Olympus Corporation (President: Tsuyoshi Kikukawa) has developed two in vivo fluorescence molecular imaging systems for use with small animals. One is the Micro laser scanning microscope system capable of micro-level observations which was developed through a research program funded by a NEDO grant *2. The objective lens of the microscope is the world’s smallest diameter at just 1.3mm, allowing the microscope to be used for in vivo fluorescence observation of organs, etc., in small animals. Another is the In vivo fluorescence observation system, which allows external observation of fluorescence signal in small animals. It features a new optical system that supports high-sensitivity observations across a wide range of magnifications. |
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This technology allows real-time monitoring of phenomena that only occurs in vivo, such as cancer metastasis and blood flows. It also has the potential to contribute in many other fields, such as research into drug efficacy and the treatment of diseases. Olympus will continue to develop this technology with a view to its eventual commercialization and use in humans in the future. |
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Fluorescence molecular imaging: This technology uses fluorescence to analyze the dynamic states of cells and molecules in order to analyze the molecular functions that control biological phenomena in living body. The aim is to develop pharmaceuticals and therapies by using dynamic analysis of fluorescence-labeled compounds or localized analysis of cancer cells or proteins as systems, thereby providing a visual representation of the dynamic states of molecules. |
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NEDO grant research program: The New Energy and Industrial Technology Development Organization (NEDO) provided a grant for a research program (2001-2003) leading to the development of a practical endomicroscope. The aim was to establish multi-wavelength endomicroscopy technology as the basis for a practical laser scanning microscope system that could be inserted into the channel of an endoscope. |
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In Vivo Fluorescence Observation System |
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The In vivo fluorescence observation system is an imaging system that allows highly sensitive detection of fluorescent signals out of the bodies of small laboratory animals. The optical system has a wide range of magnification, from macro-level observation of an small animal, to observation of microscopic locations at the cellular level. With this system, it is possible to monitor in vivo processes in small laboratory animals, including the behavior of molecular chains, the metastasis of cancer, and the effects of drugs administered to the subject. |
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Overview of Main Features |
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New optical system — supports highly sensitive in vivo observations of small laboratory animals from outside of the body, detecting weak fluorescence signals |
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Rapid adjustment across a wide range of magnifications from micro to macro levels |
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Automatic adjustment of CCD camera and optical system to ensure optimal observation at each magnification |
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Reasons for Development |
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Molecular chains (signal pathways) are responsible for all biological phenomena. There has been a growing need in recent years for molecular imaging equipment capable of observing molecular behavior in vivo. Molecular targeting drug *3 offer enormous benefits, including the ability to treat diseases by interrupting the molecular chains that cause them. Moreover, progress in the life sciences has narrowed the gap between basic research and clinical practice. This trend has heightened the importance of “translational research,” the purpose of which is to link seeds created by basic research with the needs of clinical medicine. |
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This newly developed microscope technology allows wide-ranging in vivo observation of small animals from the micro level to the macro level. It was developed for use in various fields, including medicine, biology and pharmacology, as well as studies concerning the effects of drugs. It can also be used to study phenomena that only occur in living subjects, such as metabolic processes and cancer metastasis. Another use for this technology is in translational research, the aim of which is to apply the results of research into individual molecules or cells to medical therapy. In developing this technology, Olympus used knowledge accumulated through its activities as a manufacturer of microscopes and endoscopes, including elemental technologies in the field of molecular and in vivo imaging. |
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The Micro laser scanning microscope was developed by combining the results of NEDO-funded research into the development of a practical endomicroscope with laser scanning microscope technology. |
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Because this technology allows continuous observation of small laboratory animals, it will help to reduce the number of animals used in research experiments. |
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Olympus aims to contribute to society through the advancement of basic biological research and translational research, by developing products based on this technology, and by creating systems suitable for use in humans in the future. |
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Molecular targeting drug: This new class of therapeutic drugs has attracted considerable interest in recent years, especially in the field of cancer treatment. Because they act on specific cells that are involved in diseases, they are reported to cause fewer side-effects than conventional drugs. |
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Detailed Features of the Micro laser Scanning Microscope |
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World’s smallest objective lens — only 1.3mm diameter |
Olympus has developed the world’s smallest ultra-slim microscopic objective lens. Small enough to allow insertion into the body of a small animal, this lens allows observations at total magnifications up to 1,000x. It is based on knowledge gained through a NEDO-funded research program into the development of a practical endo-microscope. |
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On the left: the tip of 0.5mm mechanical pencil,
on the right: the 1.3mm object lens — the world’s smallest |
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Multiple lasers for a wide range of observation methods |
The system is equipped with multiple lasers for a wide range of experimental purposes. There is an argon laser for use with fluorescent proteins, as well as laser light sources in ranges that pass easily through the bodies of small laboratory animals, including red and infra-red. |
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Detailed Features of the In Vivo Fluorescence Observation System |
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New optical system |
The optical system allows highly sensitive in vivo observations of fluorescence signals emitted inside small laboratory animals from outside of their bodies. The 3-D CAD technology used in the system is optimized to provide bright fluorescence images. The glass materials used were carefully selected to allow sensitive fluorescence observation. |
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Rapid adjustment |
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Because the magnification can be adjusted rapidly from micro to macro levels, it is possible to make observations across a wide range of levels. For example, the system could be used at low magnification to obtain an overall image of a small laboratory animal, followed by high-magnification observations of various phenomena, such as blood flows in new capillaries formed in the vicinity of subcutaneous cancer cells. |
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Automatic adjustment of CCD camera and optical system |
To ensure optimal observation at each magnification, the illumination systems are automatically adjusted according to the magnification. Further optimization is possible by entering the name of the fluorescence probes used in the experiment and the observation magnification on the imaging software. |
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