What is a biosensor?

Sensors, we often use in daily life and work, but do not know if everyone knows about "biosensors"? This article collects and collates some information, I hope this article can have a relatively large reference value for every reader.

Introduction Biosensors are instruments that are sensitive to biological substances and convert their concentrations into electrical signals for detection. It consists of immobilized bio-sensitive materials as identification elements (including bioactive substances such as enzymes, antibodies, antigens, microorganisms, cells, tissues, and nucleic acids) and appropriate physical and chemical transducers (such as oxygen electrodes, photosensitive tubes, and field effect tubes). Piezoelectric crystals, etc.) and signal amplification devices constitute analysis tools or systems. The biosensor has the functions of a receptor and a converter. Instruments that are sensitive to biological substances and convert their concentrations into electrical signals for detection.

In 1967, SJ Updick and others produced the first biosensor glucose sensor. The glucose oxidase was contained in a polyacrylamide gel to be cured, and the colloidal membrane was fixed on the tip of the diaphragm oxygen electrode to make a glucose sensor. When using other solidified membranes such as enzymes or microorganisms, other sensors that detect their counterparts can be made. The method of fixing the sensation membrane includes a direct chemical binding method; a macromolecular carrier method; and a polymer membrane binding method. Has developed a second generation of biosensors (microorganisms, immune, enzyme immunoassay and organelle sensors), developed and developed third-generation biosensors, and field-effect biosensors that combine system biotechnology with electronics technology, which opened in the 1990s. Flow control technology and microfluidic chip integration of biosensors provide new technology prospects for drug screening and gene diagnosis. Since the enzyme membrane, mitochondrial electron transport system particle membrane, microbial membrane, antigen membrane, and antibody membrane have a selective recognition function on the molecular structure of the biological substance, only a specific reaction serves as a catalytic activation, so the biosensor has a very high selectivity. The disadvantage is that the biocured film is not stable. Biosensors involve biological substances and are mainly used for clinical diagnostic tests, monitoring during treatment, fermentation industry, food industry, environment and robotics.

Biosensors are an interdisciplinary subject that combines biologically active materials (enzymes, proteins, DNA, antibodies, antigens, biofilms, etc.) and physico-chemical transducers. It is an advanced detection method that is essential for the development of biotechnology. And monitoring methods are also fast, micro-analytical methods for the molecular level of matter. In the development of knowledge economy in the 21st century, biosensor technology will inevitably be a new growth point between information and biotechnology, clinical diagnosis, industrial control, food and drug analysis (including biopharmaceutical research and development) in the national economy. There is a wide range of application prospects in environmental protection, biotechnology, and biochip research.

Explain that the sensor is a special device that can acquire and process information. For example, the sensory organ of the human body is a perfect sensor system that senses physical information such as light, sound, temperature, and pressure outside the nose through the eyes, ears, and the skin. Chemical stimuli such as sensational odor and taste. The biosensor is a special type of sensor that uses bioactive units (such as enzymes, antibodies, nucleic acids, cells, etc.) as biosensing units and has highly selective detectors for target analytes. Biosensor is a high-tech that is infiltrated by various disciplines such as biology, chemistry, physics, medicine, and electronics. Due to its excellent selectivity, high sensitivity, fast analysis speed, low cost, continuous on-line monitoring in complex systems, especially its highly automated, miniaturized and integrated features, it has been acquired in recent decades. Vigorous and rapid development. It has broad application prospects in various sectors of the national economy such as food, pharmaceuticals, chemicals, clinical testing, biomedicine, and environmental monitoring. In particular, the integration of new disciplines and technologies such as molecular biology and microelectronics, optoelectronics, microfabrication and nanotechnology is changing the face of traditional medicine and environmental science. The research and development of biosensors has become a new hot spot in the development of science and technology in the world, forming an important part of the emerging high-tech industry in the 21st century, and has important strategic significance.

The sensor that defines the immobilized biological component or organism as a sensor is classified as a biosensor.

