image: As an analogy to ‘Patch Clamp’ techniques, the authors developed a ‘Quantum Patch Clamp’ technique based on manipulating a single nanodiamond for performing quantum multiphysiology inside a single live cell.
Credit: ©Science China Press
The function of biological activities such as cellular energy conversion and information transfer is thought to be implemented by individual physiochemical reactions accompanied by localized tiny physical signals. A grand dream in understanding life is to directly monitor these reaction outputs at where and when exactly the reaction occurs.
Patch-clamp electrophysiology is still the most direct and effective approach for neuroscience. In contrast to the established electrophysiology, probing the other intracellular-activity-induced multi-physical signals, such as local heat-induced temperature change, local magnetic field, local ROS-generation-induced electromagnetic noise, namely cell multiphysiology, remains an enormous challenge.
Emerging quantum sensing schemes can simultaneously measure multi-physical quantities with sensitivities approaching extreme quantum limit. Due to the atomic length scale, the long coherence time and the multiphysical quantities sensing capability, the NV-based quantum sensors have shown proof-of-concept uses in biological systems. However, delivering high-sensitivity quantum sensing into live cell necessitates a spatially controlled and confined probe-target interaction. More importantly, live cell environment is hydrous, complex and dynamic. The lack of active and precise delivery and manipulation of single quantum objects under biological conditions greatly hinders the achievement of position-controlled quantum sensing inside a single cell. Spatiotemporally resolved live cell quantum multiphysiology remains an unattained goal.
In a new study, “Live cell quantum multiphysiology enabled by a manipulable single nanodiamond”, published in National Science Review, the researchers developed a “quantum patch-clamp” for live cell quantum multiphysiology, which is analogous to the patch-clamp electrophysiology. Their key to realizing “quantum patch-clamp” lies on integrating a single nanodiamond onto a glass nanoelectrode. This enables arbitrary three-dimensional nanoscale positioning of the single nanodiamond NV center (MSN probe) into a live cell and simultaneous measurement of multiphysiology signals at any intracellular site of interest. Thus, they achieved live cell quantum multiphysiology by using a single nanodiamond, comparable to the role of electrical current recording using glass nanopipette in patch-clamp electrophysiology.
They also showed new biological discoveries using MSN enabled live cell quantum multiphysiology. The approach provides an unprecedented spatiotemporal resolution for biological observation. They spatially navigated and scanned the quantum sensor in a live cell and observed a temperature heterogeneity over different intracellular sites. By developing a temporally resolved measurement scheme, they managed to capture the intracellular free radical level mediated local electromagnetic noise changes. Unexpectedly, they observed a number of quasi-periodic oscillation and fluctuation dynamics in different intracellular sites, which may present the rich physiochemical processes in live cells.
Their work may fill the gap between high-physical-sensitivity quantum sensing and high-spatiotemporal-resolution live cell measurement.