Biosensors emerged as an important technology that has gained much attention in different fields of study. Biosensor is "a self-contained analytical device that combines the biological component with a physicochemical component for the detection of an analyte of biological importance." (Hasan et al. 2014). Perumal & Hashim (2013) defined it according to IUPAC recommendation of 1999, which states that a biosensor is, "an independently integrated receptor transducer device, which is capable of providing selective quantitative or semi-quantitative analytical information using a biological recognition element."The application of nanobiotechnology in the production of biosensors and various other applications is one of the most revolutionary trends in this field. Nanotechnology works as the technology at the nano-scale and has the capability of completely revolutionizing the field of biosensors and opening up a whole lot of opportunities in this field. The integration of nanobiotechnology into biosensors help to create lab-on-chip devices and a lot of other amazing devices that can be applied in a number of interesting fields. Many researches are currently being carried out in the field of biosensors. Hasan et al. (2014) outlined that the industry is now having worth billions of dollars. The biosensor products find application in a number of industries including medical diagnostics, pharmaceutical industries and so forth. However, it still has wider areas of application and continues to evolve with the advancement in technology.
Biosensors comprise of three components that include a detector, a transducer, and a signal processing system. The detector is used to detect the stimulus, and the transducer is used in converting the stimulus to an output signal. While a signal processing system processes the output signal in order to present it in an appropriate and readable format. Hasan (2013) classified biosensors into two types based on their sensing components or the transducer components. Based on their sensing components, biosensors can be classified as catalytic type that includes enzymes, organelles, cells, microbes, tissues. Second type is termed as affinity type that includes antibodies, receptors, and nucleic acids. However, based on their bio-transducer components, biosensors can be classified as electrochemical, optical, acoustic and calorimetric types. The Figure1 is presenting schematic sequence of a biosensor.
Figure 1: Schematic diagram of a biosensor; (Adapted from Gouvêa, 2014)
Biosensors are most widely used in the medical fields. In fact, they have vast areas of applications in the field. These applications include in pharmaceuticals, monitoring the progression of diseases, tissue engineering, and tracking diabetes, cancer and so forth. Gouvêa (2014) pointed out that the biosensors are mostly used in the medical industry because of their fast response time, user-friendly features, cost effectiveness and suitability for mass production. He further stated that biosensors combine approaches from different fields including nanotechnology, chemistry as well as the medical sciences.
In the context of cancer diagnosis, the immense importance of biosensors becomes even more apparent. Bohunicky & Mousa (2010) pointed out that biosensors are designed to detect a given biological analyte. They do so by converting a biological entity such as protein, RNA, and DNA into an electrical signal. This signal can be detected and analyzed. The operational process of a biosensor is represented in figure 1. This is applied in the diagnosis of cancer and also in tracing diabetes. To track the growth of cancerous cells and cancer treatment procedures, biosensors simply monitor the cancer biomarkers which are simply tumor biomarkers. National Cancer Institute explained that a biomarker is a biological molecule which could be found in blood, body tissues and fluids. It shows the occurrence of abnormal process, disease or condition (Bohunicky & Mousa, 2010; Jewett & Patolsky, 2013)). Detecting the presence of tumor, whether it is cancerous or benign, and the effectiveness of the treatment process in eliminating the cancerous cell is simple with biosensors. Biosensors simply leverage the cancer biomarkers to measure the levels of certain proteins secreted or expressed by tumor cells.
Likely, the similar processes occur in monitoring the blood glucose levels in diabetics and detecting pathogens. Vashist et al. (2012) pointed out that biosensors are used for electrochemical sensing for glucose monitoring. Apart from that, that can also be used for the detection of galactose, fructose, neurochemicals, neurotransmitters, amino acids, immunoglobulin, streptavidin, insulin, gonadotropin, and so forth. According to Hasan et al. (2014), there are lots of biosensing approaches provided for glucose monitoring. Examples include electrochemical biosensors used for glucose oxidase or glucose dehydrogenase detection from blood to interstitial fluids. Moreover, optical biosensors for glucose detection using inactive apoenzymes, receptors, and binding proteins fall into this category. Nanobiosensors hold great prospect when it comes to glucose monitoring. The similar technique employed in glucose monitoring having the metabolism process in the cell of engineering tissues in real time (Hasan. et al. 2014; add ref). This finds great usefulness in the fabrication, proliferation and growth of such engineering tissues. In these cases, the metabolism of the cell can be ascertained by their consumption of glucose.