Biosensors do not specifically refer to sensors used in the field of biotechnology. Its applications also include environmental monitoring, health care, and food inspection. Biosensors mainly have the following three classification naming methods:

1. According to the biosensor, the molecular recognition element or the sensitive element can be divided into five categories:

Enzyme sensors, microbial sensors, organosensors, tis-sue sensors and immunosensors. Obviously, the sensitive materials used are, in order, enzymes, micro-organisms, organelles, animal and plant tissues, antigens and antibodies.

2. According to a biosensor transducer or a signal converter, a bioelectric sensor, a semiconductor biosensor, an optical biosensor, a calorimetric biosensor, and a piezoelectric biosensor are classified. Etc. The transducers are electrochemical electrodes, semiconductors, photoelectric converters, thermistors, piezoelectric crystals, etc. in this order.

3. The interaction between the measured target and the molecular recognition element is classified as bioaffinity biosensor, metabolized or catalytic biosensor.

The actual interaction between the three classification methods is used.

生物研究[3]Open Journal of Applied Biosensor(OJAB)is an openly accessible journal publishedquarterly.The goal of this journal is to provide a platform for scientists and academicians all over the world to promote, share,and discuss various new issues and Developments in different areas of Biosensor.

Applied Biosensors (OJAB) is a quarterly published open source journal. The purpose of this magazine is to provide a platform to promote scientists and scholars around the world to share and discuss various new issues and developments in biosensors in different fields.

Includes the following research areas:

Biological Materials

Biosensor Applications

Biosensor Fabrication

Biosensor Interfaces and Membrane Technology

Blood Glucose Biosensor

DNA Chips

Instrumentation,Signal Treatment and

Uncertainty Estimation in Biosensors

Lab-on-a-chip Technology in Biosensors

Microfluidic Devices in Biosensors

Nanobiosensors and Nanotechnology Used in Biosensors

Structure Principle The biosensor is composed of a molecular recognition section (sensitive element) and a conversion section (transducer). The molecular recognition section identifies the measured target and is a main functional element that can cause a certain physical change or chemical change. The molecular recognition section is the basis for the selective measurement of biosensors. Among the organisms, substances that can selectively separate specific substances include enzymes, antibodies, tissues, and cells. These molecules recognize the functional substances through the recognition process can be combined with the measured object into a complex, such as the binding of antibodies and antigens, enzyme and matrix binding. When designing a biosensor, it is an extremely important prerequisite to select an identifying functional substance suitable for the measurement object. Take into account the characteristics of the resulting complex. Selecting the transducer based on the chemical change or physical change caused by the molecular recognition of the sensitive element prepared by the functional substance is another important step in the development of a high-quality biosensor. The amount of light, heat, and chemical substances generated or consumed in a sensitive element will produce a corresponding amount of change. Based on these variations, suitable transducers can be selected.

The information generated by the biochemical reaction process is diversified, and the results of microelectronics and modern sensing technologies have provided rich means for detecting this information.

Applications The food industry biosensor's application in food analysis includes the analysis of food ingredients, food additives, harmful toxins, and food freshness.

(1) Food composition analysis In the food industry, glucose content is an important indicator of fruit maturity and shelf life. The enzyme electrode biosensor has been developed to analyze glucose in white wine, apple juice, jam and honey. Other sugars, such as sugar, maltose in beer and wort, also have mature measuring sensors.

Niculescu et al. developed an amperometric biosensor that can be used to detect ethanol content in beverages. This biosensor buries a polyprotein alcohol dehydrogenase in polyethylene. The ratio of enzyme and polymer can affect the performance of the biosensor. In the current experiment, the biosensor has a limit of 1 nmol/L for ethanol.

(2) Analysis of Food Additives Sulfites are commonly used as bleaching agents and preservatives in the food industry. Electrode type sulfoxidase electrodes using sulfite oxidase as a sensitive material can be used to determine sulfite content in foods. The linear range is a negative fourth-order mol/L of 0-6. In addition, such as beverages, puddings, vinegar and other foods in the sweetness, Guibault, etc. using aspartase enzyme binding ammonia electrode determination, the linear range of 2 × 10 negative quintuplicate ~ 1 × 10 negative cubic mol / L. In addition, the use of biosensors for the determination of pigments and emulsifiers has also been reported.

