Nanosensors: Big Things Come in Small Packages

Ritvik Janamsetty
10 min readMay 1, 2019

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Imagine that you are a student researcher at Harvard University and are trying to solve the world’s most cliché, yet pressing problem of the century — cancer, specifically pancreatic cancer. You have found a new enzyme in the venom of Apis andreniformis that binds only to modified Insulin receptor sites on cancerous pancreatic β-cells, somehow preventing DNA Helicase from being formed. This is huge since this effectively prevents cancer cells from replicating. You do not know the exact biological pathway that this happens, but you have a hypothesis: this new enzyme locally increases the temperature in the cell by inhibiting the thermoregulatory mechanisms of the cell.

But you have a problem: how are you going to measure the temperature inside the pancreatic cells? This is exactly where nanosensors come into the equation. A typical temperature sensor would be practically useless as regular sensors cannot measure temperatures in things as small as cells. Using a nanosensor, you will be able to detect changes in temperature in that small of an area, thus solving your dilemma.

But what exactly are nanosensors? Nanosensors are precisely what they sound like: extremely small sensors. How small? Components of nanosensors are typically measured in units of nanometers (nm), a single of which is 10–9 meters long — in other words, literally microscopic. Figure 1 illustrates the true microscopic scale of a nanosensor.

Figure 1: A nanowire curled into a loop overlaid onto to a single human hair. The diameter of the wire is approximately 50 nm. The width of the hair is roughly a thousand times larger with a diameter of 50 μm. Image from Limin Tong, a visiting professor at Harvard University from Zhejiang University (http://www.tappi.org/content/pdf/events/06NANO-papers/Session%2020%20-%20Dykstra.pdf).

The definition is not limited merely to the physical size of the sensor — a sensor may be classified as a nanosensor if it measures molecules or elements that are in the nanometer range. In fact, as Figure 2 illustrates, many commonly used nanosensors are visible to the naked eye but measure microscopic quantities. While nanosensors that fit this definition are not as smalls as the sensors described in the earlier definition, they are still noticeably smaller than conventional sensors. Most regular sized sensors range from the size of a phone to the size of an entire room; on the other hand, nanosensors are no larger than the size of a postage stamp.

Figure 2: A nanosensor that is being built to detect airborne toxins such as volatile organic compounds, pesticides, and many more in the food supply. The entire assembly is clearly not microscopic, but the molecules that the sensor is measuring are measured in nanometers. Image from FoodNavigator-USA (https://www.foodnavigator-usa.com/Article/2013/06/18/Nanosensor-being-developed-for-food-safety).

Why Does This Even Matter?

Going back to the anecdote presented earlier, imagine trying to measure the temperature of a single cell using a standard mercury thermometer? An electronic thermometer? Or maybe even an infrared thermometer? Good luck with that. The chances are that you will be unable to measure something that small. The only way you would be able to measure it accurately is if you get something smaller than a cell, which can be only done with a nanosensor.

While I could go on and on about particular instances where nanosensors may be particularly useful or even necessary, the general gist is that nanosensors are used in situations where regular sensors are impossible or impractical to use. It is in situations like this that nanosensors become crucial for operation — they make measurements that are otherwise unable to be done reasonably.

Size: This is the most obvious of the benefits. By utilizing nanosensors, one can measure microscopic sizes items such as cells, which would be impossible with other sensors. In other cases, this may make contraptions required to house the sensors much smaller and lighter.

Power Consumption: As the size of a device decreases, so does the power needed to run it. This may be particularly advantageous when building a sensor that remotely powers itself or when a standard sensor would be too expensive to run.

Response Times: When it comes to electronics, response times negatively correlate with wire gauge. The smaller the wire gauge, the faster the response time. In addition, certain sensors simply need long amounts of times to analyze data properly. With nanosensors, it is possible to get real-time data from sensors, significantly cutting the time required.

Precision: Due to the sizes of the sensors and the construction of the sensors themselves, the measurements provided by nanosensors are often very precise. For example, nanosensors can measure pollutants concentrations in units of parts per billion while traditional sensors would only be able to measure it down to parts per million.

Cost: It is, typically, cheaper to build a sensor that is the size of a postage stamp rather than the size of an entire room as it requires fewer resources to produce. While initial costs during research and development may be expensive for nanosensors, these costs often decrease with time to the point that they are radically cheaper than the alternative. In addition, all of the previously mentioned items all work together to minimize cost, whether it by speeding up data analysis or reducing power consumption.

