At the 2022 edition of the International Exhibition of Inventions of Geneva last April, researchers from CUHK walked away with 17 awards out of the 800 entries from 25 countries presented by a panel of international jurors. Among them, the Faculty of Engineering took home one gold and two silver medals.

Among the new inventions recognised as the most innovative solutions to societal issues impacting people’s quality of life, the ultrafast oscillating blade microtome by Professor Shih-Chi Chen at the Department of Mechanical and Automation Engineering clinched a gold medal.

Professor Chen had recently developed the microtome with the support of a team to enable the visualisation of biological organs at subcellular resolution when integrated with high-performance fluorescence microscopes, which include confocal laser scanning microscopes and two-photon excitation microscopes with the optical cross-sectional capabilities to visualise biological specimens at video frame rates. A microtome is a common cutting instrument in every pathology laboratory for creating thin tissue sections for histopathology. However, conventional microtomes can only be used for processing fixed or hardened tissues, not sectioning soft or fresh tissues.

The invention of the ultrafast oscillating blade microtome is crucial to deepening our understanding of our biological organ properties and functions. Although the aforementioned fluorescence microscopes already provide clear cross-sectional images, their penetration depths are typically limited to tens to hundreds of microns, owing to severe light scattering and absorption effects in biological tissues. Considering that biological organs are often measured on a centimetre-scale, imaging below the surface of a one-millimetre depth or beyond is still constrained by the working distance of the objective lens (less than a few hundred microns for high numerical aperture objectives), even after the tissue clearing technique is applied to eliminate scattering problems. In addressing these challenges, the microtome can precisely remove soft tissue layers in images while minimising tissue distortion.

As similar challenges also exist in “expansion microscopy”, a popular technique in recent years to achieve super-resolution imaging via a regular fluorescent microscope by expanding a biological specimen at over 1,000 times in volume (achieved by synthesising a swellable polymer network within the biological specimen), the need arose for the development of a new class of microtome to slice soft tissues, organs, or other synthetic materials into thin sections for microscopic study and imaging. Typically, these sequentially imaged sections are assembled to reconstruct a 3D image.

The ultrafast oscillating blade microtome operates based on an oscillating blade at an ultrahigh speed of 350Hz to enable the tissue self-stiffening effect. An increase in cutting speed automatically hardens tissues without the need for chemical or similar treatments (e.g., freezing). To constrain the parasitic motions of the blade in the cutting plane to within one micron, which is extremely difficult for an instrument of low natural frequency (<100Hz), Professor Chen and his team's solution is based on a unique multi-symmetric flexure mechanism in combination with active control technology, where the mechanism provides nanometre-level repeatability and minimal out-of-plane vibration, so that the vibration control circuit actively generates the necessary forces and torques to cancel unwanted dynamics. To date, the microtome is already setting new records on cutting precision and speed to enable the precise sectioning of fresh tissues (e.g., brain), the optical clearance or expansion of tissues, and 3D imaging of entire organs at subcellular resolution or even super-resolution levels when integrated with advanced microscopy platforms.

Currently, the ultrafast oscillating blade microtome is being featured in several collaborative projects with MIT and Boston University to visualise detailed neuronal networks in human brains for the first time in history. To complement these knowledge-transfer opportunities, a CUHK spin-off company, Precision Cut Limited, has been formed to commercialise the promising technology in the wider market.

All these efforts have placed CUHK in the company of world-renowned universities and research institutions at InnoHK, an initiative spearheaded by the Innovation and Technology Commission to build up a pool of talent and foster more collaboration between top researchers in the industry to achieve synergy and translate research outcomes into applications. So far, the Faculty of Engineering has launched three research centres under AIR@InnoHK, one of InnoHK’s two research clusters which focuses on AI and robotics technologies. In the future, it hopes to be involved in more similar clusters, as it sets its sights on advancing the forefront of health and medicine to benefit the scientific community in Hong Kong and beyond.