(3) Analysis of Pesticide Residues People pay more and more attention to the problem of pesticide residues in foods, and governments in various countries are constantly strengthening the detection of pesticide residues in foods.

Yamazaki et al. invented an amperometric biosensor using a man-made enzyme for the determination of organophosphorus insecticides. Using an organophosphorus insecticide hydrolase, the limit of determination of p-nitrophenol and diethylphenol was negative 7th. Mol, determined at 40°C for 4 min. Albareda et al. immobilized acetylcholinesterase on the surface of a copper carbon paste electrode using a glutaraldehyde cross-linking method to prepare a negative tens of mol/L of paraoxon and a negative value of 10 at a detectable concentration of 10. The tenth-square-mol/L carbofuran biosensor can be used to directly detect the residues of two pesticides in tap water and juice samples.

(4) Examination of microorganisms and toxins The presence of pathogenic microorganisms in foods will cause great harm to the health of consumers. Toxins in foods are not only of many types but also have high toxicity. Most of them have carcinogenic, teratogenic and mutagenic effects. Detection of pathogenic microorganisms and toxins in food is critical.

Beef is easily infected by E. coli 0157.H7. Therefore, a rapid and sensitive method is required to detect and protect bacteria such as E. coli 0157.H7. Optical fiber biosensors developed by Kramerr et al. can detect pathogens in foods (eg, E. coli 0157.H7.) within minutes, while traditional methods take several days. This biosensor takes only 1 day from detection of the pathogen to regaining the pathogen from the sample and allowing it to grow independently on the medium, compared to 4 days for the traditional method.

There is also a fast and sensitive immune biosensor that can be used to measure the residue of dihydroavermectin in milk. It is based on the cytoplasmic genome response and transmits signals through the optical system. The detection limit that has been reached is 16.2 ng/mL. One can detect 20 milk samples a day.

(5) Detection of freshness of foods Detection of freshness of foods, especially fish and meat, in the food industry is a major indicator for evaluating food quality. Volpe et al. used astragaloside oxidase as a biosensing material combined with a hydrogen peroxide electrode to determine the inosine monophosphate (IMP), inosine (HXR), and hypoxanthine (HX) produced during fish degradation. The concentration, in order to evaluate the freshness of the fish, has a linear range of 5x10 minus 10th power to 2x10 minus 4th power mol/L.

Environmental Monitoring Environmental pollution has become increasingly serious. People are eager to have an instrument that can continuously, quickly, and on-line monitor pollutants. Biosensors meet people's requirements. A considerable number of biosensors have been used in environmental monitoring.

(1) Water environment monitoring Biochemical oxygen demand (BOD) is a widely used comprehensive indicator of the extent of organic pollution. Biochemical oxygen demand is also one of the most commonly used and most important indicators in the monitoring of water bodies and the control of sewage treatment plants. The conventional BOD measurement requires a 5d incubation period, and the operation is complex, and the repeatability is poor, time-consuming and labor-intensive, and the interference is large, and it is not suitable for on-site monitoring. Siya Wakin et al. made a microbial BOD sensor using Trichosporoncutaneum and Bacillus licheniformis. The BOD biosensor can accurately measure glucose and glutamate concentrations simultaneously. The measurement range is 0.5 to 40 mg/L and the sensitivity is 5.84 nA/mgL. The biosensor has good stability. In 58 experiments, the standard deviation is only 0.0362. The required reaction time is 5 to 10 min.

Nitrate ion is one of the major water pollutants. If added to food, it is extremely harmful to human health. Zatsll et al. proposed a method for the detection of nitrate ions by an integrated enzyme-effect FET device. The detection limit of nitrate ion is 7x10 minus 5th power mol, the response time is less than 50s, and the system operating time is about 85s.

