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Microscope device and fluorescent observing method using same

外国特許コード F120006757
整理番号 B115-02WO
掲載日 2012年6月8日
出願国 欧州特許庁(EPO)
出願番号 09812947
公報番号 2325684
公報番号 2325684
出願日 平成21年6月10日(2009.6.10)
公報発行日 平成23年5月25日(2011.5.25)
公報発行日 平成29年2月1日(2017.2.1)
国際出願番号 JP2009060644
国際公開番号 WO2010029799
国際出願日 平成21年6月10日(2009.6.10)
国際公開日 平成22年3月18日(2010.3.18)
優先権データ
  • 特願2008-235795 (2008.9.13) JP
  • 2009WO-JP60644 (2009.6.10) WO
発明の名称 (英語) Microscope device and fluorescent observing method using same
発明の概要(英語) (EP2325684)
A microscope capable of controlling the position and fluorescent recording of an object under observation such as cells is provided with the fluorescent observation method using the microscope.
The microscope 1 comprises: a stage 3 on which the object under observation 2 is placed; an illumination light source 4 for the object under observation 2; an excitation light source 5 for exciting fluorescent light F to the object under observation 2; an image information detecting part 16 for detecting the image information formed with the light T generated at the object under observation 2; a fluorescent image information detecting part 17 for detecting the fluorescent image information formed with fluorescent light F; and a control part 20, which determines the fluorescent observation area of the object under observation 2 based on the dynamic model of the object under observation 2 and its image information entered from the image information detecting part 16, and then obtains the image information of the object under observation 2 entered from the image information detecting part 16 and the fluorescent image information entered from the fluorescent image information detecting part 17 at specified interval within the fluorescent observation area.
特許請求の範囲(英語) [claim1]
1. A microscope suitable for observation of body tissue, comprising: a stage (3) for placing an object under observation (2); a first light source (4) for irradiating illumination light to the object under observation (2); a second light source (5) for irradiating excitation light for exciting fluorescent light to the object under observation (2); an image information detecting part (16) for detecting image information formed with the light generated at the object under observation (2); a fluorescent image information detecting part (17) for detecting image information formed with the fluorescent light generated at the object under observation (2); and a control part (20) for determining a fluorescent observation area of the object under observation (2) based on the image information of the object under observation (2) input from the image information detecting part (16) and for obtaining in-image information of the object under observation (2) input from the image information detecting part (16) in the fluorescent observation area and in-fluorescent image information input from the fluorescent image information detecting part (17),
characterized in that: the control part (20) determines the fluorescent observation area based on: a central position of the fluorescent observation area which is obtained only with help of a dynamic model of the body tissue based on the image information or the in-image information; and a width of the fluorescent observation area which is obtained by an optimum control law minimizing or maximizing an evaluation function exhibiting the efficiency of fluorescent observation, the efficiency being expressed in that the evaluation function is formulated such that the number of times of fluorescent observations are minimized and the number of cells that can be subjected to fluorescent observation are maximized when the width of the fluorescent observation area is obtained by classic control law or modern control law applied to the image information or the in-image information, and then the control part (20) obtains the in-image information and the in-fluorescent image information by moving the stage (3) at each interval of a position within the fluorescent observation area, and the dynamic model is defined as a model representing the body tissue by the spatiotemporal change of at least one parameter selected from the group consisting of position, speed, distribution, type, shape, ionic concentration and molecular concentration of the body tissue.
[claim2]
2. The microscope as set forth in claim 1, characterized in that the classic control law is PID control law and the modern control law is optimum control or sub-optimum control.
[claim3]
3. The microscope as set forth in claim 1, characterized in that the light generated at the object under observation (2) is transmission light from the object under observation (2).
[claim4]
4. The microscope as set forth in claim 1, characterized in that the control part (20) performs feedback control for the motion of the stage (3) based on the image information or the in-image information, wherein the feedback control is performed by PID control law.
[claim5]
5. The microscope as set forth in claim 1, characterized in that the control part (20) is provided with a first light source control part for controlling the first light source (4) and a second light source control part for controlling the second light source (5).
[claim6]
6. The microscope as set forth in claim 1, characterized in that the stage (3) is a two-dimensional or three-dimensional stage for moving the position of the object under observation (2).
