JP2005098808A - Biological information detecting apparatus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a biological information detecting apparatus advantageous for accurately and efficiently examining the effects of environmental factors, such as chemical substances drugs, and stress to biological materials. <P>SOLUTION: The biological information detecting apparatus is provided with an installation part 2 capable of installing a holding part 1 for holding a biomaterial 12; a shape detecting means 3 for detecting information on the shape of the biomaterial 12 held by the holding part 1; and a light emission state detecting means 4 for detecting information on the state of light emission at the biomaterial 12 held by the holding part 1. The shape-detecting means 3, for example, can image a visible image of the biomaterial 12. The light emission state detecting means 4 can image a fluorescent image of the biomaterial 12. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

The present invention relates to a biological information detection apparatus capable of examining the influence of environmental factors such as chemical substances, pharmaceuticals, and stress on biological materials such as biological tissues, cells, eggs, DNA, and antibodies.

  At present, there are about 100,000 chemical substances frequently used in daily life in Japan, 4 million kinds of mixtures thereof, and several million kinds of new chemical substances are permitted to be used every year. It has begun to be pointed out that the use of these chemicals has an unexpected impact on ecosystem destruction and human health. Recently, when considering the effects of chemical substances on humans, the existence of people who are easily affected by chemical substances (so-called cross-sensitive groups) is beginning to be highlighted.

  Therefore, in order to evaluate the safety of chemical substances, pharmaceuticals, etc., chemical substances, pharmaceuticals, etc. can be obtained using cells such as E. coli, yeast, cultured human cells, fertilized eggs or early embryos of fish such as medaka and zebrafish. There is a demand for the development of an apparatus that can evaluate the influence and can easily and quickly capture and analyze image information in a living body. Examples of such an apparatus include a fluorescence microscope and a scanning probe microscope. However, since these are very expensive, it is not an apparatus that anyone can operate easily and quickly.

Conventionally, there are reports relating to the following non-patent documents 1 to 4 as fluorescence imaging and analysis techniques of biomolecules (nucleic acid molecules and complexes thereof) using fluorescence in situ hybridization and a fluorescence microscope. Further, as a visualization technique based on scanning probe microscopy, there are the following reports related to the following non-patent documents 5 to 10. Furthermore, there is a technique according to Patent Document 1 as a technique for incorporating a three-dimensional stage into an optical microscope, forming an image of a sample from a plurality of directions, and displaying the image on a television monitor.
Manuelidis, L et al., 1982, J. MoI. Cell. Biol. 95, 619 Lawrence, C.I. A. Et al., 1988, Cell, 52, 51 Richter, P.A. Et al., 1990, Science 247, 64. Heng, H .; H. Q. Et al., 1992, Proc. Natl. Acad. Sci. USA89, 9509 Karrasch, S .; Et al., 1993, Biophysical, J. et al. , 65, 2437 Hansma, H .; G. Et al., 1993, Nucleic Acids Research 21,505. Bustamante, C.I. Et al., 1992, Biochemistry 31,22. Lyubchenko, Y, L .; Et al., 1992, J. Am. Biomol, Struct, and Dyn. , 10,589 Allison, D.C. P. Et al., 1992, Proc. Natl. Acad. Sci. USA89,10129 Zenhausen, F, et al., 1992, J. Am. Struct. Biol. 108,69 JP 7-333519 A

  However, according to the above-described technique, there is a limit in accurately and efficiently examining the influence of environmental factors such as chemical substances, pharmaceuticals, and stress on biological materials.

  The present invention has been made in view of the above circumstances, and provides a biological information detection device that is advantageous for accurately and efficiently examining the influence of environmental factors such as chemical substances, pharmaceuticals, and stress on biological materials. Is the subject.

  The biological information detection apparatus according to aspect 1 includes an installation unit capable of installing a holding unit that holds a biological material, a shape detection unit that detects information related to the shape of the biological material held by the holding unit, and a holding unit that holds the information. And a light emission state detecting means for detecting information on the light emission state in the biomaterial.

  When environmental factors such as chemical substances, pharmaceuticals, and stress are applied to the biomaterial, changes may occur inside the biomaterial. Therefore, it is possible to examine the influence of environmental factors such as chemical substances, pharmaceuticals, and stress on the biomaterial based on the information on the light emission state inside the biomaterial.

  However, the light-emitting part of the biomaterial is generally a part affected by the environmental factors described above and is localized, so the affected part corresponds to which part of the biomaterial. Whether or not to do so is not necessarily clear only by the state of light emission in the biomaterial.

