, a researcher fills a well with the required biological or chemical analytes and keeps the sample in an incubator for some time to allowing the sample to react properly. Afterwards, any changes can be observed using a microscope. In order to quickly conduct millions of biochemical or pharmacolo- cal tests, the researchers will require an automated highly throughput screening (HTS) [8], comprised of a large array of wells, liquid handling devices (e.g., mic- channel, micropump and microvalves [9-11]), a fully controllable incubator and an integrated sensor array, along with the appropriate readout system.
Biochips incorporate a verity of means including electronic, photonic and microfluidic devices; biological materials (living cells, tissue, enzymes, nucleic acid and etc.) and chemical analysis to produce the detectable signals for identification of biological phenomena. Among several competing biochip technologies, Complementary Metal Oxide Semiconductor (CMOS) process offers the advantages of low cost, integrated, high precision and portable techniques suitable for point-of-care diagnostics. Advanced CMOS Biochip takes multi-path approach: microelectronic design and implementation of bio-interfaces offering a vital contemporary view of a wide range of integrated circuits and system for electrical, magnetic, optical and mechanical sensing and actuating blocks and much more; classical knowledge of biology, biochemistry as well as microfluidics. The coverage is both practical and in depth integrating experimental, theoretical and simulation examples. By using Advanced CMOS Biochip, readers will have the fundamentals and design techniques to grasp the situation which arise typically in CMOS biochip devices.
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