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Extremely small sensors

Nanosensors are nanoscale devices that measure physical quantities and convert these to signals that can be detected and analyzed. There are several ways 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, most notably in defense, environmental, and healthcare industries. These 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, due to nanomaterial features not present in bulk material that arise at the nanoscale. 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. In addition to their sensitivity and specificity, nanosensors offer significant advantages in cost and response times, making them 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. There are several challenges for nanosensors, including avoiding drift and fouling, 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. 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. As an example of classification, nanosensors that use molecularly imprinted polymers (MIP) can be divided into three categories, which are electrochemical, piezoelectric, or spectroscopic sensors. Electrochemical sensors  induce a change in the electrochemical properties of the sensing material, which includes charge, conductivity, and electric potential. Piezoelectric sensors either convert mechanical force into electric force or vice versa. This force is then transduced into a signal. MIP spectroscopic sensors can be divided into three subcategories, which are chemiluminescent sensors, surface plasmon resonance sensors, and fluorescence sensors. As the name suggests, these sensors produce light based signals in forms of chemiluminescence, resonance, and fluorescence. As described by the examples, the type of change that the sensor detects and type of signal it induces depend on the type of sensor In one case, upon interaction of the analyte with the receptor, the nanoporous transducer had a change in impedance which was determined as the sensor signal. Other examples include electromagnetic or plasmonic nanosensors, spectroscopic nanosensors such as surface enhanced Raman spectroscopy, magnetoelectronic or spintronic nanosensors, and mechanical nanosensors. The measurement can be achieved by using the following methods: binding active nanoparticles to active proteins within the cell, using site directed mutagenesis to produce indicator proteins, allowing for real time measurements, or by creating a nanomaterial (e. g. nanofibers) with attachment sites for the bio receptors. Another type of nanosensor is one that works through a colorimetric basis. Here, the presence of the analyte causes a chemical reaction or morphological alteration for a visible color change to occur. One such application, is that gold nanoparticles can be used for the detection of heavy metals. Many harmful gases can also be detected by a colorimetric change, such as through the commercially available Dräger Tube. These provide an alternative to bulky, lab scale systems, as these can be miniaturized to be used for point of sample devices. For example, many chemicals are regulated by the Environmental Protection Agency and require extensive testing to ensure contaminant levels are within the appropriate limits. Colorimetric nanosensors provide a method for on site determination of many contaminants.

The production method plays a central role in determining the characteristics of the manufactured nanosensor in that the function of nanosensor can be made through controlling the surface of nanoparticles. There are two main approaches in the manufacturing of nanosensors: top down methods, which begin with a pattern generated at a larger scale, and then reduced to microscale. Bottom up methods start with atoms or molecules that build up to nanostructures.

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.

This method consists in using a tension device to stretch the major axis of a fiber while it is heated, to achieve nano sized scales. This method is specially used in optical fiber to develop optical fiber based nanosensors.

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.

Nanoscience as a whole has many potential applications in the defense and military sector including chemical detection, decontamination, and forensics. 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. 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.

Nanosensors can improve various sub areas within food and environment sectors including food processing, agriculture, air and water quality monitoring, and packaging and transport. Due to their sensitivity, as well as their tunability and resulting binding selectivity, nanosensors are very effective and can be designed for a wide variety of environmental applications. Such applications of nanosensors help in a convenient, rapid, and ultrasensitive assessment of many types of environmental pollutants. 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. Many carbon nanotube based sensors are designed as field effect transistors, taking advantage of their sensitivity. The electrical conductivity of these nanotubes will change due to charge transfer and chemical doping by other molecules, enabling their detection. To enhance their selectivity, many of these involve a system by which nanosensors are built to have a specific pocket for another molecule. 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. Some of these have been designed as field effect transistors, while others take advantage of optical sensing capabilities. Selective analyte binding is detected through spectral shift or fluorescence modulation. 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. These take advantage of the localized surface plasmon resonance (LSPR) that arises at the nanoscale, which results in wavelength specific absorption. This LSPR spectrum is particularly sensitive, and its dependence on nanoparticle size and environment can be used in various ways to design optical sensors. To take advantage of the LSPR spectrum shift that occurs when molecules bind to the nanoparticle, their surfaces can be functionalized to dictate which molecules will bind and trigger a response. For environmental applications, quantum dot surfaces can be modified with antibodies that bind specifically to microorganisms or other pollutants. Spectroscopy can then be used to observe and quantify this spectrum shift, enabling precise detection, potentially on the order of molecules. Another potential implementation takes advantage of the size dependence of the LSPR spectrum to achieve ion sensing. In one study, Liu et al. functionalized gold nanoparticles with a Pb2+ sensitive enzyme to produce a lead sensor. Generally, the gold nanoparticles would aggregate as they approached each other, and the change in size would result in a color change. Interactions between the enzyme and Pb2+ ions would inhibit this aggregation, and thus the presence of ions could be detected. 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.

