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Through Cross Field Collaboration to Develop New Cutting-edge Instrument and Find Answers for Human Brain Diseases

News on February 14, 2021

In her inaugural address last year, President Tsai Ing-wen declared that "to create biotech and medical technology industries integrated with the rest of the world" is one of the six core strategic industries. Meanwhile, the Ministry of Science and Technology (MOST) is promoting an inter-ministerial project of "Taiwan Precision Health Strategic Development Plan" to layout Taiwan's precise health blueprint with BioICT and expects to drive the next wave of biomedical technology innovation and development.

In biomedical industry, both reagent manufacturing and new drugs and vaccines development all base on clinical observation and data collection. Taiwan Instrument Research Institute (TIRI) of National Applied Research Laboratories (NARLabs) under MOST,  having more than 45 years of optical and vacuum technology research and development energy, assists the Academia Sinica's research team of "constructing high-resolution 3D brain images" custom-developing the large-aperture high-resolution optical microscope objective for "Light-Sheet Microscope"[1], which is expected to facilitate major advances in the study of tissue physiology and pathology research.

TIRI has tailor-made "Large Aperture Microscope Objective for Mouse Brain Research" for the team led by Dr. Bi-Chang Chen, Associate Research Fellow at Research Center for Applied Sciences of Academia Sinica. The large-aperture microscope objective with large-scale imaging field of view (diameter 22 mm) and high spatial resolution (1 μm), can obtain one layer of high-resolution images of the intact mouse brain in one shot. This breakthrough technology improves the problem of narrow imaging range and image stitching, greatly increasing the efficiency of imaging and research. The microscope can be applied to high-resolution wide-field imaging and 3D image construction for brain research. It will help the research team further explore the mouse brain in the future, reveal the mechanism related to protein distribution, and discover the answers to some human brain diseases.

TIRI has been cooperating with associate researcher Bi-Chang Chen since 2014 to customize and develop exclusive microscope objective according to his requirements for "lattice light-sheet microscopy" system. Associate researcher Bi-Chang Chen and research team lead by Academician Ann-Shyn Chiang, Professor of the College of Life Sciences and Director of the Brain Science Center of National Tsing Hua University, used TIRI's customized microscope objective to develop the world's only "transparent light sheet localization microscope" made entirely in Taiwan.

The microscopy makes it possible for human being to "observe the memory" for the first time by observing the quantity and spatial distribution in specific cells of proteins produced during the formation of memory. The results of the observation and application of the "transparent light sheet localization microscope" in the fruit fly brain were published in "Nature Communications" in 2019. The research team plans to further develop the study and application in the mouse brain, which led to the collaboration with TIRI once more.

The cross-field collaboration model builds on academic partners' advanced research requirements, and then the specifications are set by TIRI's expert team. After the requirements and specifications are confirmed by both parties, TIRI performs a full range of customized services from design, processing, assembly to testing; then finally academic partner and TIRI jointly verify and confirm the service product performance.

TIRI is taking on constructing a cross-field integrated instrument technology research and development service platform. Being the only domestic organization that can provide customized service for special key modules and instruments development for academic community to meet the special requirement for advanced research and experiments in various fields, TIRI is constantly targeting to explore new discoveries in science. As an important R&D institute for key instruments in Taiwan, TIRI focuses on the fields of "advanced optics", "advanced vacuum" and "smart biomedicine". TIRI is also devoted to the discovery and development of innovative "Taiwan No. 1" & "international leading" next-generation semiconductor process equipment, cutting-edge defense, space payload systems and anti-epidemic related equipment to help improve people's well-being.

 

Large-aperture microscope objective, used in mouse brain research, 43.8 cm in length and 17 cm in diameter

 

[1] Light sheet microscope: It generates a thin sheet of light with a width of only 500nm from the direction perpendicular to the microscope objective lens, and illuminates the focal plane of the sample to be observed to image biological samples with very fine resolution. If many light sheets are emitted to different focal planes of the sample to be observed at the same time, a 3D and real-time microscopic appearance of the sample can be obtained through quickly imaging each focal plane. It can achieve long-term tracking and observation of living samples such as cells.