Introduction: What is Biosensor?

A biosensor is a device that detects biological or chemical processes by generating signals proportional to an analyte concentration in the reaction. Biosensors are used in applications such as illness monitoring, drug discovery, and the detection of contaminants, disease-causing microorganisms, and disease markers in bodily fluids (blood, urine, saliva, and sweat).

Type of Biosensor

Physical Biosensor

In conditions of classification, physical biosensors are the most fundamental as well as broadly used sensors. The main ideas behind this categorization also happen from inspecting the human minds. As the general working method behind the intelligence of hearing, sight, touch is to react on the exterior physical stimuli, therefore any detecting device that offers a reaction to the physical possessions of the medium was named as a physical biosensor. The physical biosensors are classified into two types, namely piezoelectric biosensors and thermometric biosensors.

Piezoelectric Biosensors

These sensors are a collection of analytical devices which work on a law of “affinity interaction recording”. The platform of piezoelectric is a sensor element that works on the law of oscillations transform due to a collection jump on the surface of a piezoelectric crystal. In this analysis, biosensors having their modified surface with an antigen or antibody, a molecularly stamped polymer, and heritable information. The declared detection parts are normally united by using nanoparticles.

Thermometric Biosensor

There are various types of biological reactions which are connected with the invention of heat, and this makes the base of thermometric biosensors. These sensors are usually named thermal biosensors. Thermometric-biosensor is used to measure or estimate serum cholesterol. As cholesterol obtains oxidized through the enzyme cholesterol oxidize, then the heat will be produced which can be calculated. Similarly, assessments of glucose, urea, uric acid, and penicillin G can be done with these biosensors.

Optical Biosensor

The Optical biosensor is a device that uses an optical measurement principle. They use fiber optics as well as optoelectronic transducers. The term optrode represents a compression of the two terms optical & electrode. These sensors mainly involve antibodies and enzymes like the transducing elements.

Optical biosensors permit a secure non-electrical, inaccessible sensing of equipment. An extra benefit is that these frequently do not need reference sensors, because the comparative signal can be produced by using a similar light source to the sampling sensor. The optical biosensors are classified into two types' namely direct optical detection biosensors and labeled optical detection biosensors.

Wearable Biosensors

The wearable biosensor is a digital device, used to wear on the human body in different wearable systems like smartwatches, smart shirts, tattoos which allows the levels of blood glucose, BP, the rate of heartbeat, etc

Nowadays, we can notice that these sensors are carrying out a signal of improvement to the world. Their better use and ease can give an original level of experience into a patient’s real-time fitness status. This data accessibility will let superior clinical choices and will affect enhanced health results and extra capable use of health systems.

For human beings, these sensors may assist in premature recognition of health actions and prevention of hospitalization. The possibility of these sensors to reduce hospital stays and re-admissions will definitely attract positive awareness in the upcoming future. As well, investigate information says that WBS will certainly carry cost-effective wearable health equipment to the world.

Enzyme Biosensor

This sensor is one kind of analytical device, used to merge an enzyme using a transducer to generate a signal that is proportional to the concentration of the target analyte. Further, this signal can be amplified, stored, processed for later analysis.

DNA Biosensor

The development of DNA biosensors can be done based on identification techniques of nucleic acid for analysis of simple, rapid & economical testing of genetic & infectious diseases. Also, the exact DNA series detection is important in several areas like food analysis, clinical, environmental, etc. For better detection techniques, SAM & SELEX technologies are used for developing better recognition techniques for DNA Biosensors. Different from antibodies or enzymes, recognition of nucleic acid layers can be willingly created & regenerate for various uses. As compared to normal hybridization, these sensors, as well as gene chips, have many benefits because of their enormous potential for attaining specific data in a simpler, cheaper & faster manner. Further, these sensors have been increased but, the fundamental investigation is still required to enhance the sensor technologies, detecting plans, instrumentation for analytical & procedures.

Immunosensors

Immunosensors were recognized on the truth that antibodies include high affinity to their particular antigens, like the antibodies particularly combine to toxins or pathogens or interact through host immune system’s components. These types of biosensors are based on affinity ligand solid-state devices, where the reaction of immunochemical can be connected to a transducer.