Needless to say, nanotechnology has a great role to play in biosensing technology. Much of the limitations faced by biosensors today can be effectively addressed by nanotechnology. With the application of nanobiotechnology to biosensors in the monitoring of glucose, effectiveness can be ensured. It is imperative to consider that nanotechnology is an all-encompassing technology. In fact, it encompasses different fields of study including physics, medicine, chemistry and so forth (“Nanotechnology.", 2009). The broadness of this technology is the major reason, why it finds usefulness in different fields of study, including biosensors. In order to understand the significance of nanotechnology regarding biosensors, it would be imperative to review, what nanotechnology is all about, its application, benefits, usefulness and otherwise.
Nanoscale can make measurements at the same scales as the basic function of nature. Literary, this scale falls below 100 nm and are, therefore, atomic or molecular scale. In other words, nanotechnology can be defined as technology at the nanoscale or molecular scale, between 0.1 nm to 100 nm. The reason of its importance in the measurement at such small scale is because of the amazing qualities and characteristics materials that display at such scale. Nanotechnology is widely applied in medicine and healthcare; energy production and conservation; electronics, sensors, and computers; security; environmental cleanup; defense and others. Their application in biosensors is remarkable. Nanotechnology leverages addictive manufacturing process and employs tools like transmission electron microscope (TEM), atomic force microscope (AFM) and scanning tunneling microscope (STM) in the manufacturing process. The technology is so much effective that it can be used in manipulating atoms while such manipulation temperature plays a very vital role (Nanotechnolgy, 2009).
The concept of nanotechnology was discovered Richard P. Feynman, who pointed out the possibility of building components at the nanoscale having unimaginable characteristics (LBB, 2009). Nanotechnology, being a multifarious field, can be widely classified depending on their various fields of applications. This leads to the concept of nanobiotechnology that is defined by LBB, (2009) as a field that combines some of the emerging life science applications of nanotechnology and nanoscience. In addition, the technology has to do with the design of new devices and materials which have excellent specificity of biological molecules, cells, and enzymes. They also have wide application areas including the development of innovative biomaterials and sensors which depend on the conformational changes and also the tagging of cells and macromolecules. They can also be exercised in the production of devices, materials and particles which can be used in the delivery of drugs or therapeutic purposes (LBB, 2009). A wide range of application of nanobiosensors is illustrated in figure 2.
Figure 2: Classification of focused fields for Nanobiosensors. Adopted from nanoinstitute.utah.edu/static-content/nanoinstitute/files/images/fields-of-focus-510-b.gif
Of course, conventional biosensors are quite effective and can be largely used for so many purposes. However, Rai, Acharya & Dey (2012) stated that effective and efficient nanobiosensor that has miniature structure in comparison to conventional biosensors can be produced when nanotechnology is employed in the production process. Indeed, nanobiosensors are more effective than conventional biosensors in a number of ways. The benefits of nanobiosensors over conventional biosensors include nanobiosensors that are extremely. Therefore, they can detect single virus particles or extremely low concentration of a substance that could cause a grave harm. Nanobiotechnology has been described as technology at the nanoscale. It functions with amazing efficiency at such scale that cannot be achieved in a conventional sensor (Rai et al., 2012). Thus, nanobiosensors can also function at the atomic scale with the highest level of efficiency that ever thought possible.
Nanobiosensor also has some demerits and usually, these demerits are due to the limitations in the present technology. A lot of researches are currently being carried out to find a solution and also improve it accordingly. Firstly, the ultra-sensitivity of nanobiosensors makes them very prone to errors. A number of researches and studies are already being carried out to find a useful solution to this downside. Furthermore, nanobiosensors are still in their infancy stage, and this makes them highly limited. With improved technology, nanobiosensors would be able to meet up with the needs in the industry.
The application of nanobiotechnology in biosensor is wide and far reaching. It crisscrosses every aspect of biosensors and holds great promises for the future. This is because nanobiotechnology based biosensors hold the features that can be reproduced in the biosensors when nanotechnology is used in the production process. Tothill (2011) also pointed out that there are wide applications of nanobiotechnology in biosensors. These applications range from its use in transducer device, the label, and the running systems as well as the recognition ligand.
Nanobiotechnology offers an excellent advantage to biosensors and therefore makes them unique when used in building this innovation. Some of the advantages have been discussed above, and the overall benefit of using such excellent device in building biosensors is increase in sensitivity. With the increase in sensitivity, the biosensors will be much more effective than conventional biosensors. In addition, the high surface area to volume ratio of the biosensors produced via nanotechnology makes single molecule detection easier. This is of great importance when using biosensors for the monitoring of toxins. Toxin monitoring is a very important field of biosensors that is greatly enhanced and made effective with the use of nanobiotechnology.
