Fibre laser microscope for analysing molecules in cells

Researchers from The University of Hong Kong (HKU), in collaboration with Bielefeld University in Germany, have developed a compact fibre laser microscope that will assist in analysing molecules in cells and clinical applications.

The microscope is said to generate far less noise than customary designs, and its compactness and stability make it suitable for use in operating rooms in hospitals. It has been described in the journal Light: Science and Applications.

When investigating how tumours grow, or how pharmaceuticals affect different types of cells, researchers have to understand how molecules within a cell react — and interact. This is possible with modern fluorescence microscopy; however, molecules in cell specimens have to be labelled with fluorescent substances to make them visible, and this can distort the very behaviour of the molecules. Staining with fluorescent markers is also generally unsuitable for in vivo tissues.

The newly invented laser microscope does not require fluorescent markers to obtain a clear image of cell molecules. Instead, cell molecules with different level of characteristics are uniquely presented via a Raman imaging system.

“We use fibre laser as the light source of the optical microscope to replace the traditional solid-state laser, which is a brand new concept,” said HKU’s Professor Kenneth Wong, who led the research.

“Traditionally, the laser needs to be amplified in a free space of several metres, so the instrument is very big. With fibre lasers, light is amplified and transmitted through glass fibres, and the instrument design becomes light and compact. The volume is only one-eighth to one-tenth of the traditional solid-state laser instrument.

“Fibre lasers were previously not favourable for microscopes because they were less powerful and very noisy compared to solid-state lasers. To obtain molecule-specific imaging with their microscope, the team used two synchronised optical resonators (laser cavities), both with short picosecond pulses — one picosecond being one thousand billionth of a second.”

“One challenge here was to control the lasers so that both beams with different wavelengths are synchronised, and hit the specimen at exactly the same time and position,” added Professor Thomas Huser, a biophysicist at Bielefeld University.

Prof Huser believes that the new microscope is likely to be used in clinical applications in the coming years. Preliminary studies in cooperation with the Evangelisches Klinikum Bielefeld hospital are already underway to use the microscope to analyse liver tissue samples.

“Our project partners are amazed by what this microscope can do,” Prof Huser said. “Label-free microscopy can be used, for instance, to investigate how various new types of cells develop from stem cells. It also allows for a tumour to be demarcated from normal tissue without staining. Furthermore, we can ascertain how pharmaceutical compounds react with molecules in the muscle tissue cells of the heart and liver, as well as other cells.”

Prof Wong believes the new technology can be applied in many biomedical applications, such as endoscopies of the intestines and digestive system to detect early tumours and lesions.

“Using fibre laser, the image clarity can be 100 times higher than that of traditional endoscopes. It can penetrate the surface of organs and reflect the condition of deeper tissues. The light source uses harmless infrared visible light and will not affect the human body,” he said.

“In the long run, since it is portable, unmarked and harmless, it can be clinically used in surgical operations, such as immediate pathological detection, to mark tumour borders during an operation, or to accurately mark different parts for precise cuts during brain surgeries.”

Lead author Dr Cihang (Sherry) Kong, a former PhD student of Prof Wong and currently a postdoctoral researcher of Prof Huser, concluded, “The prototype of the microscope will now serve as the basis from which to build portable devices. Because the molecules do not first have to be labelled, the specimen does not take a long time to prepare compared with using other microscopes and the labelling-induced toxicity can be avoided.”

Image credit: ©stock.adobe.com/au/Jezper

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