Diamond-based quantum sensing microscope provides an effective approach for quantifying cellular forces

Cells depend on constant interaction and information exchange with their microenvironment to ensure their survival and perform biological functions. Therefore, accurate quantification of small cellular adhesion forces, ranging from piconewtons to several nanonewtons, is crucial for understanding the complexity of force modulation in cells.

Over the past decades, several methods have been successfully developed for measuring cellular adhesion forces. Currently, several leading technologies such as traction force microscopy (TFM), optical/magnetic tweezers, and molecular strain-based fluorescence microscopy (MTFM) are widely used for measuring cellular forces.

However, these techniques have notable limitations in terms of sensitivity and data interpretation, which hinder our ability to fully understand the mechanobiology. Furthermore, the MTFM technique is hampered by the stochastic nature of fluorophore photobleaching.

Therefore, it is essential to develop a new technique that can accurately measure cell adhesion forces in a fluorescent label-free manner. This is crucial for the advancement of the field of mechanobiology.

A project led by Professor Zhiqin Chu from the Department of Electrical and Electronic Engineering at the University of Hong Kong (HKU) and Professor Qiang Wei from Sichuan University applied label-free quantum sensor technology to measure cellular force at the nanoscale. This overcomes the limitations of traditional cellular force devices and provides new insights into studying cellular mechanics, including the influence of cellular adhesion forces on cancer cell spread.

The research team has developed a new Quantum-Enhanced Diamond Molecular Tension Microscopy (QDMTM) that provides an effective approach for studying cell adhesion forces. Compared to cell force measurement methods using fluorescent probes, QDMTM has the potential to overcome challenges such as photobleaching, limited sensitivity, and ambiguity in data interpretation. Furthermore, QDMTM sensors can be cleaned and reused, increasing the absolute accuracy of comparing cell adhesion forces between different samples.

The new method fundamentally changes the way important issues such as cell-cell or cell-material interactions are studied, with significant implications for biophysics and biomedical engineering. The findings were published in Scientific progressin an article titled “Quantum-enhanced diamond molecular strain microscopy for quantifying cellular forces.”

The research team developed QDMTM by combining the elongation of polymer (which acts as a force transducer) induced by cellular forces with the longitudinal relaxation time of NV. The unique quantum properties of NV center electron spins in diamond serve as the fundamental basis for QDMTM’s unprecedented sensitivity and precision.

The uniqueness of this innovation lies in the use of a “force transducer”, a force-responsive polymer, capable of converting mechanical signals into magnetic signals. By measuring the changes in the NV spin relaxation time caused by the magnetic noise, the adhesion forces exerted by cells on the “force transducer” can be determined. Existing measurement techniques are not able to effectively measure the stochastic magnetic signals at the nanoscale.

The innovative QDMTM technique offers an effective approach for studying cell adhesion forces. Through their research, researchers were able to successfully differentiate cells in different adhesion states and found that the magnitude of cellular forces in different cell areas was in line with the previous findings.

This suggests that the QDMTM method is able to accurately measure cell adhesion forces. The next phase of their research focuses on extending the quantum sensor from bulk diamond to nanoscale diamond particles, allowing cell forces to be measured in any direction.