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Types of Biosensors Information

Sensor is a device which detects changes in a physical quantity like temperature, humidity, water flow, intensity of light etc. and converts it into a quantity that can be measured and/or analyzed.Similarly, a Biosensor is a device, which converts a Biological signal into a more useful electrical signal. Biosensor is an analytical device that detects changes in Biological processes and converts them into an electrical signal. The term Biological process can be any biological element or material like enzymes, tissues, microorganisms, cells, acids, etc. So, a Biosensor is a combination of a Biological sensing element and a transducer, which converts the data into electrical signals. Additionally, there will be an electronic circuit which consists of a Signal Conditioning Unit, a Processor or Microcontroller and a Display Unit.The Signal Conditioning unit comprises of an Amplifier and a Filter (usually a Low Pass Filter) circuitry. ^[1]

Principle of Biosensors

The desired biological material is usually in the form of an enzyme. By a process known as Electroenzymatic approach, which is a chemical process of converting the enzymes into corresponding electrical signals (usually current) with the help of a transducer. One of the commonly used Biological response is the oxidation of the enzyme. Oxidation acts as a catalyst and alters the pH of the biological material. The change in pH will directly affect the current carrying capacity of the enzyme, which is once again, in direct relation to the enzyme being measured.Output of the transducer i.e. the current, is a direct representation of the enzyme being measured. The current is generally converted into voltage so that it can be properly analyzed and represented. ^[2]

Working of Biosensors

The combination of biological sensitive element and a transducer will convert the biological material into a corresponding electrical signal. Depending on the type of enzyme, the output of the transducer will be either current or voltage. If the output is voltage, then well and good. But if the output is current, then this current should be converted into equivalent voltage (using an Op-Amp based current to voltage converter) before proceeding further. The output voltage signal is usually very low in amplitude and superimposed on a high frequency noise signal. So, the signal is amplified (using an Op-Amp based Amplifier) and then passed through a Low Pass RC Filter. This process of amplifying and filtering the signal is the job of a Signal Processing Unit or a Signal Conditioning Unit. The output of the signal processing unit is an analog signal that is equivalent to the biological quantity being measured. The analog signal can be displayed directly on an LCD display but usually, this analog signal is passed to a Microcontroller, where the analog signal is converted into digital signal, since it is easy to analyze, process or store a digital signal.

Classification of Biosensors ^[3]

Biosensors are classified into two groups:

1. Based on the Biological Element used in the analysis:

Some of the commonly used biological elements or bio-recognition elements are DNA, enzymes, antibodies, microorganisms, tissues, cell receptors etc.

2. Based on the method of transduction :

most commonly used classification of Biosensors is based on the type of transduction used in the sensor i.e. type of physiochemical resulting from the sensing event.

the biosensors based on method of transduction are again divided into three types:

1. Mass based Biosensors:

The mass-based biosensors, also known as gravimetric biosensors, apply the basic principle of a response to a change in mass. Most gravimetric biosensors use piezoelectric quartz crystals, which can either be in the form of resonating crystals (quartz crystal microbalance, QCM), or as surface acoustic wave (SAW) devices. Since these have ease of use, shorter analysis time, low cost, and the ability to produce label-free measurement, QCM based sensors have been a star in the area of rapid detection of pathogens and toxins for the past few years. Typically, a QCM biosensor consists of an AT-cut quartz crystal wafer in the middle of two metal electrodes, and the resonant frequency of QCM will change according to the mass change at the crystal's surface. The decrease in frequency is proportional to the mass on the sensor. As a result, by combining the QCM devise with highly specific interaction such as antigen-antibody it can enable the direct detection of micro-organisms. SAW based biosensors can detect acoustic waves generated by mass loading on the surface of the piezoelectric crystal via the interdigital transducers (IDT).The IDT allows the acoustic energy to be strongly confined to the surface no matter the thickness of the substrate. The analyte recognition by the immobilized receptors changes the velocity of SAW and produces signal by the driving electronics.

2. Electrochemical Biosensors:

In electrochemical biosensors, ^[4] the biological molecules are coated onto a probing surface. The sensing molecules are held in place with the help of non-interfering membrane. Then, the sensing molecules react appropriately to the compound to be detected and produces an electrical signal proportional to the quantity being measured.Electrochemical biosensors convert analyte recognition to an electronic signal, which exhibits advantages such as simplicity, lower cost, excellent detection limits, and robustness. It also has the ability to analyze small amounts of samples and the output is easy to read-out and process. Electrochemical biosensors mainly use enzymes as the recognition moiety (one of the exceptions is immunosensor utilizing antibody-antigen) because of the enzyme biocatalytic activity and specificity.Electrochemical transducers can be divided into three main categories.First, amperometry, which measures the current caused by the electrochemical oxidation or reduction of an electroactive species. The resulting current is proportional to the analyte concentration. The second one is potentiometry, which measures the potential between two different electrodes when there are no significant current flows between them using a high impedance voltmeter. Potentiometry can present the information about ion activities in electrochemical reactions. Lastly, the conductometry, which measures the analyte's ability to conduct an electrical current between electrodes or reference nodes induced by biorecognition events that change ionic species' concentration. For example, Soldatkin et al. developed a sensor that is highly sensitive to substrate (sucrose) and heavy metal ions, especially to Hg2+ and Ag+, using immobilized enzymes (e.g., invertase, mutarotase, glucose oxidase) to generate signals, caused by the enzymatic reaction inhibition via changes of the medium conductivity.

