Current status and prospects of biosensor technology development

Since Clark and Lyon proposed the idea of ​​biosensors in the 1960s , the development of biosensors has a history of more than 40 years. As an interdisciplinary subject developed between life science and information science, biosensors have been deeply valued and widely used in fermentation technology, environmental monitoring, food engineering, clinical medicine, military and military medicine. With the further informatization of society, biosensors will be more and more widely used. 1. Definition of biosensors and review of their development history As a living being, one of the most basic characteristics is the ability to respond to various external stimuli. The reason why this is possible is firstly because organisms can sense various external stimulus signals and convert these signals into signals that can be received and processed by the information processing system in the body. For example, people can convert external light, sound temperature and other chemical and physical signals into signals that can be received and processed by the information processing system such as the human nervous system through sensory organs such as eyes, ears, nose, tongue, and body. In the modern and future information society, the information processing system must respond to various changes in nature and society. First, it needs to use sensors to receive and convert various external information into signals that can be received and processed by the information processing unit (i.e., computer) in the information system. Biosensors are defined as "devices that use immobilized biomolecules combined with transducers to detect environmental chemicals inside or outside the body or to produce responses after specific interactions with them." Biosensors are composed of two main key parts. One is the molecular recognition component from biological molecules, tissue parts or individual cells, which is the signal receiving or generating part of the biosensor. The other is the hardware instrument component, which is mainly a physical signal conversion component. Therefore, how to separate, purify or even design and synthesize specific biologically active molecules (biological active materials) by biochemical methods, and combine them with accurate and fast-responding physical transducers (transducers) to form a biosensor reaction system is the main purpose of studying biosensors. As mentioned above, biosensors can be called tissue sensors, cell sensors, enzyme sensors, etc. according to the life substances used in their receptors. They can also be named thermal sensors, light sensors, insulin sensors, etc. according to the physical quantity, chemical quantity or biological quantity monitored. They can also be collectively called immunosensors according to their uses. Drug sensors, etc. There is no essential difference between the signal converters in biosensors and traditional converters. For example, electrochemical electrodes, field effect tubes, thermocouples, piezoelectric devices, photoelectric devices and other devices can be used as signal converters in biosensors. Biosensors can also be classified according to different signal converters, such as piezoelectric crystal biosensors, field effect tube biosensors, etc. Since Clark and Lyon proposed the concept of enzyme electrodes in 1962, YSI has actively invested in commercial development and production in the 1970s, and launched the first generation of biosensors in the medical examination market in 1979. The earliest product was enzyme electrodes for blood sugar testing. The successful listing of YSI is closely related to the vigorous development of the electronic information industry in the 1980s, and it has led to a boom in the research and development of biosensors. Medisense continued to focus on the development of the first generation of enzyme electrodes. In 1988, it became famous for the successful development of mediator molecules to accelerate response time and enhance test sensitivity. After the launch of its portable small biosensor products in the pen type (Pen 2) and credit card type (companion 2) in 1988, it immediately captured more than 70% of the first generation product market and became the leader of the biosensor industry. The second generation of biosensors is defined as using antibodies or receptor proteins as molecular recognition components, and the selection of transducers is more diverse, such as field effect semiconductors (FET), optical fibers (FOS), piezoelectric transistors (PZ), surface acoustic wave devices (SAW), etc. Although the second generation of biosensors has attracted widespread research and development interest since the mid-1980s, it is generally believed that it has not yet reached the stage of medical application, and the relevant technology is expected to mature before the end of the century. Currently, the second generation of biosensor products are BIAcore and BIAlite launched by Swedish company Pharmacia in 1991. In 1985, Pharmacia successfully developed the surface film resonance technology (SPR, Surface Plasma Resonance), using this optical property to develop a real-time detection biosensor instrument that can detect the interaction between biomolecules at low concentrations of 10-6g/ml to 10-11g/ml. The third generation of biosensors is positioned to be more portable, automated , and real-time. 2. Classification of biosensors Biosensor microbial electronic products (bioelectronic product). In order to obtain the best signal transmission, the fixed biological component is usually tightly connected with the signal conversion component. Basically, the different modes of signal generation can distinguish biosensors into two main types: 1. Bioaffinity sensors (Bioaffinity sensors) When the fixed biological component and the analyte to be measured undergo affinity binding (bioaffinity binding), the shape of the biomolecule changes and/or causes changes in physical quantities such as charge, thickness, mass, heat or optics. This type of biosensor that uses molecular recognition-binding includes immunosensors, chemical receptor sensors, etc., and its analysis can be hormones, proteins, carbohydrates, antigens or antibodies, and the corresponding receptors can be hormone receptors, dyes, lectins, antibodies or antigens, etc. 2. Biocatalytic biosensors The signal detection of this type of sensor does not lie in the molecular recognition-binding stage, but when the fixed molecule reacts with the analyte, biochemical metabolites are produced, and then the specific metabolites are detected by specific electrodes and expressed as electronic signals. The most familiar is the enzyme electrode, which belongs to the first generation of biosensors. At present, the two main research and development directions of this type of biosensor are (1) using enzyme conjugates, cycling enzymes and series enzymes to combine biosensors, and (2) using microbial cells or animal and plant tissue slices or permeable cells as molecular recognition components. 3. The main application areas of biosensors at present 1. Fermentation industry Because there are often substances that interfere with enzymes during the fermentation process, and the fermentation liquid is often not clear and transparent, it is not suitable for spectral and other methods of measurement. The application of microbial sensors is very likely to eliminate interference and is not limited by the turbidity of the fermentation liquid. At the same time, since the fermentation industry is a large-scale production, the low cost and simple equipment of microbial sensors give it great advantages. Therefore, microbial sensors with low cost, simple equipment, no restrictions on the turbidity of the fermentation liquid, and the ability to eliminate the interference of interfering substances in the fermentation process have been widely used in the fermentation industry. 2. Food industry

