In addition, Han et al. invented a novel microbial sensor that can be used to determine trichloroethylene. The sensor immobilized Pseudomonas JI104 on a polytetrafluoroethylene membrane (diameter: 25 mm, pore size: 0.45 μm). The film was then fixed on a chloride ion electrode. The chloride ion electrode with AgCl/Ag2S film (7024L, DKK, Japan) and the Ag/AgCI reference electrode were connected to the ion meter (IOL-50, DKK, Japan), and the change of the recording voltage was compared with the standard curve. The concentration of trichloroethylene. The sensor has a linear concentration range of 0.1 to 4 mg/L and is suitable for the detection of industrial wastewater. Under optimal conditions, the response time is less than 10 minutes.

(2) Atmospheric environment monitoring Sulfur dioxide (S02) is the main cause of the formation of acid rain and the traditional detection method is very complicated. Martyr et al. immobilized subcellular lipids (liver microsomes containing sulfite oxidase) on cellulose acetate membranes, and an oxygen electrode to make an amperometric biosensor, and tested the acid rain acid mist solution formed by S02. lOmin can get stable test results.

NOx is not only one of the causes of the acid rain mist, but also the culprit of photochemical smog. Charles et al. used a microbiological sensor consisting of a porous membrane, immobilized nitrifying bacteria, and an oxygen electrode to determine the nitrite content of the sample, thereby deducing the concentration of NOx in the air. Its detection limit is 0.01xl0 minus 6 power mo1/L.

Fermentation Industry In various biosensors, microbiological sensors have the characteristics of low cost, simple equipment, no limitation on the degree of turbidity of the fermentation broth, and possible elimination of interference from interfering substances in the fermentation process. Therefore, microbial sensors are widely used as an effective measurement tool in the fermentation industry.

(1) Determination of raw materials and metabolites The microbial sensor can be used to measure raw materials (such as molasses, acetic acid, etc.) and metabolites (such as cephalosporin, glutamic acid, formic acid, alcohol, lactic acid, etc.) in the fermentation industry. The measuring device is basically composed of a suitable microbial electrode and an oxygen electrode. The principle is to utilize the assimilation of microorganisms to consume oxygen, and the amount of oxygen reduction is measured by measuring the amount of change in the current of the oxygen electrode so as to achieve the purpose of measuring the concentration of the substrate. .

In 2002, Tkac et al. used a glucose oxidase cell biosensor based on ferricyanide as a medium to measure the ethanol content in the fermentation industry. The measurement was completed in 13 seconds and the measurement sensitivity was 3.5 nA/mM. The microbiological sensor has a detection limit of 0.85 nM, a measurement range of 2 to 270 nM, and good stability. In the continuous 8.5 h test, there was no decrease in sensitivity.

(2) Determination of the number of microbial cells The determination of the number of cells in the fermentation broth is important. The number of cells (cell concentration) is the number of cells in the unit broth. Under normal circumstances, it is necessary to take a certain sample of fermentation broth and determine it by microscopic counting method. This measurement method is time consuming and is not suitable for continuous measurement. There is an urgent need for a simple and continuous method of direct measurement of cell number in fermentation control. It was found that on the surface of the anode (Pt), the bacteria can be directly oxidized and generate electricity. This electrochemical system can be applied to the determination of cell number. The measurement results are similar to those measured by conventional cell counting methods. The use of this electrochemical cell number sensor allows continuous and on-line determination of cell concentration.

Biosensors in medical medicine are playing an increasingly important role. Biosensing technology not only provides a rapid and simple new method for basic medical research and clinical diagnosis, but also has wide application prospects in military medicine because of its uniqueness, sensitivity, and quick response.

(1) Clinical medicine In clinical medicine, enzyme electrodes are the earliest and most widely used sensors and have been successfully applied to the detection of blood glucose, lactic acid, vitamin C, uric acid, urea, glutamic acid, transaminase and other substances. The principle is: using immobilization technology to enclose the enzyme on the bio-sensing membrane. If the sample contains the corresponding enzyme substrate, it can react to produce an acceptable information substance, indicating that the response of the electrode can be converted into the change of the electrical signal. Based on this change, it is possible to determine the presence and quantity of a substance. Microbial sensors can be made by using microorganisms with different biological characteristics instead of enzymes. Microbial sensors used in clinical applications include glucose, acetic acid, and cholesterol sensors. If you choose a suitable tissue containing a certain enzyme, instead of the corresponding enzyme made of the sensor is called a bio-electrode sensor. For example, sensors made from pig kidney, rabbit liver, beef liver, beet, pumpkin, and cucumber leaves can be used to detect glutamine, guanine, hydrogen peroxide, tyrosine, vitamin C, and cystine, respectively.

