NANOSENSORS *
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4.6 CURRENT RESEARCH AND FUTURE PERSPECTIVES
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4.5.4 INDUSTRIAL
Nanosensors also have useful applications in the industrial field. One of the most prominent applica- tions is the ability to detect various industrial gas leaks. Techniques to detect gas leaks include the use of detecting chemical agents such as differential absorption, light detection, and ranging, along with terahertz frequency-based sensing systems. These two systems are capable of detecting gas at ppm to ppb ranges and are portable and easy to use. The sensor is based on a ridged wave guide with various dielectric materials that are structured periodically in an array. The sensor functions by detecting the concentration of industrial gas changes based on the changes in the effective refractive index of the core in the sensor while the industrial gas fills up the receptor space. This type of sensor is small and portable allowing for easy use and a wide range of applications in detecting industrial gases. The three gases that were tested in this cause were: hydrogen sulfide, carbon dioxide, and sulfur dioxide (Sengupta, 2009).
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A promising application for nanosensors is their use for breath analysis. Analysis of bodily fluids (blood, sputum, and urine) is important for disease diagnosis and monitoring. However, noninvasive ways, such as breath analysis, are currently underdeveloped. Among 400 compounds that are in human breath, only 30 have been identified and most are potential indicators for more than one disease. For example, CO levels are markers for cardiovascular diseases, diabetes, nephritis, etc. Gouma et al. have developed a metal oxide-based nanosensor to detect ammonia gas in a breath-simulating environment FIGURE 4.15
A hybrid nanosensor: this sensor was used to detect for tNt. See the text for more information.
From Aguilar, A. (2010). A hybrid nanosensor for TNT vapour detection. Nano Letters. American Chemical Society, 380–384.
FIGURE 4.16
Sensor response to different analytes. (A) ΔVg is the shift of the Id versus Vg curve of the pEdOt nanojunction.
(B) ΔIEc is the electrochemical reduction current measured by WE3 at − 1.2 v. the response to tNt is stronger in both graphs.
From Aguilar, A. (2010). A hybrid nanosensor for TNT vapour detection. Nano Letters. American Chemical Society, 380–384.
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at ppb concentrations, with a lower bound of 50 ppb. Ammonia is important because it can differentiate between viral and bacterial infections in lung diseases to justify the use of antibiotic. The sensor was shown to be reversible; response and recovery times were extremely fast (milliseconds to seconds), and the expected lifetime is over 1 year at operation temperature (Gouma, 2010). Furthermore, the nanosen- sor was shown to work up to 25% humidity with no effect on performance.
Many other nanosensors have been developed to detect certain substances in the breath. Yet another example is a nanosensor prototype by Wang et al. (2011) to detect acetone in a single breath sample.
Acetone is a biomarker for type 1 diabetes. This specific sensor’s detection mechanism is done by ε-WO3, a type of ferroelectric material that has spontaneous electric dipole moment. This polarity comes from the displacement of the tungsten atoms from the center of each WO3. Acetone has a much larger dipole movement than any other gas, and as a consequence, interaction between the acetone and WO3 produces a strong current that is detectable.
Breath analysis can also be used to detect certain types of cancers. Tumor growth involves gene/
protein changes which may lead to oxidation of the cell membrane. This can be detected by the emis- sion of VOCs in the patient’s breath. Peng (2010) investigated the ability to distinguish between breath VOCs that characterize healthy states and those that indicate different types of cancer using a nanosen- sor array. Breath samples were collected from 177 individuals aged 20–75 years of age. The volunteers included several different types of cancer patients (lung, colon, breast, and prostate), as well as healthy controls. A nanosensor array made of 14 GNP sensors was used. Each sensor goes through a rapid change in electrical resistance when exposed to the sample. These resistance changes were measured and the signals were analyzed using principal component and cluster analysis. The results showed that the nanosensor array was capable of differentiating between the breath of cancer patients and the healthy controls as shown in Fig. 4.17A–D. It was also capable of distinguishing between the different cancer types (Fig. 4.17E). Such nanosensors could lead to the development of a noninvasive, easy to use, inexpensive alternative method for cancer diagnostics.
Cancer can also be detected by analyzing the activity of telomerase. Human telomerase is a ribo- nucleoprotein reverse transcriptase that catalyzes the addition of telomeric units to the telomere ends of each chromosome (Perez, 2008). It is a key oncogenic gene. Currently there are a number of novel telomerase inhibitors that are being developed. Current technologies used to measure the presence and enzyme activity are time consuming and prone to false positives or false negatives. Perez (2008) has developed a set of function magnetic nanosensors capable of measuring the concentration and enzy- matic activity of telomerase. The method of detection is based on a magnetic relaxation switch assay that is able to detect the presence of telomerase protein activity and presence in various cancer and normal cell lines. Two sets of nanosensors are involved. One set of magnetic nanoparticles is conju- gated to telomeric repeat oligonucleotides, resulting in nanosensors able to measure telomerase activ- ity. Another set is conjugated to anti-hTERT antibody, resulting in a nanosensor that detects different amounts of telomerase protein. Measurements of telomerase activity and presence are performed by measuring the difference of T2 in a water relaxation environment (Grimm, 2003) (Fig. 4.18).
