16 June 2017

Biosensors (Part 3)

Technological comparison of biosensors

Continuation. The beginning of the article is here.

In the previous sections of the article, different types of biosensors and their applications are discussed. This section presents a comparison of biosensors in terms of technology, specificity and detection threshold, linearity range, analysis duration, cost and portability.

Innovations in the field of high-throughput electrochemical sensors aimed at optimizing the detection threshold, analysis duration and portability have ensured the emergence of large-scale consumer markets for inexpensive biosensors used as glucose and pregnancy tests. The latter is based on the use of test strips with mobilized antibodies to human chorionic gonadotropin detected using immunochromatography technology. Immobilization of analytes using polymers and nanomaterials is the key to improving sensitivity and detection threshold. From this point of view, immunochromatographic analysis on test strips allows placing samples in a given place to trigger specific interactions, rather than interactions occurring randomly. Most of the biosensors mentioned above are based on this technology, which actually paved the way for bio-production using contact and contactless formation. The use of nanomaterials such as gold, silver and silicon oxide for bio-production has led to the emergence of new methods. In addition, the application of a polymer coating on such nanomaterials has revolutionized the field of contact electrochemical methods of signal registration. One of the main advantages of this type of electrochemical sensors is the sensitivity and specificity when performing real-time analysis. The limitations in this case are the ability to regenerate or the long-term use of polymers/other materials, but the reduction in cost makes such electrochemical sensors more affordable. Detection of a single analyte using contact signal detection methods has huge advantages, for example, the ability to change the concentration of molecules with high specificity in real time. To improve the specificity and sensitivity in the detection of single molecules, technologies such as resonant transfer of fluorescence energy, resonant transfer of bioluminescence energy, as well as converters based on fluorescence and plasmon resonance were introduced. With simultaneous detection of several analytes, these technologies have limitations due to the imposition of signal emission, however, methods based on resonant energy transfer are often used in such situations, which is very important for clinical diagnosis due to differences in biomarker levels in different patients and with similar pathologies. The use of micro- and nanocantilevers as converters in the bio-production of electrochemical sensors is also more promising for the simultaneous detection of several analytes. Non-contact sensors produced by three-dimensional bioprinting using an inkjet or laser printer also demonstrated good results. However, the necessary costs and adaptable capabilities of these methods have serious limitations. Interestingly, most of these high-throughput biosensors are combined with electrochemical registration methods to fulfill specific purposes. Some of the most noteworthy portable amperometric electrochemical biosensors operating in real time have been developed for the diagnosis of diseases using biological fluids. In general, electrochemical biosensors in combination with bio-production have a low detection threshold for individual analytes during real-time analysis, as well as an affordable price, given the portability of the device.

Optical biosensors represent another important technology in the field of biosensor analysis, based on the use of fiber-optic chemistry. Identification of individual molecules, for example, DNA or peptides, is most effective when using cross-linked hydrogels with a high capacity coefficient and hydrophilic nature. Optical biosensors for measuring the amount of DNA have been developed, which are widely used in biomedicine and criminology. Combinations of biological materials such as enzyme/substrate, antibody/antigen and nucleic acids have revolutionized the technology of optical biosensors. In addition, microorganisms, animal or plant cells, as well as tissue sections can be incorporated into the biosensor system. Recent advances in molecular optoelectronics have led to the possibility of optical biometric recognition systems. Integrated optical technology allows the incorporation of both passive and active optical components into the same substrate for the development of minimized compact recording devices in the production of multiple sensors on a single chip. In this context, high-quality polymers are used to manufacture hybrid systems for optical biosensors. In fact, the technology of optical biosensors has been improved with the help of modern innovations in the field of surface morphology analysis using high-tech electron and atomic force microscopy. Despite this, the detection threshold of optical biosensors has never approached the femto level due to the cost of instrumentation and non-portability of the device. Modern optical technologies using nanomechanical biosensors based on microcantilevers or surface resonance technology have formed the basis of innovative DNA chips, at least for conducting specific and sensitive analysis in real time. The advantages of optical biosensors mainly lie in the high speed of analysis with signal resistance to electrical or magnetic interference, as well as the potential spectrum of information provided. On the other hand, the main disadvantage is the high cost due to certain equipment requirements. Solving other technical problems, such as the complexity of immobilization, especially for bio-production, and the need for sterile conditions, is a critical issue to maximize the benefits of optical biosensors.

Bio-production of medical devices provides the best results in terms of mass production of biosensors. Electrochemical and optical biosensors are the main technological components in the development of high-end biosensors. Serious achievements in the field of micro- and nanoproduction technologies have made it possible to develop mechanical devices with moving parts of nanoscale sizes. The possibility of producing such structures using semiconductor materials processing procedures has combined biophysical and bioengineering principles in the direction of the progress of micro- and nanoelectromechanical biosensors suitable for mass production. Materials based on glass, silicon oxide and quartz are successfully used after labeling with fluorescent agents or gold nanoparticles. Despite the fact that such biosensors have higher accuracy in detecting individual molecules, their low-cost mass production is less realistic. The mass production of sensors is associated with a number of problems, namely, the complexity of stronger binding of agents at the nanoscale during production using microelectronic technologies for high-speed analysis. In this regard, it is worth mentioning the huge potential for the use of semiconductor materials and quantum dot technology. To date, none of the existing biosensor technologies allows simultaneous quantitative analysis of large arrays of samples in real time, however, the introduction of micro- and nanoscale cantilever production technologies can make this a reality.

Another important technical revolution in the field of biosensors was the possibility of creating genetically encoded or synthetic fluorescent biosensors for the analysis of molecular mechanisms of biological processes. Despite the fact that such biosensors have great prospects in the field of detecting individual molecules with measuring the amount of a specific analyte, the methodology of sample preparation and detection is very complex and requires high-tech equipment. From the point of view of biomaterials, biosensors operating on microbiological fuel cells have good characteristics in terms of high sensitivity and selectivity. However, the methods of mass production and genetic engineering required to create a strain of microorganisms are very complex and costly. At the same time, the advantage of microbial biosensors is the possibility of their use as a tool for bioremediation, which is of great importance from the point of view of monitoring the state of the environment. However, the development and release into the environment of such a genetically modified strain of microorganisms, in addition to regulating production costs, must be subject to strict control, comply with ethical requirements, and be regulated by law.

In general, it can be stated that the creation of highly sensitive miniature devices requires the development of various micro- and nanobiosensory platforms involving integrated technologies using electrochemical or optical bioelectronic principles with a combination of biomolecules or biological materials, polymers and nanomaterials.

End: Current research trends, future challenges and limitations of biosensor technology.

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16.06.2017

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