Biosensors can be used to detect the content of nutrients and harmful ingredients in food, the freshness of food, etc. For example, the enzyme electrode biosensor that has been developed can be used to analyze the glucose content in white wine, apple juice, jam and honey, thereby measuring the maturity of fruit. The current-type sulfur dioxide enzyme electrode made of sulfite oxidase as the sensitive material can be used to determine the sulfite content in food. In addition, there are also applications of using biosensors to measure pigments and emulsifiers.

3. Medical field

Biosensors are also playing an increasingly important role in the medical field: clinically, biosensors such as immunosensors are used to detect various chemical components in body fluids to provide a basis for doctors' diagnosis; in military medicine, timely and rapid detection of biological toxins is an effective measure to defend against biological weapons. Biosensors have been used to monitor a variety of bacteria, viruses and their toxins. Biosensors can also be used to measure various amino acids such as acetic acid, lactic acid, lactose, uric acid, urea, antibiotics, glutamic acid, and various carcinogenic and mutagenic substances.

4. Environmental monitoring

Environmental issues have attracted widespread global attention, and the market for professional instruments for environmental monitoring is also growing. At present, a considerable number of biosensors have been put into the monitoring of various pollutants in the atmosphere and water. In developed countries such as the United Kingdom, France, Germany, Spain and Sweden, bioluminescent biosensors are used in the water quality testing process. Biosensors have the advantages of fast and continuous online monitoring, and I believe that they will have more extensive applications in the future.

4. Future Prospects

Biosensors are a multidisciplinary high-tech field. With the rapid development of related disciplines such as biological sciences, information sciences and materials sciences, the development of biosensors will have the following new features:

1. More comprehensive functions and miniaturization

Future biosensors will further involve various fields of medical care, food testing, environmental monitoring, and fermentation industry. One of the important contents of current biosensor research is to study biosensors that can replace biological sensory organs such as vision, hearing and touch, that is, bionic sensors. Moreover, with the advancement of micro-processing technology and nanotechnology, biosensors will continue to be miniaturized, and the emergence of various portable biosensors has made people in front of them.

2. Higher degree of intelligence

In the future, biosensors will be perfectly integrated with computers, able to automatically collect and process data, provide results more scientifically and accurately, and realize sampling, injection, and ultimately form an automated system for detection. At the same time, chip technology will increasingly enter the sensor field, realizing the integration and integration of detection systems.

However, in order for biosensors to be accepted by the market as soon as possible, the following conditions must be met:

(1) Sufficient sensitivity and accuracy.
(2) Simple operation.
(3) Low price and easy mass production.
(4) Quality monitoring during the production process.
(5) Long service life.

I believe that with the further improvement of some key technologies (such as immobilization technology), with the continuous deepening of people's understanding of organisms, and with the continuous development of various disciplines, biosensors will surely play a greater role in the future.