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Measurement device and irradiation device

Foreign code F210010320
File No. E120P08WO
Posted date Feb 1, 2021
Country United States of America
Application number 201816637011
Gazette No. 20200166457
Gazette No. 10837906
Date of filing Aug 9, 2018
Gazette Date May 28, 2020
Gazette Date Nov 17, 2020
International application number JP2018029924
International publication number WO2019031584
Date of international filing Aug 9, 2018
Date of international publication Feb 14, 2019
Priority data
  • P2017-154392 (Aug 9, 2017) JP
  • 2018JP29924 (Aug 9, 2018) WO
Title Measurement device and irradiation device
Abstract According to the present invention, a measurement device includes a light emitting part configured to emit a plurality of spectral lights each including two or more spectra distributed at mutually different frequencies by causing adjacent frequency intervals to be different from each other, a focusing part configured to focus light by causing two or more spectra to overlap in an overlapping region in each of a plurality of different focal point regions of a sample and to be shifted from each other, and a detecting part configured to acquire a signal of fluorescence beats which emits light by interference light beats in each of a plurality of overlapping regions in the sample and includes information of the sample.
Outline of related art and contending technology BACKGROUND OF THE INVENTION
Conventionally, a fluorescence microscope equipped with a confocal optical system (hereinafter referred to as a confocal fluorescence microscope) is known as an optical microscope capable of performing fluorescence imaging (for example, see Patent Document 1).
In a normal optical microscope, a predetermined range of a sample is uniformly irradiated with light. On the other hand, in a confocal optical system, irradiation light emitted from a point light source is focused at one point on the sample by an objective lens. As the irradiation light, laser light having excellent monochromaticity and straightness is used. Also, in the confocal optical system, the pinhole is disposed at a position conjugate to the focal position of the objective lens and therefore only the fluorescence at a position where the sample is focused passes through the pinhole and is detected.
In this manner, in the confocal optical system, the irradiation light is first focused at one point on the sample and the fluorescence from a focal position of the sample passes through the pinhole, whereas the fluorescence from a position other than the focal position is cut out by the pinhole. Accordingly, in the confocal optical system, as compared with a normal optical microscope, the contrast is improved without being affected by stray light from a horizontal side adjacent to a focal point and from a front side and a rear side with respect to a focal plane. As a result, because only information of the focal position of the irradiation light is detected, three-dimensional spatial resolution is provided.
For example, confocal fluorescence microscopes capable of forming clear three-dimensional images as described above are used in many fields including a biotechnology field for the analysis of biological functions using fluorescent proteins and the like. Also, the importance of confocal fluorescence microscopy is expected to increase in the future because of high resolution and quantitative properties.
On the other hand, the confocal fluorescence microscope can only obtain point information of the focal position. Thus, in the confocal fluorescence microscope, it is necessary to relatively scan a focal position of the irradiation light emitted from the point light source inside the sample so that two-dimensional information within a sample surface is imaged. For example, a galvano mirror is known as a scanning device capable of scanning the focal position of irradiation light relatively with respect to a sample as described above. However, even if these scanning devices are used, a process of scanning a wide range at a high speed takes time.
As technology for coping with the above-described situation, a measurement device for causing a discrete spectrum emitted by a point light source to be two-dimensionally dispersed with respect to a measurement sample for each spectrum and acquiring mode-resolved spectra corresponding to measurement points of the measurement sample at one time is disclosed in, for example, Patent Document 2. This measurement device obtains information of a sample by associating position information of a spectrum incident on the sample with a frequency of the spectrum. Thus, an image can be formed without scanning the two-dimensional information within the sample surface.
Scope of claims [claim1]
1. A measurement device, comprising:
a plurality of light sources configured to each emit spectral light including two or more spectra distributed at mutually different frequencies, wherein adjacent frequency intervals that are frequency intervals of adjacent spectra of the spectral light are mutually different;
a dispersing part configured to disperse a plurality of spectral lights emitted from the plurality of light sources in mutually different directions according to each spectrum;
a focusing part configured to focus the spectra specific to the light sources dispersed by the dispersing part at a plurality of different focal points on a sample and cause a plurality of focal points based on one light source to overlap a plurality of focal points based on another light source;
a spatial filtering part configured to focus fluorescence beats including information of the sample on which light is focused by the focusing part and which emits light by interference light beats in each of a plurality of overlapping portions where the focal points on the sample overlap at positions conjugate to the overlapping portions and perform spatial filtering on the fluorescence beats; and
a detecting part configured to acquire a signal of the fluorescence beats on which the spatial filtering has been performed by the spatial filtering part and which has been emitted from the plurality of overlapping portions including the information of the sample.