  Therefore, according to the biological information detection apparatus according to aspect 1, information related to the shape of the biological material detected by the shape detection unit is detected. Then, based on the information on the shape of the biomaterial detected by the shape detection means and the information on the light emission status in the biomaterial detected by the light emission status detection means, the portion that emits light in the biomaterial is the shape of the biomaterial. It is grasped in which position it exists. This can be done by image processing or the naked eye of the operator.

  In other words, it is possible to accurately grasp the positional relationship between the portions of the biomaterial that emit light locally with respect to the shape of the biomaterial. As a result, the light-emitting part in the biomaterial can be accurately grasped. Therefore, it is possible to accurately grasp which part of the biomaterial is affected by environmental factors such as chemical substances, pharmaceuticals, and stress.

  According to the present invention, the biomaterial includes a material constituting a living organism, an effluent discharged from the living organism, and the like. Living organisms include animals and plants. Animals include mammals, fish and the like. The biomaterial may be alive or non-living. Examples of the biomaterial include, but are not limited to, at least one of biological tissues, cells, eggs, DNA, and antibodies. The biomaterial can carry or be capable of carrying a fluorescent compound. Examples of the fluorescent compound include at least one of fluorescent protein, Texas red, fluorescein isothiocyanate (FITC), fluorescein, rhodamine, coumarin, and cascade blue, but are not limited thereto.

  According to the biological information detection apparatus according to aspect 2, the shape detection unit detects information related to the shape of the biological material by capturing a visible image of the biological material held in the holding unit. Thus, if the visible image of a biomaterial is imaged, the information regarding the shape of a biomaterial can be detected easily.

  According to the biological information detection apparatus according to aspect 3, the shape detection unit captures an illumination unit that applies visible light to the biological material held by the holding unit, and an imaging that captures the biological material to which the visible light of the illumination unit is applied. And a portion. When a visible image of a biological material is captured while applying visible light to the biological material held by the holding unit in this way, the clarity of the visible image is improved, and information on the shape of the biological material (such as an outline) ) Can be easily detected. As the visible light, white illumination light can be exemplified, but the present invention is not limited to this, and in some cases, colored illumination light may be used.

  According to the biological information detection apparatus according to aspect 4, at least one of the shape detection unit and the light emission state detection unit includes a lens system disposed between the imaging unit and the holding unit. To do. If the focal length of the lens system is variable, a visible image of the biomaterial can be captured more clearly by focusing, which is advantageous for detecting information (contour etc.) on the shape of the biomaterial.

  According to the biological information detection apparatus according to aspect 5, the light emission state detection unit includes an excitation light source that emits light in the biological material by applying excitation light to the biological material held in the holding unit, and a biological material that emits light. And an imaging unit for imaging. In this way, if the biological material is imaged in a state where light is emitted inside the biological material by applying excitation light to the biological material by the excitation light source, the clarity of imaging by the light emission state detecting means is improved, and The light emitting site can be easily detected inside. The emission can be fluorescence.

  Therefore, the biomaterial carries or can carry a fluorescent compound, and as described above, the fluorescent compound is one of fluorescent protein, Texas red, fluorescein isothiocyanate (FITC), fluorescein, rhodamine, coumarin, cascade blue. At least one of these can be exemplified. A fluorescent compound is a compound that can emit fluorescence when excited. A fluorescent compound can be introduced into and supported on a biological material by an injection operation using an injection needle or the like.

According to the biological information detection apparatus according to aspect 6, the shape detection unit images the illuminating unit that applies visible light to the biomaterial held in the holding unit, and the biomaterial to which visible light from the illuminating unit is applied. And 1 imaging unit,
The light emission state detection means includes an excitation light source that emits light inside the biological material by applying excitation light to the biological material held by the holding unit, and a second imaging unit that images the emitted biological material. And
In a state where the excitation light is applied to the biological material held by the holding unit and is emitted inside the biological material, the shape detecting unit captures the emitted biological material with the second imaging unit of the emission state detecting unit. The first imaging unit is provided with a control unit that performs an operation so as to image a biomaterial.

  Even if the biomaterial emits light, the light emission state may fluctuate with time. Even if the biomaterial emits light, the biomaterial may deteriorate when it receives illumination light. Therefore, after the luminescent biomaterial is imaged by the second imaging unit of the light emission state detection unit, an operation is performed so that the biomaterial is imaged by the first imaging unit of the shape detection unit. In this case, since the biomaterial is imaged by the first imaging unit of the shape detection unit after the illuminating biomaterial is imaged by the first imaging unit of the shape detection unit, the light emission state of the biomaterial varies with time. Easy to deal with. In addition, since the biomaterial captures the light emission state of the biomaterial before receiving the illumination light, it is advantageous to avoid the deterioration of the light emission state of the biomaterial due to the illumination light and improve the detection accuracy. It will be advantageous.

