3D IMAGING OF CELLS USING SOUND WITHOUT HARMING CELL

Researchers from Japan and Thailand have employed picosecond ultrasonics to study single cells on a nanoscale. The imaging technique allows a spatial resolution of 150 nanometers, giving the team of scientists the ability to virtually slice cells and tissues without damaging them.

The work done by the research team is a proof­of­concept for using picosecond ultrasonics, which in the past has been used to study the mechanics and thermal properties of metals and semiconductors. Biological tissues are the perfect candidate because they are sensitive to sound velocity, density and impedance.

The collaboration of researchers chose two types of biological tissue – a bovine aortic endothelial cell and an adipose cell (fat cell) from a mouse. The choice to use these cells was not random because endothelial cells play a key role in the physiology of blood cells and fat cells have different cell geometry for contrast.

The work was done by placing a cell into a solution on a titanium­coated sapphire substrate and then scanning a point of high­frequency sound generated by a beam of focused ultrasound laser pulses over the titanium film. Subsequently, by focusing another beam of laser pulses on the same point to register tiny changes in optical reflectance caused by the disturbance of sound, the team was able to gather data to construct an image.

"By scanning both beams together, we're able to build up an acoustic image of the cell that represents one slice of it," explained co­author Professor Oliver B. Wright, Division of Applied Physics, Faculty of Engineering at Hokkaido University. "We can view a selected slice of the cell at a given depth by changing the timing between the two beams of laser pulses."

The results of the team’s work show that 3D imaging of cells and cell organelles is possible without injuring the cell, but is still in the early stages of development. As it stands now, the technique is too time­consuming to be used in everyday practice.

Although in the experiment conducted by the team they were not able to resolve cell contents, they are confident that with improvements, it will be possible. The scientists have several quick fixes on their mind, using an ultraviolet­pulsed laser instead of an infrared laser, which limits spatial resolution and switching to a diamond substrate, which would significantly improve image quality and laser power by allowing better thermal conduction away from the region of interest. These improvements could be the gateway to in vivo imaging, which would give researchers the ability to investigate the mechanical properties of cells and cell organelles. The method will also give us a better understanding of cell behavior, like mitosis, apoptosis, adhesion and mobility.

"The method we use to image the cells now actually involves a combination of optical and elastic parameters of the cell, which can't be easily distinguished," Wright said. "But we've thought of a way to separate them, which will allow us to measure the cell mechanical properties more accurately. So we'll try this method in the near future, and we'd also like to try our method on single­celled organisms or even bacteria."