Most efforts to image highly localised 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, described in the journal Nature, are not subject to those limitations.
They make it possible to detect and measure localised 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," said US National Institute of Standards and Technology (NIST)'s Gary Zabow, who led the research with National Institutes of Health (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," said Zabow.
As a result, they can get strong, distinctive signals from very small dimensions at substantial depths or in other locations impossible to probe with optically based sensors.
The novel devices, called geometrically encoded magnetic sensors (GEMs), are microengineered 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 micrometres (millionths of a metre) in diameter and are just tens of nanometres (billionths of a metre) thick.
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.
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 quickly identifies the current shape of the nanoprobes, effectively measuring the remote conditions through the changes in resonance frequencies caused by the shape-changing agents.


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