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Nanosensors are nanoscale devices that measure physical quantities and convert those quantities to signals that can be detected and analyzed. There are several ways being proposed today to make nanosensors; these include top-down lithography, bottom-up assembly, and molecular self-assembly. There are different types of nanosensors in the market and in development for various applications. Though all sensors measure different things, sensors share the same basic workflow: a selective binding of an analyte, signal generation from the interaction of the nanosensor with the bio-element, and processing of the signal into useful metrics.
Nanomaterials-based sensors have several benefits in sensitivity and specificity over sensors made from traditional materials. Nanosensors can have increased specificity because they operate at a similar scale as natural biological processes, allowing functionalization with chemical and biological molecules, with recognition events that cause detectable physical changes. Enhancements in sensitivity stem from the high surface-to-volume ratio of nanomaterials, as well as novel physical properties of nanomaterials that can be used as the basis for detection, including nanophotonics. Nanosensors can also potentially be integrated with nanoelectronics to add native processing capability to the nanosensor.:4–10
In addition to their sensitivity and specificity, nanosensors offer significant advantages in cost and response times, which makes nanosensors suitable for high-throughput applications. Nanosensors provide real-time monitoring compared to traditional detection methods such as chromatography and spectroscopy. These traditional methods may take days to weeks to obtain results and often require investment in capital costs as well as time for sample preparation.
One-dimensional nanomaterials such as nanowires and nanotubes are well suited for use in nanosensors, as compared to bulk or thin-film planar devices. They can function both as transducers and wires to transmit the signal. Their high surface area can cause large signal changes upon binding of an analyte. Their small size can enable extensive multiplexing of individually addressable sensor units in a small device. Their operation is also "label free" in the sense of not requiring fluorescent or radioactive labels on the analytes.:12–26
There are several challenges for nanosensors, including avoiding fouling and drift, developing reproducible calibration methods, applying preconcentration and separation methods to attain a proper analyte concentration that avoids saturation, and integrating the nanosensor with other elements of a sensor package in a reliable manufacturable manner.:4–10 Because nanosensors are a relatively new technology, there are many unanswered questions regarding nanotoxicology which currently limits their application in biological systems. Some nanosensors may impact cell metabolism and homeostasis, changing cellular molecular profiles and making it difficult to separate sensor-induced artifacts from fundamental biological phenomena.
Potential applications for nanosensors include medicine, detection of contaminants and pathogens, and monitoring manufacturing processes and transportation systems.:4–10 By measuring changes in physical properties (volume, concentration, displacement and velocity, gravitational, electrical, and magnetic forces, pressure, or temperature) nanosensors may be able to distinguish between and recognize certain cells at the molecular level in order to deliver medicine or monitor development to specific places in the body. The type of signal transduction defines the major classification system for nanosensors. Some of the main types of nanosensor readouts include optical, mechanical, vibrational, or electromagnetic.
Mechanisms of operation
There are many mechanisms by which a recognition event can be transduced into a measurable signal. Electrochemical nanosensors are based on detecting a resistance change in the nanomaterial upon binding of an analyte, due to changes in scattering or to the depletion or accumulation of charge carriers. One possibility is to use nanowires such as carbon nanotubes, conductive polymers, or metal oxide nanowires as gates in field-effect transistors, although as of 2009 they had not yet been demonstrated in real-world conditions.:12–26 Chemical nanosensors contain a chemical recognition system (receptor) and a physiochemical transducer, in which the receptor interacts with analyte to produce electrical signals. Other examples include electromagnetic or plasmonic nanosensors, spectroscopic nanosensors such as surface-enhanced Raman spectroscopy, magnetoelectronic or spintronic nanosensors, and mechanical nanosensors.:12–26
Photonic devices can also be used as nanosensors to quantify concentrations of clinically relevant samples. A principle of operation of these sensors is based on the chemical modulation of a hydrogel film volume that incorporates a Bragg grating. As the hydrogel swells or shrinks upon chemical stimulation, the Bragg grating changes color and diffracts light at different wavelengths. The diffracted light can be correlated with the concentration of a target analyte.