Electrochemical Biosensors can employ various types of transducers like Potentiometric, Amperometric,Conductometric, Impedimetric etc. converting the chemical information into a measurable electrical signal.

Potentiometric

This type of biosensor provides a logarithmic reply by means of a high energetic range. These biosensors are frequently complete by monitor producing the electrode prototypes lying on a synthetic substrate, covered by a performing polymer with some enzyme is connected.They comprise two electrodes which are enormously responsive and strong. They allow the recognition of analytes on stages before only attainable by HPLC, LC/MS & without exact model preparation. All types of biosensors generally occupy least sample preparation because the biological detecting component is extremely choosy used for the analyte troubled. By the changes of physical and electrochemical the signal will be generated by in the layer of conducting polymer due to modifying happening at the outside of the biosensor. These changes might be credited to ionic force, hydration, pH, and redox responses, the later as the label of enzyme rotating above a substrate. In FETs, the gate terminal has been changed with an antibody or enzyme, can also sense very-low attentions of different analytes because the required of analyte toward the gate terminal make a modify in the drain to source current.

Amperometric

An amperometric biosensor is a self-contained incorporated device based on the amount of the current ensuing from the oxidation offering exact quantitative analytical information. Generally, these Biosensors have reaction times, energetic ranges & sensitivities comparable to the Potentiometric-biosensors. The simple amperometric biosensor in frequent usage includes the “Clark oxygen” electrode.The rule of this biosensor is based on the amount of the flow of current between Counter Electrode and the working which is encouraged by a redox response at the operational electrode. Choosing analyte centers is essential for a wide selection of uses, comprising high-throughput medicine screening, quality control, problem finding and handling, and biological checking.

Conductometric

This type have conductometric transducers consisted of gold interdigitated electrodes were placed on the ceramic support. The transducers were modified with zeolites and MSS, and then the enzymes were adsorbed on the transducer surface. Different methods of zeolite attachment to the transducer surface were used; drop coating with heating to 200°C turned out to be the best one. Nanozeolites beta and L, zeolite L, MSS, and silicalite-1 (80 to 450 nm) were tested as the adsorbents for enzyme urease. The biosensors with all tested particles except zeolite L had good analytical characteristics. Silicalite-1 (450 nm) was also used for adsorption of glucose oxidase, acetylcholinesterase, and butyrylcholinesterase. The glucose and acetylcholine biosensors were successfully created, whereas butyrylcholinesterase was not adsorbed on silicalite-1. The enzyme adsorption on zeolites and MSS is simple, quick, well reproducible, does not require use of toxic compounds, and therefore can be recommended for the development of biosensors when these advantages are especially important.

Impedimetric

The EIS (Electrochemical impedance spectroscopy) is a responsive indicator for a broad range of physical as well as chemical properties. A rising trend towards the expansion of Impedimetric-biosensors is being presently observed. The techniques of Impedimetric have been executed to differentiate the invention of the biosensors as well as to examine the catalyzed responses of enzymes lectins, nucleic acids, receptors, whole cells, and antibodies.

3. Optical based Biosensors:

Optical Fibers play an important role in Optical Biosensors. The optical fibers allow detection of the sensing elements based on the different properties of light like absorption, scattering and fluorescence.The reaction causes changes in either of the above mentioned properties as a result of the change in the refractive index of the interacting surface. For example, if the biological elements are antibodies and are bound with a metal layer, the refractive index of the medium which comes in contact with this layer will be varied. One of the main advantages of using optical biosensors is their non-electrical nature. This allows them to analyze multiple elements on a single layer just by varying the wavelength of the light.

Optical biosensors ^[5] work on the interaction of optical fields with their biorecognition components to achieve their detection purpose. They are one of the most commonly used biosensors because of their sensitivity, specificity, and small footprints. The optical biosensors can generally be divided into two categories: label-free and label-based. Label-free sensing means that the signal is directly generated from the interaction between the sample and the transducer. In the label-based approach, the target analyte has to be tagged with a reporter molecule, which enables the detection via fluorescent, luminescent, or colorimetric signals. Commonly seen optical biosensors includes, fluorescent, surface plasmon resonance (SPR), interferometer, optical waveguild, and ring resonator. The SPR phenomenon occurs at the interface of the two conducting materials (e.g., glass and metal) when polarized light illuminates at a specific angle.36 This will generate a surface plasma wave along the surface. Since the wave is on the boundary of the conductor and the external medium (air, water or vacuum for example), these oscillations are very sensitive to any change of this boundary, such as the absorption of molecules to the conducting surface. By measuring the changes in wavelengths, reflectivity, and angles against time, we can attain the detection result. SPR sensors such as Biacore™ are used in the measuring of antibody-antigen interactions like binding affinities, kinetic rate constants and thermodynamics. The recognition component is immobilized on the sensor chip surface and followed by the injection of the analyte flowing across the surface. The changes in the index of refraction at the surface caused by binding interactions are detected and recorded as resonance units by the sensor. Another type of optical transducer is the ring resonator. When binding with the surface, the absorption of the molecules increases the refractive index, which alters the overall effective index and leads to a shift in the cavity's resonance wavelength. The difference can be determined through a tunable laser source.Flueckiger et al.have developed a sub-wavelength gratings (SWG) ring resonator designed for transverse electric polarized light to enable more sensitive detection over the transverse magnetic ring resonator. The SWG waveguide can minimize the mismatch loss and improve the field overlap of biomolecules on the waveguide's surface by engineering the effective refractive index, which is the ratio of the propagation constant for a given polarization in the direction of propagation in a waveguide structure to the free space propagation constant.

Classification outline Chart

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