Magnetic Biosensors

These types of sensors are used to gauge changes within magnetically persuaded effects or magnetic properties. These kinds of sensors use crystals or particles of super-paramagnetic otherwise paramagnetic to detect biological communications through measuring changes within magnetic properties like changes within coil inductance, resistance.

Resonant Biosensors

In a resonant biosensor, a transducer like an acoustic wave can be connected through a bio-element. Once the analyte molecule is connected toward the membrane, then the mass of the membrane alters. So, the final change within the mass subsequently alters the transducer’s resonant frequency. After that, the change in frequency can be measured.

Thermal Detection Biosensor

Thermal detection type biosensor uses one of the basic biological reaction properties like heat production or absorption and changes the temperature when the reaction occurs. The designing of this sensor can be done by uniting the molecules of an immobilized enzyme using temperature sensors. Once the analyte & the approaches in contact, then the enzyme’s heat reaction can be measured and & adjusted against the concentration of the analyte. The whole heat generated otherwise absorbed can be proportional toward the molar enthalpy & the total number of molecules within the reaction. The temperature measurement is normally achieved through a thermistor known as enzyme thermistors. Thermistors are ideal in some applications as they are sensitive to thermal changes. Not like other types of transducers, thermal sensors do not require regular recalibration & they are insensible to the properties of electrochemical & optical of the sample. These sensors are used to detect pathogenic & pesticide bacteria.

Characteristics of Biosensor

There are certain static and dynamic attributes that every biosensor possesses. The optimization of these properties is reflected in the performance of the biosensor.

Selectivity

Selectivity is perhaps the most important feature of a biosensor.  Selectivity is the ability of a bioreceptor to detect a specific analyte in a sample containing other admixtures and contaminants. The best example of selectivity is depicted by the interaction of an antigen with the antibody. Classically, antibodies act as bioreceptors and are immobilized on the surface of the transducer. A solution (usually a buffer containing salts) containing the antigen is then exposed to the transducer, where antibodies interact only with the antigens. To construct a biosensor, selectivity is the main consideration when choosing bioreceptor.

Reproducibility

Reproducibility is the ability of the biosensor to generate identical responses for a duplicated experimental set-up. The reproducibility is characterized by the precision and accuracy of the transducer and electronics in a biosensor. Precision is the ability of the sensor to provide alike results every time a sample is measured, and accuracy indicates the sensor's capacity to provide a mean value close to the true value when a sample is measured more than once. Reproducible signals provide high reliability and robustness to the inference made on the response of a biosensor.

Stability

Stability is the degree of susceptibility to ambient disturbances in and around the biosensing system. These disturbances can cause a drift in the output signals of a biosensor under measurement. This can cause an error in the measured concentration and can affect the precision and accuracy of the biosensor. Stability is the most crucial feature in applications where a biosensor requires long incubation steps or continuous monitoring. The response of transducers and electronics can be temperature-sensitive, which may influence the stability of a biosensor. Therefore, appropriate tuning of electronics is required to ensure a stable response of the sensor. Another factor that can influence the stability is the affinity of the bioreceptor, which is the degree to which the analyte binds to the bioreceptor.  Bioreceptors with high affinities encourage either strong electrostatic bonding or covalent linkage of the analyte that fortifies the stability of a biosensor. Another factor that impacts the stability of a measurement is the degradation of the bioreceptor over a period of time.

Sensitivity

The minimum amount of analyte that can be detected by a biosensor defines its limit of detection (LOD) or sensitivity. In a number of medical and environmental monitoring applications, a biosensor is required to detect analyte concentration of as low as ng/ml or even fg/ml to confirm the presence of traces of analytes in a sample. For instance, a prostate-specific antigen (PSA) concentration of 4 ng/ml in blood is associated with prostate cancer, for which doctors suggest biopsy tests. Hence, sensitivity is considered to be an important property of a biosensor.