Nanosensors possess great potential for diagnostic medicine, enabling early identification of disease without reliance on observable symptoms. Ideal nanosensor implementations look to emulate the response of immune cells in the body, incorporating both diagnostic and immune response functionalities, while transmitting data to allow for monitoring of the sensor input and response. However, this model remains a long term goal, and research is currently focused on the immediate diagnostic capabilities of nanosensors. The intracellular implementation of nanosensor synthesized with biodegradable polymers induces signals that enable real time monitoring and thus paves way for advancement in drug delivery and treatment. One example of these 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. 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, or contaminated with bacteria. However, a main drawback is found within the long term use of the implant, where tissue grows on top of the sensors, limiting their ability to compress. This impedes the production of electrical charges, thus shortening the lifetime of these nanosensors, as they use the piezoelectric effect to self power. Similarly to those used to measure atmospheric pollutants, gold particle based nanosensors are used to give an early diagnosis to several types of cancer by detecting volatile organic compounds (VOCs) in breath, as tumor growth is associated with peroxidation of the cell membrane. Another cancer related application, though still in mice probing stage, is the use of peptide coated nanoparticles as activity based sensors to detect lung cancer. The two main advantages of the use of nanoparticles to detect diseases is that it allows early stage detection, as it can detect tumors the size in the order of millimeters. It also provides a cost effective, easy to use, portable, and non invasive diagnostic tool. A recent effort towards advancement in nanosensor technology has employed molecular imprinting, which is a technique used to synthesize polymer matrices that act as a receptor in molecular recognition. Analogous to the enzyme substrate lock and key model, molecular imprinting uses template molecules with functional monomers to form polymer matrices with specific shape corresponding to its target template molecules, thus increasing the selectivity and affinity of the matrices. This technique has enabled nanosensors to detect chemical species. In the field of biotechnology, molecularly imprinted polymers (MIP) are synthesized receptors that have shown promising, cost effective alternatives to natural antibodies in that they are engineered to have high selectivity and affinity. For example, an experiment with MI sensor containing nanotips with non conductive polyphenol nano coating (PPn coating) showed selective detection of E7 protein and thus demonstrated potential use of these nanosensors in detection and diagnosis of human papillomavirus, other human pathogens, and toxins. As shown above, nanosensors with molecular imprinting technique are capable of selectively detecting ultrasensitive chemical species in that by artificially modifying the polymer matrices, molecular imprinting increases the affinity and selectivity. In order to develop smart health care with nanosensors, a network of nanosensors, often called nanonetwork, need to be established to overcome the size and power limitations of individual nanosensors. Nanonetworks not only mitigates the existing challenges but also provides numerous improvements. Cell level resolution of nanosensors will enable treatments to eliminate side effects, enable continuous monitoring and reporting of patients’ conditions. Nanonetworks require further study in that nanosensors are different from traditional sensors. The most common mechanism of sensor networks are through electromagnetic communications. However, the current paradigm is not applicable to nanodevices due to their low range and power. Optical signal transduction has been suggested as an alternative to the classical electromagnetic telemetry and has monitoring applications in human bodies. Other suggested mechanisms include bioinspired molecular communications, wired and wireless active transport in molecular communications, Forster energy transfer, and more. It is crucial to build an efficient nanonetwork so that it can be applied in fields such as medical implants, body area networks (BAN), internet of nano things (IoNT), drug delivery and more. With an adept nanonetwork, bio implantable nanodevices can provide higher accuracy, resolution, and safety compared to macroscale implants. Body area networks (BAN) enable sensors and actuators to collect physical and physiological data from the human body to better anticipate any diseases, which will thus facilitate the treatment. Potential applications of BAN include cardiovascular disease monitoring, insulin management, artificial vision and hearing, and hormonal therapy management. The Internet of Bio Nano Things refers to networks of nanodevices that can be accessed by the internet. Development of IoBNT has paved the way to new treatments and diagnostic techniques. Nanonetworks may also help drug delivery by increasing localization and circulation time of drugs. 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.