Quantum technology for imaging life at the nanoscale

University of Melbourne researchers have revealed a ‘quantum kangaroo’ that demonstrates a way to detect and image electronic spins non-invasively with ambient sensitivities and resolution orders of magnitude never before achieved. Published in the journal Nature Communications, their breakthrough will provide physicians and researchers with a new tool for probing the role transition metal ions play in biology and disease.

Electron spin resonance (ESR) techniques have long been a mainstay in understanding biochemical processes in biological systems. Yet ESR has not seen the rapid growth compared to its sister technology, nuclear magnetic resonance (NMR), which is used in magnetic resonance imaging (MRI) to look inside the body.

Both ESR and NMR apply a magnetic field to image molecules, but unlike NMR, ESR can reveal biochemistry related to metal ions and free radicals. The challenge is that in biological systems the detectable concentration of electron spins is many orders of magnitude lower than nuclear spins. Hence, the roadblock for the development of ESR-based imaging techniques has been the sensitivity required — typically billions of electronic spins have been needed to generate a sufficient signal for successful imaging.

Now, researchers led by Professor Lloyd Hollenberg have used a specially engineered array of quantum probes in diamond to demonstrate non-invasive ESR imaging with subcellular resolution. Their system is able to image and interrogate very small regions containing only a few thousand electron spins.

“The sensing and imaging technology we are developing enables us to view life in completely new ways, with greater sensitivity and resolution derived from the fundamental interactions of sample and probe at the quantum mechanical level,” said Professor Hollenberg, who is deputy director of the ARC Centre for Quantum Computation & Communication Technology (CQC²T).

“This dramatic improvement in ESR imaging technology is an exciting development and a clear demonstration of how quantum technology can be used to enhance signal sensitivity and provide solutions to longstanding problems, for example, probing human biochemistry at even finer scales.”

Scaling ESR technology down to sub-micron resolution has been challenging because such a reduction in spatial resolution requires substantially better sensitivity. Yet this is precisely what quantum probes offer — high sensitivity with high spatial resolution.

By generating an array of quantum probes in diamond, using the material’s unique nitrogen-vacancy colour centre, the interdisciplinary research team was able to image and detect electronic spin species at the diffraction limit of light: 300 nm. The sensing technology is also able to provide spectroscopic information on the particular source of electronic spins being imaged.

Schematic representation of a quantum probe array in diamond (red arrows representative of the NV quantum probes) performing electron spin resonance (ESR) imaging of hexaqua copper (II) ions above the diamond’s surface. A green laser controls the quantum state of the probe, an external magnetic field is tuned to the resonant frequency target copper (II) spins. The quantum probe responds to the presence of the copper (II) spins and provides a direct readout via the red light emitted. Image credit: David Simpson.

Lead author Dr David Simpson, from the university’s Centre for Neural Engineering, said the technology can provide new insight into the role transition metal ions play in biology. He noted, “Transition metal ions are implicated in several neurodegenerative diseases; however, little is known about their concentration and oxidation state within living cells.

“We aim to adapt this new form of sensing to begin probing such effects in a range of biological systems.”

One of the advantages of quantum-based sensing is that it does not interfere with the sample being imaged. Other approaches rely on fluorescent molecules binding to particular targets of interest. While these approaches are species-specific, they modify the functionality and availability of the target species being imaged.

“Our technique relies on passive, non-invasive detection of electronic spins by observing their interaction with the quantum probe array,” said PhD student Robert Ryan, a co-author on the paper.

“By carefully tuning an external magnet into resonance with the quantum probes, we are able to listen to the magnetic noise created by the sample’s electronic spins. Different electronic spin species have different resonance conditions; therefore, we are able to detect and image various electronic spin targets.”

Top image caption: Electron spin image of copper (II) ions in a patterned region of the diamond defined by the kangaroo. The scale bar in the image is 10 µm. Image credit: David Simpson.