DNA sensor is one of the most widely reported in biosensors at present. It is the biggest advantage of DNA sensors for clinical disease diagnosis. It can help doctors understand the occurrence and development of diseases from the levels of DNA, RNA, protein and their interactions. Helps in the timely diagnosis and treatment of the disease. In addition, drug testing is a major highlight of DNA sensors. Brabec et al. used DNA sensors to study the mechanism of action of commonly used platinum anticancer drugs and measured the concentration of such drugs in the blood.

(2) In military medical military medicine, timely and rapid detection of biological toxins is an effective measure to prevent biological weapons. Biosensors have been used to monitor a wide variety of bacteria, viruses, and their toxins, such as Bacillus anthracis, Yersinia pestis, Ebola hemorrhagic fever virus, and botulinum toxoids.

In 2000, the U.S. military reported that it has developed an immunosensor that can detect Staphylococcal enterotoxin B, ricin, T. and T. botulinum, and Botox. The detection time was 3 to 10 min and the sensitivity was 10,5 Omg/L, 5x10 5th power, and 5x10 4th power cfu/ml. Song et al. made a biosensor for detecting cholera virus. The biosensor can detect cholera toxin less than 1xlO in 5min mol/L within 30min, and has high sensitivity and selectivity, and the operation is simple. This method can be used for the detection of protein toxins and pathogens with multiple signal recognition sites.

In addition, in forensics, biosensors can be used for DNA identification and parent-child certification.

Application Examples There are many potential applications for various types of sensors. The demand for biosensors in the research and commercial fields comes mainly from the identification of specific target molecules, the practicality of biometric components, and disposable detection systems that are superior to laboratory techniques in some cases. Here are some examples:

Diabetic blood glucose monitoring, motivation from market demand Other medical-related goals:

Environmental applications such as pesticide testing and river contamination testing;

Telemetry of airborne bacteria, such as activities against bioterrorism;

Detection of pathogens;

Determination of the amount of toxin before and after bioremediation;

Organic phosphate detection and quantitative analysis;

Routine analysis of folic acid, microbial H, vitamin B12, and pantothenate, substituting microbial identification;

Determination of food residues in foods, especially meat and honey, such as antibiotics and growth promoting hormones;

Drug development and evaluation of biological activity of new compounds.

Case 1. Application to detect glucose concentration Researchers at Purdue University and other institutions in the United States have developed a new type of biosensor that can perform non-invasive diabetes tests to detect extremely low glucose concentrations in human saliva and tears. This technique does not require tedious production steps, which can reduce the manufacturing cost of the sensor and may help eliminate or reduce the chance of using acupuncture for diabetes testing.

Features (1) Immobilized bioactive substances are used as catalysts, and valuable reagents can be used repeatedly, which overcomes the disadvantages of high enzymatic assay reagent costs and complicated and complicated chemical analysis.

(2) Strong in specificity, responding only to specific substrates, and not affected by color or turbidity.

(3) The analysis speed is fast, and results can be obtained in one minute.

(4) High accuracy, generally relative error can reach 1%.

(5) The operating system is relatively simple and easy to implement automatic analysis.

(6) The cost is low. In continuous use, only a few cents of RMB are required for each measurement.

(7) Some biosensors can reliably indicate oxygen supply status and by-products in a microbial culture system. In the production control, many complex physical and chemical sensors can be obtained to obtain information. At the same time, they also indicate the direction to increase the yield of the product.

