Many factors impact the design of a sensor, and one of them is size. In some cases, a smaller sensor works better, and a teeny-tiny sensor can trigger big advances. Miniaturizing the size of a device toward the nanometer—one billionth of a meter—opens new opportunities in tracking toxins.

“The advantages of nanoscale sensors include an increase in sensing resolution, and a reduction of signal-to-noise ratio” explains Mohammad Ali, postdoctoral research associate at the University of Illinois at Urbana-Champaign in the Beckman Institute for Advanced Science and Technology. “All these features lead the way to lab-on-a-chip detection platform, which provides a ‘fingerprint’ of a chemical constituent in one measurement.”

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Other experts point out more benefits of going nanoscale on sensors. “Nanotechnology sensors are usually more sensitive than their microscale counterpart,” says Daniel Therriault, professor and Canada research chair in fabrication of microsystems and advanced materials in the mechanical engineering department at Polytechnique Montreal in Canada. “The utilization of features at the nanoscale often offer more surface per volume, and several materials offer unique properties at the nanoscale.”

That’s the overview of the benefits of nano-size sensors, but the real advantages come in putting these to work. So far, most of that remains on the research side, but several projects reveal that nanosensors will change tomorrow’s technology.

Shortcomings of size

Despite the many benefits of aiming at nano-size for sensors, it’s not all good news. Taking technology to any limit raises obstacles, and nano-size chemical sensors are no different.

For one thing, the sensor being so small creates what Ali calls a “needle in a haystack” problem. With such a tiny sensor, “the probability of an analyte arriving at the detector is significantly reduced,” he says. “For molecules at low concentration, there is simply a low probability that the molecule ‘runs into’ the nano-size sensor.”

The small size can also create mechanical issues. “The nanosensors might be more fragile and harder to interface with standard data-acquisition equipment,” Therriault says. It’s easy to image such a small size creating a big challenge with connections.

Still, this size realm offers more opportunities than shortcomings.

Finding the needle

“There has been an exceptional amount of research over the past few decades on advanced sensors,” Ali says, “but there has been significantly less effort on methods to rapidly and simply pre-concentrate the molecule of interest and bring it to the sensor.”

The range of applications of nanoscale chemical sensors remains unknown really, but one of the obvious uses involves illegal drugs.

Chem Tox

Getting analytes to a sensor poses a challenge at nanoscale, which can be addressed with a travelling chemical wave that drives directional transport and concentration of molecules (a). Fluorescence micrographs of a hydrogel film show the directed concentration of a hydrophilic dye caused by a travelling wave. (b). Fluorescence microscope images of a hydrogel film taken during the directed concentration of hydrophilic dye via travelling wave. (Image courtesy of Mohammad Ali, University of Illinois at Urbana-Champaign.)

So, Ali and his colleagues study ways to transport target molecules to the sensor. “Our recently published paper in Angewandte Chemie describes a method to transport and concentrate the molecule of interest by using traveling ionic waves,”1 Ali says. “The traveling ionic wave is triggered by the introduction of spatially localized ions, which through a dissipative ion-exchange process converts quaternary ammonium groups in the hydrogel from being hydrophilic to being hydrophobic.” This technique increased the concentration of a hydrophilic dye—used for demonstration purposes—by 70-fold.

“From this, we could build a device capable of manipulating complex mixtures of chemicals for lab-on-a-chip applications,” Ali explains. “This is groundbreaking, the first time it has ever been done.”

3D detection

Therriault and his colleagues used 3D printing of conductive structures to make liquid sensors.2 “We 3D printed different porous structures made of a thermoplastic combined with carbon nanotubes—that is, nanocomposite material,” he explains. “The material’s electrical resistivity significantly changes when exposed to harsh liquid chemicals, such as acetone.”

To do this, Therriault combines the thermoplastic with a solvent to make a liquid. Then, adding carbon nanotubes makes thick black ink, which is almost as conductive as some metals. This composite ink—nanotubes and thermoplastic—can be used in 3D printing.

This process makes a sensor that uses nanoscale elements that can identify a liquid. “The structure’s microscopic porosity facilitated the wettability of the network while the high electrical conductivity of the composite facilitated the reading of the sensing response,” Therriault notes.

These sensors could be used in many ways, including putting them in textiles.

Detecting drugs

The range of applications of nanoscale chemical sensors remains unknown really, but one of the obvious uses involves illegal drugs. In China, a group of scientists used nanosheets to build a cocaine sensor.3

These scientists made nanosheets from zirconium-based metal plus organic components, and embedded that with silver nanoclusters. This material, the scientists wrote, “exhibited strong bioaffinity toward biomolecule-bearing phosphate groups.” So, the surface can hold structures, called aptamers, that bind to cocaine. This research showed that the sensor detects cocaine down to fractions of a picogram—just one trillionth of a gram—in a milliliter of sample.

Consequently, these scientists concluded: “As expected, with the advantages of high selectivity, repeatability, stability, and simple operation, this new strategy is believed to exhibit great potential for simple and convenient detection of cocaine.”

Moving medicine ahead

The dangerous substances identified with nanoscale sensors can also impact medicine. At the Massachusetts Institute of Technology, Sangeeta Bhatia—director of the laboratory for multiscale regenerative technologies—and her colleagues developed a nanosensor from thermosensitive liposomes.4 Using magnetic nanoparticles, these liposomes can be activated at the disease location with alternating magnetic fields.

Bhatia and her team used this sensor to explore differences in the development of tumors. “We applied this spatiotemporally controlled system to determine tumor protease activity in vivo and identified differences in substrate cleavage profiles between two mouse models of human colorectal cancer,” they wrote.

As these examples show, very small devices—or components of them—can turn into very big opportunities. To a certain extent, pushing the devices down to the realm of nanometers appears to make the range of opportunities even broader. As indicated, though, going nano is not completely free of challenges. Moreover, moving this technology from the research realm to the market is likely to take some doing, but that is clearly the path forward for some applications in sensing toxic chemicals, as well as identifying substances that cause disease.

References

1. Tsai T -H, et al. “Dynamic gradient directed molecular transport and concentration in hydrogel films,” Angewandte Chemie 56:5001–5006, 2017. [PMID: 28370916]

2. Chizari K, et al. “3D printing of highly conductive nanocomposites for the functional optimization of liquid sensors,” Small 12:6067–6082, 2016. [PMID: 27624576]

3. Su F, et al. “Two-dimensional zirconium-based metal–organic framework nanosheet composites embedded with Au nanoclusters: A highly sensitive electrochemical aptasensor toward detecting cocaine,” ACS Sensors, 2017 [epub before print]

4. Schuerle S, et al. “Magnetically actuated protease sensors for in vivo tumor profiling,” Nano. Lett. 16:6303–6310, 2016. [PMID: 27622711]

Image: This scanning electron micrograph shows a nanocomposite 3D-printed liquid sensor in a multilayer scaffold configuration. Each filament is close to 100 microns in diameter. (Image courtesy of Daniel Therriault. Photograph by Kambiz Chizari.)