[claim7]
7. The microscope as set forth in claim 1, characterized in that the fluorescent image information detecting part (16) has a wavelength selecting means for isolating fluorescent light of one or more wavelengths.
[claim8]
8. The microscope as set forth in claim 1, characterized in that a first pinhole is provided between the second light source and the object under observation (2), and a second pinhole is provided between the fluorescent light and the fluorescent image information detecting part.
[claim9]
9. The microscope as set forth in claim 8, characterized in that a pin-hole drive part is provided for moving and/or rotating the first pinhole or the second pinhole.
[claim10]
10. The microscope as set forth in claim 1, characterized in that an objective lens (6) is provided between the first light source (4) and the object under observation (2), and an objective lens drive part is provided for driving the objective lens (6).
[claim11]
11. The microscope as set forth in claim 1, characterized in that an imaging lens (7) is provided between a light generated at the object under observation (2) and the image information detecting part (16), and an imaging lens drive part is provided for driving the imaging lens (7).
[claim12]
12. The microscope as set forth in claim 1, characterized in that an imaging lens (12) is provided between the fluorescent light and the fluorescent image information detecting part (17), and an imaging lens drive is provided part for driving the imaging lens (12).
[claim13]
13. The microscope as set forth in claim 12, characterized in that an environmental control part (60, 80) is provided, and the environmental control part (60, 80), which houses the object under observation (2), is filled with an ambient gas.
[claim14]
14. The microscope as set forth in claim 13, characterized in that the environmental control part (60, 80) has a housing part (64, 84) capable of housing a plurality of the objects under observation (2).
[claim15]
15. The microscope as set forth in claim 14, characterized in that the environmental control part (60, 80) provides a means for stimulating a body tissue to apply at least one stimulus selected from the group consisting of electrical stimulus, magnetic stimulus, dynamic stimulus, ultrasonic stimulus, thermal stimulus, chemical stimulus and optical stimulus to the body tissue that is the object under observation (2).
[claim16]
16. A fluorescent observation method for determining a fluorescent observation area of an object under observation (2) based on image information of the object under observation (2), using a first light source (4) for irradiating illumination light to the object under observation (2) and a second light source (5) for irradiating excitation light for exciting fluorescent light to the object under observation (2) and obtaining in-image information of an object under observation (2) and in-fluorescent image information of the object under observation (2), characterized in that: the object under observation (2) is body tissue; and the fluorescent observation method comprises: a first step for determining the fluorescent observation area based on: a central position of the fluorescent observation area which is obtained only with help of a dynamic model of the body tissue based on the image information or the in-image information; and a width of the fluorescent observation area which is obtained by an optimum control law minimizing or maximizing an evaluation function exhibiting the efficiency of fluorescent observation, the efficiency being expressed in that the evaluation function is formulated such that the number of times of fluorescent observations are minimized and the number of cells that can be subjected to fluorescent observation are maximized when the width of the fluorescent observation area is obtained by classic control law or modern control law applied to the image information or the in-image information, and a second step for obtaining the in-fluorescent image information by moving the stage (3) at each interval of position within the fluorescent observation area, and wherein the dynamic model is defined as a model representing the body tissue by the spatiotemporal change of at least one parameter selecting from the group consisting of position, speed, distribution, type, shape, ionic concentration and molecular concentration of the body tissue.
[claim17]
17. The fluorescent observation method as set forth in claim 16, characterized in that the classic control law is PID control law and the modern control law is optimum control or sub-optimum control.
[claim18]
18. The fluorescent observation method as set forth in claim 16, characterized in that the in-image information is obtained in the second step.
[claim19]
19. The fluorescent observation method as set forth in any one of claims 17 or 18, characterized in that each of the steps is repeated for a specified number of times at each predetermined position within the fluorescent observation area.
  • 出願人(英語)
  • JAPAN SCIENCE AND TECHNOLOGY AGENCY
  • 発明者(英語)
  • IGARASHI YASUNOBU
  • OBARA TAKESHI
  • DEGUCHI YUKI
  • SUZUKI TAKESHI
  • HASHIMOTO KOICHI
国際特許分類(IPC)
欧州特許分類/主・副
  • G01N021/64P4C
  • G02B021/00M4A7U
  • G02B021/26
  • S02B021/16
指定国 (EP2325684)
Contracting States: AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK TR
参考情報 (研究プロジェクト等) SORST Selected in Fiscal 2005
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