Overview of Prospects With the development of biological sciences, information sciences, and materials sciences, biosensor technology is rapidly developing. However, at present, the widespread application of biosensors still faces some difficulties. In the future, biosensors will focus on the selection of biosensing elements with high activity and selectivity; improving the service life of signal detectors; The useful life of signal converters; the stability of biological responses and the miniaturization and portability of biosensors. It can be foreseen that future biosensors will have the following features.

Diversification of functions Future biosensors will further involve various areas of healthcare, disease diagnosis, food testing, environmental monitoring, and fermentation industries. One of the important contents of biosensor research is to study biosensors that can replace the sensory organs such as biological vision, sense of smell, taste, hearing and touch. This is a bionic sensor, also called a biosensor modeled on a biological system.

Miniaturization With the advancement of microfabrication technology and nanotechnology, biosensors will continue to be miniaturized, and the emergence of various portable biosensors will enable people to diagnose diseases at home, making it possible to directly detect foods in the market.

Intelligent and integrated future biosensors must be tightly integrated with the computer, automatically collect data and process data, provide scientific and more accurate results, realize sampling, sample injection, and result-based integration, and form an automated detection system. At the same time, the chip technology will increasingly enter the sensor to realize the integration and integration of the detection system.

The continuous advancement of low-cost, high-sensitivity, high-stability, and long-life biosensor technologies will inevitably require continuous reduction in product cost and increase in sensitivity, stability, and longevity. Improvements in these characteristics will also accelerate the marketization and commercialization of biosensors. In the near future, biosensors will bring tremendous changes to people's lives. It has broad application prospects and will surely shine in the market.

Biosensors are practical components of organisms (enzymes, antigens, antibodies, hormones, DNA) or the organism itself (cells, organelles, tissues). They can specifically recognize and react with various analytes; the latter have Electrochemical electrodes, ion-sensitive field effect transistors (ISFET), thermistors, photocells, optical fibers, piezoelectric crystals (PZ), etc., function to convert biosensor signals sensed by sensitive elements into measurable electrical signals.

Biosensors can be divided into enzyme sensors, microbial sensors, tissue sensors, organelle sensors, and immunosensors according to the different molecular recognition elements used; they can be divided into electrochemical biosensors, semiconductor biosensors, and heat sensors, depending on the signal conversion elements. Biosensors, photometric biosensors, acoustic biosensors, etc.; can be divided into potential biosensors, current biosensors, and voltammetric biosensors based on different measurement methods for output electrical signals. Microbial sensors are an important branch of biosensors. In 1975, Divies produced the first microbial sensor, which opened up yet another new area for the development of biosensors.

Without damaging the function of microorganisms, microorganisms can be immobilized on a carrier to make a microbial sensor. Compared with enzyme sensors, microbial sensors have the following features:

(1) The strain of microorganism is much lower than the price of separating and purifying the enzyme, thus the manufactured sensor is easy to popularize;

(2) The activity of the enzymes in the microbial cells is not easy to reduce under the proper environment, so the life of the microbial sensors is longer;

(3) Even if the catalytic activity of the enzyme in the microorganism has been lost, it can be regenerated by the proliferation of cells;

(4) For complex continuous reactions that require cofactors, it is easier to use microbes to perform DNA biosensors. DNA biosensors are sensing devices that turn the presence of target DNA into detectable electrical signals. It consists of two parts, one is the identification element, that is DNA probe, and the other is the transducer. The identification element is mainly used to sense whether the target DNA in the sample is contained in the sample; the transducer converts the signal perceived by the identification element into a signal that can be observed and recorded. Normally, a single-stranded DNA is solidified on a transducer, DNA is hybridized, another DNA containing a complementary sequence is recognized, and a stable double-stranded DNA is formed, and the target DNA is processed through conversion of sound, light, and electrical signals. Testing.

The principle of the DNA biosensor is that the double-stranded DNA formed by the hybridization between a single-stranded DNA molecule with a known nucleotide sequence fixed on the surface of the sensor or transducer probe and another complementary ss-DNA molecule will exhibit a certain degree of The physical signal is finally reflected by the transducer.

In summary, this article has already explained the biosensors. I believe that everyone is getting more and more in-depth knowledge of biosensors. I hope this article will have a relatively large reference value for readers.