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.
Characteristics 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. Zinc oxide nanowire is used for gas sensing applications, given that it exhibits high sensitivity toward low concentration of gas under ambient conditions and can be fabricated easily with low cost.
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. Because nanosensors are a relatively new technology, there are many unanswered questions regarding nanotoxicology, which currently limits their application in biological systems.
Potential applications for nanosensors include medicine, detection of contaminants and pathogens, and monitoring manufacturing processes and transportation systems. 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.Lim, T.-C.; Ramakrishna, S. A Conceptual Review of Nanosensors. http://www.znaturforsch.com/aa/v61a/s61a0402.pdf.
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
Mechanisms of operation There are multiple mechanisms by which a recognition event can be transduced into a measurable signal; generally, these take advantage of the nanomaterial sensitivity and other unique properties to detect a selectively bound analyte.
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. Chemical nanosensors contain a chemical recognition system (receptor) and a physiochemical transducer, in which the receptor interacts with analyte to produce electrical signals.Chemical Sensors. http://nano-bio.ehu.es/files/chemical_sensors1.doc_definitivo.pdf (accessed Dec 6, 2018) In one case,Agnivo Gosai, Brendan Shin Hau Yeah, Marit Nilsen-Hamilton, Pranav Shrotriya, Label free thrombin detection in presence of high concentration of albumin using an aptamer-functionalized nanoporous membrane, Biosensors and Bioelectronics, Volume 126, 2019, Pages 88-95, ISSN 0956-5663, https://doi.org/10.1016/j.bios.2018.10.010. 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.
Biological nanosensors consist of a bio-receptor and a transducer. The transduction method of choice is currently fluorescence because of the high sensitivity and relative ease of measurement. 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. Even though electrochemical nanosensors can be used to measure intracellular properties, they are typically less selective for biological measurements, as they lack the high specificity of bio-receptors (e.g. antibody, DNA).
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.
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.
Production methods 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.
Top-down methods
Lithography 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. One of the most common method is called electron beam lithography. Although very costly, this technique effectively forms a distribution of circular or ellipsoidal plots on the two dimensional surface. Another method is electrodeposition, which requires conductive elements to produce miniaturized devices.Pison, U., Giersig, M., & Schaefer, Alex. (2014). US 8846580 B2. Berlin, Germany.
Fiber pulling 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.
Chemical etching Two different types of chemical etching have been reported. In the Turner method, a fiber is etched to a point while placed in the meniscus between hydrofluoric acid and an organic overlayer. This technique has been shown to produce fibers with large taper angles (thus increasing the light reaching the tip of the fiber) and tip diameters comparable to the pulling method. The second method is tube etching, which involves etching an optical fiber with a single-component solution of hydrogen fluoride. A silica fiber, surrounded with an organic cladding, is polished and one end is placed in a container of hydrofluoric acid. The acid then begins to etch away the tip of the fiber without destroying the cladding. As the silica fiber is etched away, the polymer cladding acts as a wall, creating microcurrents in the hydrofluoric acid that, coupled with capillary action, cause the fiber to be etched into the shape of a cone with large, smooth tapers. This method shows much less susceptibility to environmental parameters than the Turner method.
Bottom-up methods This type of methods involve assembling the sensors out of smaller components, usually individual atoms or molecules. This is done by arranging atoms in specific patterns, which has been achieved in laboratory tests through use of atomic force microscopy, but is still difficult to achieve en masse and is not economically viable.
Self-assembly