[claim2]
2. The measurement device according to claim 1, wherein each of the plurality of light sources is an optical frequency comb light source configured to emit spectra in which adjacent frequency intervals which are intervals of frequencies of the spectra adjacent on a frequency axis are equal to each other as the spectral light.

[claim3]
3. The measurement device according to claim 1,
wherein the dispersing part includes a dispersing element configured to perform wavelength dispersion on incident light, and
wherein the dispersing part performs wavelength dispersion on the spectral light emitted from the light source by the dispersing element in a direction differing according to each spectrum.

[claim4]
4. The measurement device according to claim 1,
wherein the plurality of light sources include at least a first light source configured to emit first spectral light in which a frequency interval of the adjacent spectrum is a first adjacent frequency interval and a second light source configured to emit second spectral light in which a frequency interval of the adjacent spectrum is a second adjacent frequency interval, and
wherein a frequency interval between closest adjacent spectra is less than half of the first adjacent frequency interval and half of the second adjacent frequency interval when the first spectral light and the second spectral light are arranged on the same frequency axis.

[claim5]
5. The measurement device according to claim 1, further comprising a control part configured to control a carrier envelope offset frequency or an adjacent frequency interval of spectral light emitted by at least one light source of the plurality of light sources.

[claim6]
6. The measurement device according to claim 5, wherein the spatial filtering part comprises a spatial optical modulator capable of changing a position or a shape of light to be transmitted in accordance with the offset frequency and the adjacent frequency interval of the spectral light controlled by the control part.

[claim7]
7. An irradiation device, comprising:
a plurality of light sources configured to each emit spectral light including two or more spectra distributed at mutually different frequencies, wherein adjacent frequency intervals that are frequency intervals of adjacent spectra of the spectral light are mutually different;
a dispersing part configured to disperse a plurality of the spectral lights emitted from the plurality of light sources in mutually different directions according to each spectrum; and
a focusing part configured to focus the spectra specific to the light sources dispersed by the dispersing part at a plurality of different focal points on a sample and cause a plurality of focal points according to one light source to overlap a plurality of focal points according to another light source.

[claim8]
8. The irradiation device according to claim 7,
wherein the plurality of light sources include at least a first light source configured to emit first spectral light in which a frequency interval of the adjacent spectrum is a first adjacent frequency interval and a second light source configured to emit second spectral light in which a frequency interval of the adjacent spectrum is a second adjacent frequency interval, and
wherein a frequency interval between closest adjacent spectra is less than half of the first adjacent frequency interval and half of the second adjacent frequency interval when the first spectral light and the second spectral light are arranged on the same frequency axis.

[claim9]
9. The irradiation device according to claim 7,
wherein the plurality of light sources simultaneously irradiate irradiation light to focal points on a sample, and
wherein the irradiation light from the light sources mutually interferes at the focal points on the sample.