There are currently several hypothesized ways to produce nanosensors. Top-down lithography is the manner in which most integrated circuits are now made. It involves starting out with a larger block of some material and carving out the desired form. These carved out devices, notably put to use in specific microelectromechanical systems used as microsensors, generally only reach the micro size, but the most recent of these have begun to incorporate nanosized components.
Another way to produce nanosensors is through the bottom-up method, which involves assembling the sensors out of even more minuscule components, most likely individual atoms or molecules. This would involve moving atoms of a particular substance one by one into particular positions which, though it has been achieved in laboratory tests using tools such as atomic force microscopes, is still a significant difficulty, especially to do en masse, both for logistic reasons as well as economic ones. Most likely, this process would be used mainly for building starter molecules for self-assembling sensors.
The third way, which promises far faster results, involves self-assembly, or "growing" particular nanostructures to be used as sensors. This most often entails an already complete set of components that would automatically assemble themselves into a finished product. Accurately being able to reproduce this effect for a desired sensor in a laboratory would imply that scientists could manufacture nanosensors much more quickly and potentially far more cheaply by letting numerous molecules assemble themselves with little or no outside influence, rather than having to manually assemble each sensor.
One of the first working examples of a synthetic nanosensor was built by researchers at the Georgia Institute of Technology in 1999. It involved attaching a single particle onto the end of a carbon nanotube and measuring the vibrational frequency of the nanotube both with and without the particle. The discrepancy between the two frequencies allowed the researchers to measure the mass of the attached particle.
Since then, increasing amounts of research have gone into nanosensors, whereby modern nanosensors have been developed for many applications. Currently, the applications of nanosensors in the market include: healthcare, defense and military, and others such as food, environment, and agriculture.
Defense and military
Nanoscience as a whole has much potential for applications in the defense and military sector. Applications include chemical detection, decontamination, and forensics. However, the primary efforts surrounding nanosensors largely remain in research and development.
Some nanosensors in development for defense applications include nanosensors for the detection of explosives or toxic gases. Such nanosensors work on the principle that gas molecules can be distinguished based on their mass using, for example, piezoelectric sensors. If a gas molecule is adsorbed at the surface of the detector, the resonance frequency of the crystal changes and this can be measured as a change in electrical properties. In addition, field effect transistors, used as potentiometers, can detect toxic gases if their gate is made sensitive to them.
In a similar application, nanosensors can be utilized in military and law enforcement clothing and gear. The Navy Research Laboratory's Institute for Nanoscience has studied quantum dots for application in nanophotonics and identifying biological materials. Nanoparticles layered with polymers and other receptor molecules will change color when contacted by analytes such as toxic gases. This alerts the user that they are in danger. Other projects involve embedding clothing with biometric sensors to relay information regarding the user's health and vitals, which would be useful for monitoring soldiers in combat.
Surprisingly, some of the most challenging aspects in creating nanosensors for defense and military use are political in nature, rather than technical. Many different government agencies must work together to allocate budgets and share information and progress in testing; this can be difficult with such large and complex institutions. In addition, visas and immigration status can become an issue for foreign researchers - as the subject matter is very sensitive, government clearance can sometimes be required. Finally, there are currently not well defined or clear regulations on nanosensor testing or applications in the sensor industry, which contributes to the difficulty of implementation.
Food and the environment
Nanosensors can improve various sub-areas within food and environment sectors including food processing, agriculture, air and water quality monitoring, and packaging and transport. These nanosensors enable rapid analysis of samples and detection of contaminants in food which is especially important for downstream processing and perishable items.
