Taiwan’s Central Research Institute’s Applied Science Research Center’s team of researchers led by Dr. Chen Bizhang has developed a groundbreaking high-resolution optical imaging technology called “Potassium Acrylate Expansion Layer Optical Nanoscopy (KA-ExM).” This innovation allows for brain tissues to be “magnified” up to 64,000 times, making it the first of its kind globally. The achievement has been published in the international journal “Nature Communications.”
The National Science Council held a press conference today (11th) to showcase this academic breakthrough. Present at the event were Lai Ming-chi, Director of the Natural Sciences Division of the National Science Council, Dr. Chen Bizhang from the Applied Science Research Center of the Central Research Institute, and Dr. Lin Zi-yang from the Institute of Cellular and Individual Biology of the Central Research Institute.
Lai Ming-chi mentioned that the successful breakthrough in the technology of “magnifying brain tissues” has enabled optical microscopes to visualize the nano-scale neural world. With the support of relevant National Science Council initiatives, Dr. Chen Bizhang’s team recently published a groundbreaking research in “Nature Communications,” introducing the high-resolution optical imaging technology called “Potassium Acrylate Expansion Layer Optical Nanoscopy (KA-ExM).”
He emphasized that this technology ingeniously combines the “sample space magnification” with the “Bessel layer optical microscope” method, enabling scientists to achieve a three-dimensional imaging of the entire fruit fly brain with a resolution of approximately 10 nanometers, approaching the level of an electron microscope while retaining the optical imaging advantages such as multicolor fluorescence labeling.
Dr. Chen Bizhang explained that traditional optical microscopes are limited by the “diffraction limit,” offering a resolution of only up to 200 nanometers. Spacings less than 200 nanometers will appear blurred and indistinguishable in the microscope. Although electron microscopes can achieve higher resolutions, they operate in a vacuum environment which causes dehydration of the samples, preventing the observation of live samples or the display of colored fluorescence markers.
He further stated that in 2014, three scientists were awarded the Nobel Prize in Chemistry for developing the “super-resolution fluorescence microscopy technology” that can surpass the diffraction limit, leading to various advancements. However, current technologies are still limited to a few cells or thin samples, posing a significant challenge for three-dimensional super-resolution imaging of large tissues.
“This innovation stems from a clever chemical strategy: enlarging the sample before observation.” The research team utilized a highly water-absorbent polymer called “Potassium Acrylate (KA)” to create a hydrogel. The biological samples are then fixed within the gel, similar to the high absorbent material found in diapers, which expands significantly when water is added, enlarging the sample by about 40 times and increasing the overall volume by up to 64,000 times. Consequently, nanostructures that were originally too small to distinguish are “expanded and enlarged,” allowing for clear identification even under an optical microscope.
For example, the original size of the fruit fly brain is only about 0.5 millimeters. After the expansion treatment, it can be magnified to 10-20 millimeters, making it possible to observe the entire neural network. Following the sample enlargement, the team utilizes the “Bessel layer optical microscope” for imaging. This technology uses special “Bessel beams” to produce extremely thin and uniform light sheets, enabling scientists to conduct rapid and highly low photobleaching three-dimensional imaging scans into thick biological tissues.
By combining these two technologies, scientists can not only clearly observe the entire structure of the fruit fly brain but also identify extremely small synapses between nerve cells. Moreover, they can observe synaptic scaffold proteins acting as “cables” for information transmission in the brain and synaptic vesicles acting as “switch sockets” regulating information transfer, crucial for understanding memory, learning, and mechanisms of neurological diseases.
Dr. Chen Bizhang stated that KA-ExM technology possesses high resolution capabilities while covering large-scale imaging and ultra-high spatial resolution. It’s like having a super camera with wide-angle and microscopic lenses, capable of capturing the panoramic view of the entire Taipei 101 building while zooming in to examine the details of an ant colony inside a building.
He mentioned that this technology, with its combination of “large scale” and “nanoscale detail,” can produce a high-resolution “brain structural map,” showcasing the overall structure of neural circuits clearly and tracking subtle changes in local synapses due to learning, damage, or diseases.
He added that in the future, this technology will not only be applicable to fruit fly brains but also holds the potential to expand to other biological samples such as mouse brains or human tissues. It enables in-depth analysis of alterations in neural circuits and disease structures. Its high resolution and three-dimensional imaging capabilities allow scientists to observe biological structures with unprecedented details, driving continuous breakthroughs in basic and applied sciences.