Vashist (2012) reported that a number of nanomaterials have been used for biosensors and diagnostics in the last decades. Examples of such nanomaterials include carbon nanotubes quantum dots (QDs), nanoparticles (NPs), nanocomposites and graphene. It is important to take a look at these nanomaterials and their features and usage. This will help to understand the essential features of nanotechnology-based biosensors and diagnostics (NBBD). With nanotechnology-based biosensing, disease diagnosis will become much more effective. This is because they give more accurate information with respect to physiology and also help in ensuring early disease diagnosis. In addition, nanotechnology-based biosensors help in the monitoring of the effectiveness of treatment processes. The treatment can be monitored rapidly and accurately to monitor the progress of the treatment process. For instance, nanoparticles are used in boosting pharmacokinetics and bioavailability. This simply means that the nanoparticles carry the drugs to the direct or specific site of the disease. They do this by making sure that healthy tissues are avoided. As a result of this, treatment dose can be reduced and therefore improving the effectiveness of the treatment process. QDs are also widely used because of their excellent properties such as high photochemical stability, broad excitation, negligible photobleaching and so forth. Because of their excellent features, these are widely used as an excellent alternative to fluorophores. Thus, they serve effectively in building optical biosensors for the detection of ions, organic compounds and pharmaceutical analytes. In fact, all the nanotechnology-based biosensors and diagnostics serve great purposes because of their exceptional features.
Rai et al. (2012) identified the characteristics of an ideal nanobiosensor. This type of biosensor exhibit excellent and interesting characteristics as an ideal nanobiosensor should be able to make a distinction between analytes and non-analytes. In other words, a nanobiosensor should be very specific for analyzes purposes. Of course, analyzes are very integral and essential for a biosensor because they provide a core for their operation. Additionally, nanobiosensors should be stable under storage conditions; physical factors like pH, temperature and stirring should not determine the specific interaction between the analytes in a nanobiosensor. An ideal nanobiosensor should have minimal reaction time having precision as well as reproducible, accurate and linear responses over the useful analytical range. The biosensor should be completely noise-free. The size is another important characteristic of an ideal nanobiosensor; the biosensor should be tiny, non-toxic biocompatible and non-antigenic. Lastly, cost is an important parameter to consider while selecting a biosensor. An ideal nanobiosensor should be cheap and portable. In addition, such biosensors should have user-friendly features.
Nanobiosensors can be classified into various types. These include mechanical nanobiosensors, optical nanobiosensors, nanowire biosensors, ion channel switch biosensor technologies, electrical nanobiosensors, viral nanobiosensors, PEBBLE nanobiosensors, nanoshell biosensors (Rai et al., 2012).These respective types of nanobiosensors have their various operational techniques. For instance, an optical nanobiosensor depends on “the arrangement of optics where light beam is circulated in a closed path and the change is recorded in a resonant frequency when the analyte binds to the resonator." (Rai et al., 2012, p: 318).
Gooding (2011) pointed out that one of the two major areas where nanotechnology has significantly revolutionized biosensors in the recent years is associated with the advancement in nanofabrication of biosensing interfaces. This has developed a long way to accord molecular level control over the fabrication of biosensing interfaces. This is effectively achieved with the rise in self-assembled monolayers (SAMs). The self-assembled monolayers give way to the production of top notch and high-performance biosensors. They also ensure the better transduction mechanism that is developed for biosensors. This give room to greater sensitivity and selectiveness and in some cases, both qualities are ensured in the biosensor produced and the result is optimized effectiveness for the biosensor. Many studies have been conducted to develop biosensors that demonstrate short response time. Such response time is important to ensure the faster processes achievement. For instance, this is important in monitoring of diabetes, cancer and pharmacokinetics activities in the body (Tanaka & Chujo, 2014). Advancement in nanobiosensing ensures that the biosensors produced are compatible with in vivo biosensing processes.