Chemical sensors are useful for analyzing odors from food samples and detecting atmospheric gases. The "electronic nose" was developed in 1988 to determine the quality and freshness of food samples using traditional sensors, but more recently the sensing film has been improved with nanomaterials. A sample is placed in a chamber where volatile compounds become concentrated in the gas phase, whereby the gas is then pumped through the chamber to carry the aroma to the sensor that measures its unique fingerprint. The high surface area to volume ratio of the nanomaterials allows for greater interaction with analytes and the nanosensor's fast response time enables the separation of interfering responses. Chemical sensors, too, have been built using nanotubes to detect various properties of gaseous molecules. Carbon nanotubes have been used to sense ionization of gaseous molecules while nanotubes made out of titanium have been employed to detect atmospheric concentrations of hydrogen at the molecular level. Many of these involve a system by which nanosensors are built to have a specific pocket for another molecule. When that particular molecule, and only that specific molecule, fits into the nanosensor, and light is shone upon the nanosensor, it will reflect different wavelengths of light and, thus, be a different color. In a similar fashion, Flood et al. have shown that supramolecular host–guest chemistry offers quantitative sensing using Raman scattered light as well as SERS.
Other types of nanosensors, including quantum dots and gold nanoparticles, are currently being developed to detect pollutants and toxins in the environment. Quantum dot surfaces can be modified with antibodies that bind specifically to environmental pollutants. Gold nanoparticle-based optical sensors can be used to detect heavy metals very precisely; for example, mercury levels as low as 0.49 nM. This sensing modality takes advantage of fluorescence resonance energy transfer (FRET), in which the presence of metals inhibits the interaction between quantum dots and gold nanoparticles, and quenches the FRET response.
The main challenge associated with using nanosensors in food and the environment is determining their associated toxicity and overall effect on the environment. Currently, there is insufficient knowledge on how the implementation of nanosensors will affect the soil, plants, and humans in the long-term. This is difficult to fully address because nanoparticle toxicity depends heavily on the type, size, and dosage of the particle as well as environmental variables including pH, temperature, and humidity To mitigate potential risk, research is being done to manufacture safe, nontoxic nanomaterials, as part of an overall effort towards green nanotechnology.
One example of nanosensors involves using the fluorescence properties of cadmium selenide quantum dots as sensors to uncover tumors within the body. A downside to the cadmium selenide dots, however, is that they are highly toxic to the body. As a result, researchers are working on developing alternate dots made out of a different, less toxic material while still retaining some of the fluorescence properties. In particular, they have been investigating the particular benefits of zinc sulfide quantum dots which, though they are not quite as fluorescent as cadmium selenide, can be augmented with other metals including manganese and various lanthanide elements. In addition, these newer quantum dots become more fluorescent when they bond to their target cells.
Another application of nanosensors involves using silicon nanowires in IV lines to monitor organ health. The nanowires are sensitive to detect trace biomarkers that diffuse into the IV line through blood which can monitor kidney or organ failure. These nanowires would allow for continuous biomarker measurement, which provides some benefits in terms of temporal sensitivity over traditional biomarker quantification assays such as ELISA.
Nanosensors can also be used to detect contamination in organ implants. The nanosensor is embedded into the implant and detects contamination in the cells surrounding the implant through an electric signal sent to a clinician or healthcare provider. The nanosensor can detect whether the cells are healthy, inflammatory, of contaminated with bacteria.
Currently, there are stringent regulations in place for the development of standards for nanosensors to be used in the medical industry, due to insufficient knowledge of the adverse effects of nanosensors as well as potential cytotoxic effects of nanosensors. Additionally, there can be a high cost of raw materials such as silicon, nanowires, and carbon nanotubes, which prevent commercialization and manufacturing of nanosensors requiring scale-up for implementation. To mitigate the drawback of cost, researchers are looking into manufacturing nanosensors made of more cost-effective materials. There is also a high degree of precision needed to reproducibly manufacture nanosensors, due to their small size and sensitivity to different synthesis techniques, which creates additional technical challenges to be overcome.
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