BT505 Handouts by VUBuddy

BT505: Biosensors

Introduction to biosensors

A biosensor is a device that measures biological or chemical reactions by generating signals proportional to the concentration of an analyte in the reaction. Biosensors are employed in applications such as disease monitoring, drug discovery, and detection of pollutants, disease-causing micro-organisms and markers that are indicators of a disease in bodily fluids (blood, urine, saliva, sweat). Analyte: A substance of interest that needs detection. For instance, glucose is an ‘analyte’ in a biosensor designed to detect glucose.

Features of a biosensor

There are certain static and dynamic attributes that every biosensor possesses. The optimisation of these properties is reflected on 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 immobilised 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 bioreceptors.

Reproducibility

Reproducibility is the ability of the biosensor to generate identical responses for a duplicated experimental set-up. The reproducibility is characterised 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 meas-ured 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 affects 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.

Components of biosensor

Bioreceptor: A molecule that specifically recognises 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 signalisation. 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.

Micro-Electro-Mechanical Systems, or MEMS, is a technology that in its most general form can be defined as miniaturized mechanical and electro-mechanical elements (i.e., devices and structures) that are made using the techniques of microfabrication. The critical physical dimensions of MEMS devices can vary from well below one micron on the lower end of the dimensional spectrum, all the way to several millimeters. Likewise, the types of MEMS devices can vary from relatively simple structures having no moving elements, to extremely complex electromechanical systems with multiple moving elements under the control of integrated microelectronics. The one main criterion of MEMS is that there are at least some elements having some sort of mechanical functionality whether or not these elements can move. The term used to define MEMS varies in different parts of the world. In the United States they are predominantly called MEMS, while in some other parts of the world they are called “Microsystems Technology” or “micromachined devices”.

While the functional elements of MEMS are miniaturized structures, sensors, actuators, and microelectronics, the most notable (and perhaps most interesting) elements are the microsensors and microactuators. Microsensors and microactuators are appropriately categorized as “transducers”, which are defined as devices that convert energy from one form to another. In the case of microsensors, the device typically converts a measured mechanical signal into an electrical signal.