The protein assemblies are integral elements related to bacteria, viruses, eukaryotic cells at point of action of microorganisms. Nanobiotechnology holds ability to exploit these structures by formation of new functional elements. Howorka (2011) explained the basic principles of these natural protein assemblages and highlighted current development to produce biomaterials. These biomaterials have tremendous applications in biocatalysis, materials science, and vaccine development. According to Haruyam (2003), signaling among cells have integrated relationship having slight space and high communication speed. As a matter of fact, cells communicate physical as well as chemical signaling in a living system. The characteristics of the cell encompass development of protein and particular compounds that consequently facilitates organs and tissues. These cellular responses are essential parameters to achieve information regarding medicines effectiveness with safety. Nanobiotechnology facilitates in developing techniques that can be integrated on chip with higher sensitivity for biosensing of cellular activities. Nanotechnology provided new combinations with effective methods that resolved the existing issues related to bio-analytics as well as sensitivity and resolution with the help of interfacing (Haruyam, 2003).
An interesting application of biosensors in the recent years is in the taste cell and receptor-based biosensors. Such biosensors have gained promise for their use in chemical sensing and researches are also being carried out taste signal transduction mechanisms. Wu et al. (2014) mentioned "taste cells and receptors can recognize the specific chemical signal presented by various taste substances offering unique performance characteristics which cannot be achieved by current artificial devices." (Wu et al., 2014, p: 75). Taste cells and receptors are observed as one of the best materials for the development of chemical biosensors. The major challenge here is in the development of a functional taste cell and receptor which will meet the required needs. This can be easily achieved by coupling taste cells and receptors with the right transducers and hence develop chemical biosensors that would meet the required needs. Figure 3 is illustrating a comprehensive taste sensing mechanism.
Figure 3: Flow Chart for Taste Sensing (Source adopted: http://www.mdpi.com/1424-8220/10/4/3411/htm
Furthermore, it is imperative to consider that the future of taste cell and receptor-based biosensors depends heavily on nanobiotechnology. Wu et al. (2014) mentioned that nanotechnology and microfabrication has contributed immensely in the development of taste cell and receptor-based biosensors. It makes possible to develop biosensors that consists of the sensor array and has multiple types of taste cells and receptor. In addition, such biosensors would have the capability of rapid, multiplexed and top notch analysis on miniature platforms.
Nanotechnology has a lot to do in different fields of biosensing. Solanki, Kim & Lee (2008) showed that the nanobiotechnology has to do innovations in regenerative medicine. Biological scientists believe that lots of issues in regenerative medicines can be effectively addressed with the nanobiotechnology. The field of biotechnological studies has been greatly enhanced with the nanobiotechnology, and more is being expected in the future. Nanobiotechnology can be effectively employed in rationally engineering natural protein assemblies and lots of other aspects of life.
Conclusively, the use of nanobiotechnology and nanotechnology in biosensors holds great prospect in the future. Lab-on-a-chip devices and platforms are good examples of such devices that are expected to revolutionize this field. Duval, González-Guerrero & Lechuga (2012) revealed that lab-on-a-chip devices are devices that one can have in the palm of the hand, and they would be able to deliver instant diagnostics of the status of health. The report stated that such devices could become possible very soon with the recent advancement in the field of nanobiosensor. Another interesting trend in this field is silicon photonic biosensors that are excellent devices for point-of-care purposes and healthcare diagnostics (Tanaka & Chujo, 2014). As a matter of fact, these devices could be employed towards excellent applications. Tanaka & Chujo (2014) reviewed the role of nanoparticles in nanobiotechnology and reported that material properties can be evaluated for chemical structures having size equivalent to nanoparticles. The silica nanoparticles have capability to play its role for NMR signals and developing block for fabrication of bio-material. In addition, nanobiotechnology resolved the issues related to non-linear optics with the help of advanced materials having unique functional characteristics (Tanaka & Chujo, 2014).
Future advances in biosensors would provide room to top notch and real portable LOC devices which have been a great challenge in the present time. Although LOC platform based on nanophotonic sensors has been developed as shown in figure 4. But as a matter of fact, a fully operative LOC platform with on-chip detection has not yet been achieved effectively. The future holds great for the advancement in the sensor chip such as integrated interferometric transducers and so forth. Nanotechnology is expected to transform the application and use of biosensors as a result of the improved qualities it accords sensors.
Figure 4: LOC platform based on nanophotonic sensors, Source Adopted: Duval et al., 2012
Nanobiotechnology and biosensors have achieved a remarkable milestone in the field of medical. For instance, with the use of nanobiosenors in diabetes monitoring much more efficiency can be achieved. Also, another trend in this field that is of great interest is the pharmacokinetics and bioavailability effects of nanobiosensors that can enhance the effectiveness of drugs and substantially reduce treatment dose.
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