BIOSENSORS: INTRODUCTION & BIOLOGICAL PRINCIPLES
Shiviya Raina
BS-MS 4th year, Biological sciences
To have the ability to monitor the health status of a patient, disease onset and progression and the outcome of treatment in a non-invasive manner is the main aim of research in health care and hence in recent years, the demand has grown for simple and disposable devices that also demonstrate fast response times, are user-friendly, cost-efficient, and are suitable for mass production and biosensors seem to meet almost all of these criteria. It has been established by several studies that Diabetes mellitus is the leading cause of morbidity and mortality worldwide. One of the approaches to manage diabetes is self-monitoring of blood glucose concentration and thus there is a requirement of devices that measure the same. Glucose biosensors have taken over this market and their demand is growing by the day. Glucose biosensors are just one example of the numerous applications biosensors have in the field of environmental monitoring, food control, drug discovery, forensics, and biomedical research.
Leland C. Clark, Jr developed the first true biosensor in 1956 for oxygen detection and is known as the 'father of biosensors’. This was followed by the discovery of biosensors for the detection of glucose and urea. Eventually, in 1975 the first commercial biosensor was developed by Yellow Spring Instruments (YSI).
So, what exactly is a biosensor?
It is simply, a device used for quantification of a particular analyte in a biological or chemical reaction. It generates signals proportional to the concentration of the particular analyte and consists of a biological recognition system and a transducer for signal processing. The biological recognition system interacts with the analyte, and this biological response is converted into an electrical signal by the transducer. A typical biosensor has the following components.
1. Analyte - It is the substance of interest that needs to be detected and quantified. Like in the case of a biosensor detecting urea, the analyte is 'urea'.
2. Bioreceptors/Biological Recognition Element - It is a biological element or molecule that recognizes the analyte specifically. To prevent interference from other molecules, it is necessary that bioreceptors are selective in nature. This means that in a sample containing other molecules, the receptor should be specifically able to recognize the analyte of interest. The process of signal generation upon the interaction of bioreceptor with the analyte is called bio-recognition. Some examples of bioreceptors are- Enzyme, Antibody, DNA, and cell.
3. Transducer - It is a device that converts a signal from one form of energy to another. It can convert physical, chemical, or biological stimuli into electrical signals. In this case, the transducer converts the energy from the bio-recognition event into a measurable signal. This process is known as signalization. Optical transducers, electrochemical transducers, and piezoelectric material are some of the transducers used in biosensors.
4. Electronics - This part consists of electronic circuitry that is involved in the processing of signals so that it can be displayed. The processing of signal involves amplification and conversion of signals from analog into the digital form.
5. Display - In this part, the results are generated in a user-friendly manner that is easy to read and interpret. According to the requirement specified by the user, the output can be in the form of a graph, numeric value, tabular format, or an image.
Schematic of a typical Biosensor
Different types of biosensors based on the bioreceptors used are as follows:
1. Enzyme-based biosensors - This bioreceptor is based on the specific binding capabilities of the enzyme to its substrate and their catalytic abilities. In this case, there are several mechanisms by which the analyte can be detected -
● Conversion of the analyte by the enzyme into a form detectable by the sensor
● Enzyme inhibition or activation by the analyte
● Modification of enzyme properties
2. Electrochemical immunosensors - They involve the use of antigen or antibodies as the bioreceptors. The basis of this biosensor is the specific binding affinity of the antibody to its antigen and formation of a stable antigen-antibody complex. The interaction of antigen and antibody can be thought of that as of a lock and key where the antigen will only fit into the antibody if it has the right conformation. These biosensors are widely used for early diagnosis and analysis of several diseases like cancer, diabetes, and cardiovascular diseases.
3. Nucleic acid-based biosensors - These are based on the complementarity between the two strands of DNA. A target sequence is used in these biosensors which interacts with a complementary sequence and hence immobilizes it on the biosensor.
4. Cell-based biosensors - Cells are sensitive to their environment and hence can be used to measure the intracellular and extracellular microenvironment conditions. So, the mechanism of these biosensors is to produce a response from the interaction between the cell and the stimuli which is then converted into a signal by the transducer. Researchers in the field of synthetic biology for a long time now have been trying to utilize biological systems to solve problems in areas of medicine, manufacturing and agriculture. The use of cell-based biosensors has helped to solve some of these problems like- Detecting stressful conditions, toxicity, monitoring the effect of drug treatment. Also, microalgae are being used to detect the herbicide concentration in aquatic environments.
All these bioreceptors come with their own set of challenges like use of antibodies as bioreceptors has certain disadvantages: they have limited stability; they are expensive, and they have high molecular weight. But several advancements have taken place in the production of biosensors to combat these problems like use of the domains of antibodies as bioreceptors or engineering small protein scaffolds that have the desired biophysical properties and this has led to more widespread application of these devices. Recent research has utilized biosensors for imaging tests for detection of metastasis of cancer and these techniques have several advantages: they require a smaller sample size; they are rapid and have sensitivity and specificity towards the analyte. According to recent literature they are also being utilized to monitor neural activity and detection of dopamine.
With more advances in Synbio, the uses and development of biosensors are very likely to reach new horizons.