Nanosensors may also be used to detect health conditions other than cancer. One example is diabe- tes. Currently there is no cure for diabetes. At the individual level, diabetes is managed by the monitor- ing and control of glucose levels in the blood in order to minimize the effects of the disease. Today, diabetes patients typically do this by obtaining a small sample of blood, usually a finger prick, which is then placed on a sensor strip and read by an electronic reader which reports the blood glucose concentration. This method has limitations such as painful sampling and noncontinuous monitoring.
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Nanomaterials have already improved the size, lifetime, accuracy, and usability of sensors that are cur- rently in use, but in recent years the focus has been on nanosensors that can directly measure glucose levels, and a system that is capable of continuous monitoring.
A solution that is currently being developed involves fluorescent-based nanosensors. These types of nanosensors offer the benefit of providing continuous monitoring and can be implanted into the skin.
This approach is referred to as a “smart tattoo” (Fig. 4.19A), where the nanosensors would change fluorescence properties in response to the blood glucose level.
This method could eliminate the need for patients to take blood samples and minimize the risk of infection. Several nanosensors have been developed using fluorescence signals that could possibly be used in this process. One type of nanosensor that could be used as a step toward developing a “smart tattoo,” are fluorescent nanosensors that are based on highly plasticized hydrophobic polymers (Fig.
4.19B). The core of the nanosensor consists of hydrophobic boronic acid that is capable of extracting glucose. In the absence of glucose, the boronic acid binds the nonfluorescent alizarin, while in the pres- ence of glucose, the boronic acid binds glucose, releasing alizarin and decreasing overall fluorescence.
The sensors are reversible because the components are hydrophobic and remain in the core of the sen- sor. This allows for continuous monitoring. The development of these nanosensors represents a major step in the development of a smart tattoo for continuous, real-time glucose monitoring in diabetes patients.
FIGURE 4.17
Results from the cancer detection study. pcA plots of the gNp sensor array’s resistance responses of cancer with healthy controls: (A) lung cancer, lc, (B) colon cancer, cc, (c) breast cancer, Bc, (d) prostate cancer, pc, and (E) all cancer patients and healthy controls together.
From Peng, G. (2010). Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a sing array of nanosensors. British Journal of Cancer, 542–551.
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Nanosensors can be of much importance in cellular biology. For example, Kuang and Walt (2007) used self-assembled fluorescent nanosensors to detect oxygen consumption in the proximity of Saccharomyces cerevisiae. Oxygen concentration can provide information about certain cell charac- teristics, such as their “viability upon exposure to cytotoxic drugs and environmental stress, protein synthesis capability, mitochondria function,” etc. The synthesis of the nanosensors began as amine functionalized 100 nm polystyrene nanobeads were first covalently conjugated with polyethylenimine (PEI) and soaked with a ruthenium (II) complex that was oxygen-sensitive. This produced a florescent oxygen nanosensor with ruthenium (II) complex entrapped throughout the inert but highly oxygen-per- meable polystyrene matrix. The resulting oxygen nanosensors were then assembled on cell surfaces via electrostatic interactions between the positively charged PEI and the negatively charged S. cerevisiae cell surface at a physiological pH of 7.4. Once the oxygen nanosensors were ready, the authors incubated them with cultured yeast cells at different cell/nanosensor ratios. The number of nanosensors on each cell FIGURE 4.18
process of using MRi and nanosensors for enzyme and human telomerase detection. the cell extract containing telomerase protein is incubated with a sensor in solution. t2 relaxation time changes (induced by clustering of nanoparticles; blue (dark grey in print version)) are measured, as they are proportional to the levels of telomerase activity and amount of telomerase protein.
From Perez, J. M. (2008). Integrated nanosensors to determine levels and functional activity of human telomerase. Neoplasia.
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was controlled by varying the concentration of the stock nanosensors. The results showed that cells cov- ered with higher numbers of nanosensors showed strong fluorescence (Fig. 4.20).
Yeast cells coated with oxygen nanosensors were deposited into a single cell microwell array such that many cells were individually and simultaneously monitored. The authors’ results success- fully tracked the temporal profile of oxygen concentration change measured by the nanosensors.
The authors concluded that this demonstrated that the dynamics of oxygen consumption can be noninvasively and sensitively measured in the proximity of individual cells with self-assembled nanosensors. The nanosensors measured the oxygen concentration directly at the cell surface, sug- gesting that other analytes with slower diffusion rates and more rapid kinetics could be measured in a similar manner.
FIGURE 4.19
Nanosensor solution for diabetes. (A) Smart tattoo. (B) A type of nanosensor based on highly plasticized hydrophobic polymers.
From Kevin, C. (2010). Nanosensors and nanomaterials for monitoring glucose in diabetes. Trends in Molecular Medicine. 16.
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Since nanosensors are still in development, much research is also done to investigate methods of assembling these sensors. Many studies have been published examining novel ways of assembling cer- tain types of nanosensors. One example is the work by Blum, Soto, Sapsford, and Wilson (2010), who have examined the bottom–up self-assembly for electronic nanosensors, in which the recognition of a binding event transfers directly into a readable electronic signal. The designed nanosensors consisted of a molecular electronics-based network built on a cowpea mosaic virus (CPMV) capsid scaffold.
The CPMV was used for binding cysteine (cys) residues and anchoring GNPs to specific locations on the scaffold. The gaps between the GNPs were adjusted such that a 3D conducting network could be constructed on the nanoscale. The conductance of such molecular networks can be measured upon exposing them to the analyte.
As evident from the wide variety of studies done, there is no doubt that nanosensors have great potential, as they continue to provide more effective and simpler alternatives to many existing sensors.