These abilities enabled for great things to be done in many different fields, especially medicine. The advent of nanosensors has allowed for advances in both detection and treatment of disease. For instance, an optical nanosensor can be used to determine the glucose concentration in blood, helping manage diabetes mellitus. Nanobiosensors are being used to determine astronauts’ exposure to radiation damage without the need for blood tests. Finally, nanosensors are being used to detect bacterial infections, viral infections, and cancer. Outside of the medical field, nanosensors are being used to measure gaseous and aqueous pollutant concentrations, to guard against car accidents, and to solve many more issues. It is clear to see the current ways nanotechnology is changing our world — just imagine all the potential.

How Do They Work?

By this point, you probably understood the significance of nanosensors, but you probably do not understand the specificities of the mechanisms nanosensors work. The simplest way to explain how nanosensors work is that they measure some specific quantity and convert it into electrical signals that can be then converted to a quantifiable amount.

The two most common types of nanosensors are chemical and mechanical. Chemical nanosensors measure a physical quantity by measuring the change in electrical conductivity of a sample. An example of this would be the binding of an electron to a Nitrogen Dioxide molecule from a carbon nanotube. This, in effect, decreases the electrical conductivity, resulting in a numerical output. This is typically used in gaseous pollutant measurements. In other situations, a certain protein or other biologically active molecules can bind to a receptor on the surface of a nanosensor and lead to a signal transduction pathway, where it can then be converted into the electrical response. This application is more commonly used in the biological and chemical sciences. This is typically used to measure pH, concentration, volume, pressure, and other properties typically used in chemistry.

Mechanical nanosensors, on the other hand, measure changes in the physical features of an object. For example, a mechanical nanosensor can be used to measure the changes in acceleration or velocity. These changes result in an electrical response that can then be measured. A great example of this in practical use is with airbag deployment in cars. These nanosensors use tiny weighted shafts attached to a capacitor that measures how fast the car is accelerating or decelerating. This data can then be used to determine whether or not to deploy the airbag. This is typically used to measure velocity, gravitational forces, acceleration, displacements, and other properties typically used in physics.

There are still several other types of nanosensors that, while not as popular as the two listed above, are still significant. Optical nanosensors measure the properties of light such as absorption, reflectance, fluorescence, phosphorescence, refraction, interference, and more. They are measured in terms of amplitude or energy. Biosensors are used to detect certain types of biological molecules, such as DNA. Magnetic nanosensors detect changes in magnetism. Temperature nanosensors detect changes in temperatures.

While reading the brief descriptions of all of the different nanosensors, it is crucial to recognize that nanosensors all measure changes in quantity, not an absolute quantity. To put this into context, imagine you just came to the United States, and you have no idea about how the SAT scale works. Imagine you are given a score of 1100 in your first SAT and are given nothing else. You have nothing to compare it to and have no clue what that number means. That is kind of like the data that comes out a nanosensor. To get a readable value, one must compare the data from the nanosensors to a set point. There are two options to analyze the data — compare it to an absolute value or compare it to a set point. Comparing the given to an absolute value would be like comparing your 1100 SAT score to a perfect 1600 and understanding how you performed in absolute terms. On the other hand, comparing it to a pre-established set point is like comparing your SAT score to one of your friends and seeing if you did better or worse than him. Depending on the situation, one might be more useful. Let’s say you want to measure the change in percentage; you would compare it to a pre-determined set point while if you wanted to get an absolute value, such as a temperature reading, you would want to measure it absolutely.

How Are They Made?

The process of manufacturing nanosensors is called nanofabrication. The two most prominent ways of nanofabrication are the bottom-up and top-down approaches.

The top-down method of nanofabrication is analogous to carving a sculpture: a chunk of material is first acquired and then slowly removed to form a particular shape. In other words, this process works like a subtractive process. The most common procedure that this is done is through nanolithography, which itself is split into a multitude of sub-processes: X-ray lithography, ion-beam lithography, photolithography, electron beam lithography, scanning probe lithography, soft lithography, nanoimprint lithography, and more. Despite these differences, the basics of the process are the same: a stencil is etched into a sacrificial layer that is deposited on the main material, and that stencil is etched into the main material. The differences in the different methods of lithography listed above are that each uses a different sacrificial layer and ways to etch the stencil into the base material. Currently, the most common commercial way of top-down nanofabrication is photolithography, more particularly deep ultraviolet lithography. This process is typically used when making electronics, particularly silicon-transistors. Lithography is not the only mechanism as to which top-down nanofabrication is performed; selective dealloying, dissolution, and decomposition of materials are also techniques that, while not as widespread as lithography, are still used.

