Shape-Shifting Sensors detect Conditions from Inside the Body

Researchers at National Institute of Standards and Technology (NIST) and the National Institutes of Health (NIH) developed a shape-shifting probe enabling new high-resolution remote biological sensing that is not possible with current technology.

A new research report describes alien-like technology that could have major impact on medicine. Scientists from the National Institute of Standards and Technology (NIST) and the National Institutes of Health (NIH) have come up with and demonstrated a new, shape-shifting sensor, about one-hundredth as wide as a human hair. The probe enables sensitive, high-resolution remote biological sensing that is not possible with current technology.

If eventually put into widespread use, the new shape-shifting sensors could have a major impact on research in medicine, chemistry, biology and engineering. 

To date, most efforts to image highly localized biochemical conditions such as abnormal pH and ion concentration—critical markers for many disorders—rely on various nanosensors that are probed using light at optical frequencies. But the sensitivity and resolution of the resulting optical signals decrease rapidly with increasing depth into the body. That has limited most applications to less obscured, more optically accessible regions.

The new shape-shifting probe devices do not have theselimitations. They make it possible to detect and measure localized conditions on the molecular scale deep within tissues, and to observe how they change in real time.

“Our design is based on completely different operating principles,” says NIST’s Gary Zabow, who led the research with NIH colleagues Stephen Dodd and Alan Koretsky. “Instead of optically based sensing, the shape-changing probes are designed to operate in the radio frequency (RF) spectrum, specifically to be detectable with standard nuclear magnetic resonance (NMR) or magnetic resonance imaging (MRI) equipment. In these RF ranges, signals are, for example, not appreciably weakened by intervening biological materials.”

The shape-shifting sensors are called geometrically encoded magnetic sensors (GEMs). They are micro-engineered metal-gel sandwiches about 5 to 10 times smaller than a single red blood cell, one of the smallest human cells. Each consists of two separate magnetic disks that range from 0.5 to 2 micrometers (millionths of a meter) in diameter and are just tens of nanometers (billionths of a meter) thick. (See animation.)

Between the disks is a spacer layer of hydrogel, a polymer network that can absorb water and expand significantly; the amount of expansion depends on the chemical properties of the gel and the environment around it.

Conversely, it can also shrink in response to changing local conditions. Swelling or shrinking of the gel changes the distance (and hence, the magnetic field strength) between the two disks, and that, in turn, changes the frequency at which the protons in water molecules around and inside the gel resonate in response to radio-frequency radiation. Scanning the sample with a range of frequencies identifies the current shape of the nanoprobes, effectively measuring the remote conditions through the changes in resonance frequencies caused by the shape-changing agents.

The scientists tested the sensors in solutions of varying pH, in solutions with ion concentration gradients, and in a liquid growth medium containing living canine kidney cells as their metabolism went from normal to nonfunctional in the absence of oxygen. That phenomenon caused the growth medium to acidify, and the change over time was sensed by the GEMs and recorded through real-time shifting in resonant frequencies.

“Of course, that sort of potential use in living organisms is still a long way off,” Zabow said. “Our data were taken in vitro. And some potential applications of the sensors /4/not be biological at all. But a long-term goal is to improve our techniques to the point at which GEMs can be employed for biomedical uses.”

That would require, among other things, further miniaturization. The 0.5 to 2 µm diameter GEMs in the experiments are already small enough for many in vitro and other possible non-biological applications, as well as possibly for some in vivo cellular related applications. But preliminary estimates by the experimenters indicate that the sensors can be reduced substantially from their current size, and might conceivably be made smaller than 100 nanometers in diameter. That would open up many additional biomedical applications.

The new shape-shifting probe devices have been published online in the journal Nature.