An innovative optical microscopy breakthrough, achieved by the research team of Dr. Bi-Chang Chen at Academia Sinica, Taiwan, has dramatically expanded brain tissue up to 64,000 times in volume, allowing unprecedented nanoscale visualization of neural synapses in the whole fly brain. This new technology, Potassium Acrylate Expansion Lightsheet Nanomicroscopy (KA-ExM), integrates chemical sample expansion with Bessel lightsheet microscopy, providing scientists with a revolutionary tool for exploring the neural world.
Breaking Optical Limits
Traditional optical microscopes are limited by diffraction, with a resolution of about 200 nanometers, making smaller structures indistinct. Electron microscopes offer higher resolution but require a vacuum environment, dehydrating and altering samples and removing fluorescence capabilities. The KA-ExM method overcomes these limitations, achieving resolutions of approximately 10 nanometers while maintaining optical microscopy’s advantages, including multicolor fluorescence labeling.
Innovative Chemical Expansion
The research team's innovative approach involves embedding biological samples in a highly absorbent hydrogel made from Potassium Acrylate (KA). Upon hydration, this gel uniformly expands samples by about 40 times linearly, achieving a volumetric expansion of 64,000 times. As a result, nanoscale details previously beyond the resolution of optical microscopy become clearly observable. For example, a fruit fly brain, originally 0.5 mm in size, expands to 1–2 cm, facilitating detailed imaging of neural networks.
Advanced Imaging Capabilities
By integrating expanded samples with Bessel Light-Sheet Microscopy, researchers rapidly obtained deep tissue 3D imaging with extremely low phototoxicity. This combination reveals intricate synaptic details, such as synaptic scaffold proteins and bouton structures critical for understanding memory, learning, and neurological diseases.
Broad Impact and Future Potential
The KA-ExM technique provides comprehensive, large-scale yet highly detailed images, similar to simultaneously photographing the entirety of Taipei 101 along with microscopic details inside the building. This technology holds great promise not only for insect brains but also for mouse and human tissues, potentially transforming neuroscience and biomedical research.
Future Directions
KA-ExM technology is poised to significantly advance our understanding of neural circuits, facilitate the early diagnosis and treatment of neurological disorders, and drive innovations across biomedical sciences.
Media Contact：
Dr. Ting-Yang Kuo
Program Manager/Assistant Research Fellow
Department of Natural Sciences and Sustainable Development
National Science and Technology Council
Tel: +886 (2)2737-7465
e-mail: tykuo@nstc.gov.tw