[claim10]
10. An irradiation device, comprising:
a first light source configured to emit first light having frequency components of a plurality of frequency values which are discrete;
a second light source configured to emit second light having frequency components of a plurality of frequency values which are discrete and different from the first light; and
a dispersing and focusing part configured to disperse the first light and the second light and focus the first irradiation light and the second irradiation light so that parts of both a first irradiation region of first irradiation light having a frequency component of a first frequency value according to the first light and a second irradiation region of second irradiation light having a frequency component of a second frequency value according to the second light overlap,
wherein the first irradiation light and the second irradiation light are simultaneously irradiated so that a difference between the first frequency value and the second frequency value is less than or equal to a difference between the first frequency value of the first light and a frequency value adjacent thereto.

[claim11]
11. A measurement device, comprising:
a light emitting part configured to emit a plurality of spectral lights each including two or more spectra distributed at mutually different frequencies, wherein adjacent frequency intervals that are frequency intervals of adjacent spectra in each of the plurality of the spectral lights are mutually different;
a dispersing part configured to disperse the plurality of the spectral lights emitted from the light emitting part in mutually different directions according to each spectrum;
a focusing part configured to focus the spectra dispersed by the dispersing part at a plurality of different focal points on a sample and cause a plurality of focal points based on one of the spectral lights to overlap a plurality of focal points based on another of the spectral lights; and
a detecting part configured to acquire a signal of fluorescence beats including information of the sample on which light is focused by the focusing part and which emits light by interference light beats in each of a plurality of overlapping regions where the focal points on the sample overlap.

[claim12]
12. The measurement device according to claim 11, wherein the light emitting part has a plurality of light sources configured to each emit two of the spectral lights having the adjacent frequency intervals which are mutually different.

[claim13]
13. The measurement device according to claim 11, further comprising a spatial filtering part configured to focus fluorescence beats including information of the sample on which light is focused by the focusing part and which emits light by interference light beats in each of a plurality of overlapping regions where the focal points on the sample overlap at positions conjugate to the overlapping regions and perform spatial filtering on the fluorescence beats,
wherein the detecting part acquires a signal of the fluorescence beats on which the spatial filtering has been performed in the spatial filtering part.

[claim14]
14. The measurement device according to claim 1 or 11, wherein the detecting part acquires phase information of the fluorescence beats.

[claim15]
15. An irradiation device, comprising:
a light emitting part configured to emit spectral light including two or more spectra distributed at mutually different frequencies, wherein adjacent frequency intervals that are frequency intervals of adjacent spectra of the spectral light are mutually different;
a dispersing part configured to disperse a plurality of spectral lights emitted from the light emitting part in mutually different directions according to each spectrum; and
a focusing part configured to focus the spectra specific to light sources dispersed by the dispersing part at a plurality of different focal points on a sample and cause a plurality of focal points based on one light source to overlap a plurality of focal points based on another light source.

[claim16]
16. A measurement device, comprising:
a plurality of light sources configured to each emit spectral light including two or more spectra distributed at mutually different frequencies, wherein adjacent frequency intervals that are frequency intervals of adjacent spectra of the spectral light are mutually different;
a dispersing part configured to disperse a plurality of spectral lights emitted from the plurality of light sources in mutually different directions according to each spectrum;
a focusing part configured to focus the spectra specific to the light sources dispersed by the dispersing part at a plurality of different focal points on a sample and cause a plurality of focal points based on one light source to overlap a plurality of focal points based on another light source;
a detecting part configured to acquire a signal of the fluorescence beats including information of the sample on which light is focused by the focusing part and which emits light by interference light beats in each of a plurality of overlapping portions where the focal points on the sample overlap.
  • Inventor, and Inventor/Applicant
  • YASUI TAKESHI
  • IWATA TETSUO
  • MIZUTANI YASUHIRO
  • MINAMIKAWA TAKEO
  • MIZUNO TAKAHIKO
  • HASE EIJI
  • YAMAMOTO HIROTSUGU
  • JAPAN SCIENCE AND TECHNOLOGY AGENCY
IPC(International Patent Classification)
Reference ( R and D project ) ERATO MINOSHIMA Intelligent Optical Synthesizer AREA
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