Linearity

Linearity is the attribute that shows the accuracy of the measured response (for a set of measurements with different concentrations of analyte) to a straight line, mathematically represented as y=mc, where c is the concentration of the analyte, y is the output signal, and m is the sensitivity of the biosensor. Linearity of the biosensor can be associated with the resolution of the biosensor and range of analyte concentrations under test. The resolution of the biosensor is defined as the smallest change in the concentration of an analyte that is required to bring a change in the response of the biosensor. Depending on the application, a good resolution is required as most biosensor applications require not only analyte detection but also measurement of concentrations of analyte over a wide working range. Another term associated with linearity is linear range, which is defined as the range of analyte concentrations for which the biosensor response changes linearly with the concentration.

Constituents of Biosensor

Analyte:

A substance of interest that needs detection. For instance, glucose is an ‘analyte’ in a biosensor designed to detect glucose.

Bioreceptor:

A molecule that specifically recognizes the analyte is known as a bioreceptor. Enzymes, cells, aptamers, deoxyribonucleic acid (DNA) and antibodies are some examples of bioreceptors. The process of signal generation (in the form of light, heat, pH, charge or mass change, etc.) upon interaction of the bioreceptor with the analyte is termed bio-recognition.

Transducer:

The transducer is an element that converts one form of energy into another. In a biosensor, the role of the transducer is to convert the bio-recognition event into a measurable signal. This process of energy conversion is known as signalization. Most transducers produce either optical or electrical signals that are usually proportional to the amount of analyte–bioreceptor interactions.

Electronics:

This is the part of a biosensor that processes the transduced signal and prepares it for display. It consists of complex electronic circuitry that performs signal conditioning such as amplification and conversion of signals from analogue into the digital form. The processed signals are then quantified by the display unit of the biosensor.

Display:

The display consists of a user interpretation system such as the liquid crystal display of a computer or a direct printer that generates numbers or curves understandable by the user. This part often consists of a combination of hardware and software that generates results of the biosensor in a user-friendly manner. The output signal on the display can be numeric, graphic, tabular or an image, depending on the requirements of the end user.

History of Biosensor

The first experiment to mark the origin of biosensors was carried out by Leland C. Clark. For his experiment, Clark used platinum (Pt) electrodes to detect oxygen. He placed the enzyme glucose oxidase (GOD) very close to the surface of platinum by trapping it against the electrodes with a piece of dialysis membrane. The enzyme activity was modified according to the surrounding oxygen concentration. Glucose reacts with glucose oxidase (GOD) to give gluconic acid and produces two electrons and two protons, thereby reducing GOD. The reduced GOD, the electrons, protons, and the surrounding oxygen all react to give hydrogen peroxide and oxidized GOD (the original form), therefore making more GOD available for more glucose to react with. The higher the glucose content, the more oxygen is consumed and the lower the glucose content, the more hydrogen peroxide is produced. This means either an increase in hydrogen peroxide or a decrease in oxygen can be measured to give an indication of the glucose concentration.

Application of Biosensor

Food industry

Biosensors have been used extensively in the food industry for quality control and assurance purposes. These include applications in the agricultural field during crop production and also during food processing. Quality control remains a major part of food production and is responsible for the production of healthy food with a prolonged shelf life and also complies with regulations. Biosensors have been used as on-line or at-line quality sensors that make it possible for quality sorting, automation and reduction of production cost and production time. Also, biosensors have been developed to detect particular compounds in foods. These devices detect chemicals or biological agents that contaminate food or might indicate the presence of unwanted substances in food. Moreover, biosensors have been developed for monitoring and estimating cross-contamination of surfaces and food products.

Environment

Environmental pollution has an impact on human health and can therefore compromise the quality of life. Depending on the purpose, sensitive and selective methods are needed for both quantitative and qualitative determination of target analytes. Biosensors have found widespread use in environmental monitoring for the detection of chemical agents, organic pollutants, potentially toxic elements and pathogens that might pose a health hazard. Biosensors such as immunosensors, aptasensors, genosensors and enzymatic biosensors are amongst the most preferred for environmental monitoring. These are known to use antibodies, aptamers, nucleic acids and enzymes as biological receptors. For example, a biosensor was developed to detect pesticides such as organophosphate and carbamate and also monitor their effects on the environment. Biosensors detect pollutants by measuring colour, light, fluorescence, or electric current.

