Wide range of biosensor applications

Sensors have already penetrated into an extremely wide range of fields such as industrial production, space development, ocean exploration, environmental protection, resource investigation, medical diagnosis, biological engineering, and even cultural relic protection. It is no exaggeration to say that from vast space to vast oceans and even complex engineering systems, almost every modern project cannot be separated from a variety of sensors.

Reporter: The sensor classification is various. What kind of sensor is the DNA molecule that we mentioned?

Liu Zhongming: This kind of sensor is called a gene sensor and it is a type of biosensor.

A DNA biosensor is a sensing device that converts 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 sample contains the target DNA to be measured, and the transducer converts the signal perceived by the identification element into signals that can be observed and recorded (such as current magnitude, frequency change, fluorescence and chemiluminescence intensity, and light absorption degree). Wait). Normally, a single-stranded DNA is solidified on a transducer, DNA is hybridized, and another DNA containing a complementary sequence is recognized (base pairing principle) to form a stable double-stranded DNA, through acoustic, optical, and electrical signals. The conversion of the target DNA is detected.

Reporter: How does it extend our senses for us?

Liu Zhongming: Its principle is through a single-stranded DNA molecule (also called ssDNA probe) and another complementary ss-DNA molecule (also known as a ssDNA probe) immobilized on the surface of a sensor or transducer probe. The target DNA) hybridizes and the resulting double-stranded DNA exhibits a certain physical signal that is finally reflected by the transducer.

Next, I use DNA electrochemical sensors to detect genetic damage as an example, for everyone to explain in detail how it works. DNA base complementation is selective and specific, so we often use the complementary strand of the DNA (target DNA) that we need to detect as a probe. When the complementary pairing of the probe and the target DNA base is successful, the current through the DNA strand changes accordingly, and the electrical signal changes. This change prompts us that the two have been consistent with each other. From another point of view, if the electrical signal does not change, it implies that there may be damage to this piece of DNA.

To put it plainly, it's like stacking copper coins together. If they are properly aligned, they can conduct electricity. If one of the stacks of coins fails or is not put out well, the conductivity will decrease. If the base pair is misaligned or there is a possible carcinogenic injury, the circuit will be disrupted and current will not flow.

It's like opening a lock with a key. If the key and the shape of the lock's notch match, we know that the two are mismatched and the lock may have a problem. If their shapes match, the lock's attributes can be determined by the label on the key.

Sensitive, fast, and accurate Ideal for medical tests Reporter: DNA molecules are very tiny and fragile. How do we fix and use it?

Liu Zhongming: The issue you are talking about is very important. The immobilization of bio-sensitive materials is an important part of genetic sensor research and is also the key to the preparation of biosensors. This technology determines the function, performance and quality of the sensor. Specifically, it is also related to the sensitivity, linear range, stability, and service life of the sensor. There are several major methods for immobilizing DNA probes such as covalent bonding, self-assembled membranes, electroassembly, and surface enrichment.

The covalent bonding method is a method in which a bioactive molecule is bound to an electrode surface by a covalent bond. Before the electrode is fixed, the electrode is first subjected to activation pretreatment, and then an active bonding group (such as amino group, carboxyl group, etc.) is introduced, and then surface covalent bonding is performed to fix the probe molecule containing a predetermined functional group to the electrode surface.

Of course, we also use the self-assembly method to fix DNA. This technique generally uses a DNA fragment with a sulfhydryl group to form a self-assembled monolayer on the surface of the gold electrode to immobilize the nucleic acid probe.

There are several other commonly used methods, I will not introduce one by one here.

Reporter: As a kind of biosensor, DNA sensor has distinctive characteristics.

Liu Zhongming: DNA sensors are a special class of sensors that have grown up on the basis of infiltration of various disciplines such as biology, chemistry, physics, medicine, and electronics. It has a strong specificity, and has a very high specific recognition ability between the double strands of DNA molecules. The analysis speed is fast and results can be obtained in 1 minute. The accuracy is high and the error is minimal. The operating system is relatively simple and it is easy to implement automatic analysis. Low, the measurement is inexpensive when used continuously. In particular, it is highly automated, miniaturized and integrated.

Reporter: Compared with other fields, the application of DNA sensors in clinical medicine is closer to us and more important to everyone. Can you discuss the application in this area?

Liu Zhongming: With the development of molecular biology, people gradually realize that except for injury, all diseases including infectious diseases, genetic diseases, and malignant tumors are related to genes. Therefore, DNA sensors used in gene detection appear to be Very important.

For example, Hepatitis B is an infectious disease caused by Hepatitis B Virus (HBV), which has a rapid spread, a long incubation period, and a wide range of harm. China's chronic asymptomatic HBV infection or chronic asymptomatic HBV carriers have exceeded 120 million, which is HBV infection. There are the largest number of people in the group. If the self-assembled monolayer membrane technology I described above is used, the single-stranded DNA probe of the probe labeled with hexyl group is immobilized on the surface of the gold electrode to prepare a DNA electrochemical sensor with an electroactive substance as an indicator. A DNA sensor with good specificity, high sensitivity, and short response time can be obtained. It responds better to the hepatitis B virus DNA in serum samples. In other words, DNA sensors can help us detect whether the subject has been infected with chronic asymptomatic HBV correctly or quickly and with high quality.

Many industries require a wide range of applications. Reporter: In addition to clinical medicine, what are the application areas of biosensors?

Liu Zhongming: Biosensors have achieved encouraging development in recent decades. In particular, after the combination of molecular biology and microelectronics, optoelectronics, microfabrication technology, and nanotechnology, new disciplines and new technologies are combined, this kind of development is accelerating, and in various sectors of the national economy, such as food, pharmaceutical, chemical, and clinical Areas such as inspection, biomedicine, and environmental monitoring have revealed a wide range of applications.

For example, glucose content is an important indicator of fruit maturity and shelf life, and biosensors have been developed to analyze glucose in white wine, apple juice, jam and honey. The detection of freshness of foods, especially fish and meat, in the food industry is a major indicator for evaluating food quality. A sensor has been developed to measure the concentration of substances such as inosine monophosphate produced during the degradation of fish and to evaluate the freshness of the fish.

In recent years, the problem of environmental pollution has become increasingly serious, and people are eager to have an instrument capable of continuous, rapid, and on-line monitoring of pollutants. Biosensors meet people's requirements. At present, a considerable number of biosensors have been used in water environment monitoring, atmospheric environment monitoring and other fields.

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

Reporter: What do you think is the future direction of development in this research field?

Liu Zhongming: Now, the research of sensors needs to seek new breakthroughs in stability and reliability. Only by creating more stable and reliable biosensors will the application of clinical testing be greatly expanded.

In addition, the sensor will also develop in the direction of miniaturization and integration. With the advancement of microfabrication technology and nanotechnology, biosensors will continue to be miniaturized, and the emergence of various portable biosensors will make it possible for people to conduct disease diagnosis at home and directly detect foods in the market. In addition, the future biosensors must be tightly integrated with the computer to automatically collect data and process data, provide scientific and more accurate results, realize sampling, sample injection, and result-combined results, and form an automated detection system. With the continuous deepening of research in these two directions and the gradual decline in product costs, biosensors that have demonstrated tremendous application prospects in the laboratory will also “fly into the homes of ordinary people”.