Figure 3: A representation of top-down lithography. Image from Vinod Kumar Khanna in his book Integrated Nanoelectronics in 2016 (https://link.springer.com/chapter/10.1007/978-81-322-3625-2_23).
Figure 4: A simple illustration of the four most popular methods of top-down nanofabrication. Image from Hai-Dong Yu, Michelle D. Regulacio, Enyi Yea and Ming-Yong Han in their article “Chemical routes to top-down nanofabrication” in the Journal Chemical Society Reviews in 2013 (pubs.rsc.org/en/content/articlelanding/2013/cs/c3cs60113g).

The bottom-up method, on the other hand, works in reverse where individual components are built up from the base. This is analogous to building a house with bricks: one by one and slowly until the needed item is built. In other words, this process works in an additive process. This typically takes place on a substrate that mimics natural processes by catalyzing the formation of molecules from elements. This process — contrasted with the top-down method, is generally used for biological nanosensors along with making extremely microscopic nanosensors, both of which are practically impossible to do with the top-down method.

Figure 5: A visual representation of bottom-up nanofabrication. Image from Vinod Kumar Khanna in his book Integrated Nanoelectronics in 2016 (https://link.springer.com/chapter/10.1007/978-81-322-3625-2_24).

What’s the Catch?

Both of these procedures have their benefits and drawbacks. For example, bottom-up nanofabrication is significantly cheaper than top-down. On the other hand, bottom-up nanofabrication is substantially slower than bottom down. Lasers, while extremely precise, are still prone to mishaps and many times imperfections result from top-down nanofabrication. On the other hand, there isn’t much control on the bottom down process as it is hard to control how individual molecules arrange themselves. Further, only specific substrates can be used, and the substrate selection is often minimal. Also, as stated before, these two procedures also are used for different purposes, with top-down being used in electrical applications while bottom-up is used with chemical and biological purposes.

Figure 6: Simple comparison of top-down and bottom-up nanofabrication. Image from RS Rawat in his article “Dense Plasma Focus” in the Journal of Physics: Conference Series in 2015 (doi.org/10.1088/1742–6596/591/1/012021).

To solve this, I suggest that we look towards embracing new materials. For top-down nanofabrication, I suggest that smaller lasers be used. Rather than using ultraviolet lasers, new lasers can be developed that are in the range of X-rays, so that more energy can be packed into a smaller wavelength, leading to more precise cutting. For bottom-down nanofabrication, new substrates can be potentially be developed by experimenting with already discovered biological enzymes to look for new ways to use those enzymes.

Then there are the issues of nanosensors and nanotechnology as a whole. While nanotechnology is a growing field, it is still a relatively new one — there is much gold that is waiting to be mined in the field of nanotechnology. Due to nanotechnology being a relatively young field, some of the current procedures to make nanosensors are still expensive as the infrastructure simply does not yet exist to mass-produce these devices profitably. In many instances, nanosensors remain a niche product that is only affordable in highly specialized uses. The solution to this gap is rather simple: just partake in more research and prepare the next generation of students for nanotechnology. By doing this, we can help advance the field of nanotechnology and change the world in ways that we do not even know. Nevertheless, the future for nanosensors seems bright.

Thanks to the help of “nanothermometers” — a nanosensor built for measuring the internal temperatures of cells by researchers at Princeton and the University of California, Berkeley — you were able to complete your study. Right as you are about to publish your results, you just think of all of the fame you are going to get. You imagine the amount of money and accolades you are going to get, and it corrupts you. You drop out of Harvard and invest all of your life savings into starting a pharmaceutical company that specializes in the production of the drug. However, once you start testing this drug in clinical trials, you realize that the modified receptors of cancerous pancreatic β-cells are identical to receptors on skin cells… oops. You should have researched more and peer-reviewed your study before you gave up your entire life for it. Now you are homeless and working at a McDonald’s with no money in your bank account. But hey, the nanosensors stood the testament of time, once again proving their efficacy — you can’t blame it for your idiocy.

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