Medical

Most of the biosensors reported in the past years are found to be based on the phenomena of molecular interactions, which are essentially employed in various forms at different scales. In the discipline of medical science, the applications of biosensors are growing rapidly. Some of the applications that have benefited from the emergence of biosensors include cancer detection and monitoring, cardiovascular disease monitoring, and diabetes control. Cancer diagnosis and treatment are of great interest due to the widespread occurrence of the diseases, high death rate, and recurrence after treatment. In medicine, biosensors can be used to monitor blood glucose levels in diabetics, detect pathogens, and diagnose and monitor cancer progression. The use of emerging biosensor technology could be instrumental in early detection of cancer for effective treatment administration. By measuring levels of certain proteins expressed and/or secreted by tumor cells, biosensors can detect the presence of a tumor, whether benign or cancerous, and also give information of whether treatment is effective in reducing or eliminating such cancerous cells.

Cardiovascular diseases, which are the primary cause of death, are still considered as one of the biggest dilemmas the world is facing with about one million people suffering from it. The ability to detect such diseases earlier may result in the reduction of mortality cases. Some of the sensing techniques that have been used herein include immunoaffinity column assay, fluorometric assays, and enzyme-linked immunosorbent assay. However, the above techniques are laborious, and therefore require well-trained and qualified personnel and are time-consuming. Therefore, biosensors are being used for the detection of cardiac markers and early diagnosis. Biosensors have been reported to offer vast advantages over conventional diagnosis assays since they are established on electrical measurements and also employ biochemical molecular recognition elements which gives a desired selectivity with a particular biomarker of interest.

Conclusion:  New Hope

A Sensor to Take Your Breath Away

Early-stage lung cancer, one of the most common and aggressive cancers, kills around 1.4 million people worldwide every year, so the pursuit of new techniques to accurately detect it remains a global challenge. Now, a highly sensitive graphene biosensor has shown potential in electronic nose devices, which analyse the components of vapour mixtures such as breath. Multi-layered graphene can detect biomarkers selectively and sensitively, providing hope that a cheap, reusable, and accurate breath test for early-stage lung cancer could become a reality.

Sensing the Spread

Artificial intelligence could soon be used to predict the spread of melanoma by using microscopic cameras to analyse the appearance and behaviour of cells. The technique, called quantitative live cell histology, was recently presented at the American Society for Cell Biology/EMBO conference. By building a representation of the functional state of individual cells, the technology can predict the likelihood that a stage III melanoma will progress to stage IV. The computer model can also distinguish between cancer cells taken from different patients.

No Time to Waste

A new screening method that uses sensor particles and a urine test could reveal solid organ transplant rejection sooner than ever – and without a needle biopsy. When an organ is rejected, T cells secrete granzyme B, an enzyme that severs amino acid strands in the organ’s cells and triggers apoptosis. Now, intravenously injected nanoparticles that possess the targets of granzyme B’s amino acids can release reporter molecules once rejection begins. These are small enough to pass out of the body and emit a fluorescent signal in urine. After successfully validating the technique in a mouse model, the researchers are now looking to begin human trials.

Real-Time Robot for Reproductive Hormones

Robotic sensor technology that can be used to measure hormones quickly and cheaply could pave the way for the diagnosis of reproductive health issues in real time. Current blood tests that analyse the amount of luteinizing hormone (LH) in patient samples cannot easily account for fluctuation, which is vital for assessing fertility and reproductive disorders. The team behind the Robotic APTamer-enabled Electrochemical Reader (RAPTER) hope to develop the biosensor for hormone monitoring in vivo, giving clinicians a clearer picture of LH pulsatility.

Slipping Through the Net

New estimates indicate that nearly half of childhood cancers worldwide go undiagnosed and untreated. Current records state that around 200,000 new cases of cancer arise annually in children – but there may be almost twice as many. Modelling suggests that undiagnosed cases in Africa, South Central Asia, and the Pacific Islands account for over half of the total. On the other hand, only three percent of total cases remain undiagnosed in North America and Europe. Perhaps most alarming of all, the study estimates that, if no improvements are made, almost three million cases of childhood cancer will be missed between 2015 and 2030.