Juntendo University develops affordable 3D imaging microscope for biomedical research

New Delhi: Researchers at Juntendo University have developed a low-cost light sheet fluorescence microscope (LSFM) system, known as descSPIM, designed for three-dimensional (3D) visualization of cleared tissue samples.

The novel system, desktop-equipped selective plane illumination microscopy (SPIM), promises to make advanced 3D imaging more accessible to the biomedical research community.

Three-dimensional imaging of organs and tissues is crucial for providing detailed structural information at the cellular level and identifying pathological conditions. However, existing 3D imaging techniques like LSFM are often too expensive and complex for widespread use. To address these barriers, the team at Juntendo University, led by Associate Professor Kohei Otomo, Takaki Omura, and Professor Etsuo A. Susaki, created the descSPIM system for the visualization of cleared tissue samples.

The research, published on June 12, 2024, in Volume 15 of Nature Communications, highlights the significant advancements in tissue-clearing techniques that have expanded the use of 3D imaging in biomedical applications. “LSFM remain prohibitively expensive for many end users, despite advancements in tissue clearing technologies. When I recognized this bottleneck, I wanted to develop an affordable and sufficiently performing light-sheet microscope to enhance accessibility in biomedical research,” explained Professor Susaki.

The descSPIM system incorporates several unique features to streamline the imaging process. For instance, it replaces the traditional medium chamber with a glass cuvette and employs a two-stage synchronization process during imaging. These innovations reduce the overall time required for imaging and simplify the assembly and operation of the microscope.

The descSPIM system utilizes selective plane illumination microscopy (SPIM), a type of LSFM that employs a thin sheet of light to illuminate cleared tissues. Tissue clearing, a process that renders biological specimens transparent by removing light-scattering components like lipids, is essential for comprehensive 3D imaging. The researchers optimized the design of the microscope to ensure rapid imaging of cleared tissue samples while maintaining high performance and low cost, with prices ranging from $20,000 to $50,000.

The team validated the applications of descSPIM through animal studies, demonstrating its capability for 3D visualization of various cleared tissues and organs. The system successfully imaged volumetric whole-brain samples of transgenic mice, revealing neuronal structures and distributions at cellular resolution. In cancer cell line-derived xenograft (CDX) models, descSPIM enabled the 3D imaging of entire tumor masses, facilitating the visualization of drug distribution within tumor tissues. Additionally, the system generated 3D images of thick tumor sections stained with fluorescent dyes, mimicking standard hematoxylin-eosin (HE) staining, showcasing its potential for future diagnostic applications.

To promote widespread use and collaboration, the researchers open-sourced the design of descSPIM. “Commercial microscopy systems are generally designed as black boxes, where the internal mechanism is unknown to the users. However, the accessible design and open-source nature of descSPIM represent a departure from this norm. Its user-friendly construction and open-sourced nature foster a collaborative environment conducive to the development of pioneering imaging technologies,” said Otomo, the first author of the study.

Researchers worldwide have already embraced the descSPIM system for diverse research endeavors, from imaging various organs such as the brain, hypothalamus, stomach, and intestine in mice and rats, to investigating cancer metastasis in the lungs. “When compared to commercially available light-sheet microscopes, our proposed DIY system is more than 10 times less expensive and strongly supports the dissemination of tissue clearing and 3D imaging technology,” added Otomo.