  It is preferable that the focal length related to the shape detection unit for the biomaterial and the focal length related to the light emission state detection unit for the biomaterial are the same. In this case, the visible image and the fluorescent image are images having the same size and the same depth of focus, and the visible image and the fluorescent image are easily aligned. Therefore, it becomes easy to superimpose the visible image and the fluorescent image or to compare the visible image and the fluorescent image side by side. In other words, the contour of the visible image and the inside of the fluorescent image can be accurately overlapped or compared side by side. Therefore, it becomes easy to specify which part of the biomaterial is the part emitting fluorescence in the fluorescent image.

  According to the biological information detection apparatus according to aspect 7, the shape detection unit and the light emission state detection unit are arranged at an interval, and the shape of the holding unit is detected between the shape detection unit and the light emission state detection unit. And holding unit moving means for moving relative to the means and the light emission state detecting means. In this case, the shape detecting means relatively moves the holding unit between the shape detecting means and the light emission state detecting means, so that information on the shape of the biomaterial can be detected by the shape detecting means, and Information on the light emission state inside can be detected by the light emission state detection means.

  In general, the shape detection unit and the light emission state detection unit holding unit are fixed, and the holding unit is moved relative to the shape detection unit and the light emission state detection unit. In some cases, the holding unit may be fixed, and the shape detection unit and the light emission state detection unit may be moved relative to the holding unit.

  According to the biological information detection apparatus according to aspect 8, the shape detection unit and the light emission state detection unit are arranged to face each other so that the holding unit is positioned between the shape detection unit and the light emission state detection unit. It is characterized by. In this case, the moving distance of the holding part can be reduced or eliminated. Detection by the shape detection unit and detection by the light emission state detection unit can be performed in a short time. Furthermore, since the shape detection means and the light emission state detection means are arranged to face each other, it is advantageous for downsizing.

  According to the biological information detection apparatus according to aspect 9, the biological material is at least one of biological tissues, cells, eggs, DNA, and antibodies. The influence of environmental factors such as chemical substances, pharmaceuticals, and stress on these biological tissues, cells, eggs, DNA, and antibodies can be examined.

  According to the biological information detection apparatus according to aspect 10, the biological material carries or can carry a fluorescent compound, and the fluorescent compound is fluorescent protein, Texas Red, fluorescein isothiocyanate (FITC), fluorescein, rhodamine, It is at least one of coumarin and cascade blue. In this case, the inside of the biomaterial can be effectively fluorescently emitted by the fluorescent compound. For this reason, the influence which environmental factors, such as a chemical substance, a pharmaceutical, and stress, have on the inside of a biomaterial can be investigated based on fluorescence emission.

  According to the present invention, based on the information related to the shape of the biological material detected by the shape detection means and the information related to the light emission status in the biological material detected by the light emission status detection means, the target portion of the biological material is determined. Can be positioned with respect to the shape of the biomaterial. Therefore, it is possible to provide a biological information detection apparatus that is advantageous for examining the influence of environmental factors such as chemical substances, pharmaceuticals, and stress on the inside of the biological material.

(Embodiment 1)
Embodiment 1 of the present invention will be specifically described with reference to FIGS. The biological information detection apparatus according to the present embodiment is an apparatus that can observe the influence of chemical substances on biological materials such as eggs and fry using biological materials such as transparent eggs of fish. In other words, a chemical substance is introduced as a fluorescent protein promoter into a biological material such as a transparent fish egg, and the whole image of the egg is informatized with a visible image on how the biological material is affected by the introduced chemical substance. At the same time, changes in the fluorescence characteristics emitted by the fluorescent protein due to the introduced chemical substance are converted into information using a fluorescent image, and the two pieces of image information of the visible image and the fluorescent image are superimposed or compared side by side, thereby allowing chemical substances, etc. It is intended to measure the effects over time.

  As shown in FIG. 1, the biological information detection apparatus according to the present embodiment is basically installed in an installation unit 2 that detachably installs a holding unit 1 that holds a biological material 12, and an installation unit 2. The shape detection means 3 capable of detecting the shape of the biological material 12 held by the holding unit 1, particularly the contour of the shape of the biological material 12, and the biological material held by the holding unit 1 installed in the installation unit 2 12 is provided with a light emission state detection means 4 for detecting information on the light emission state inside.

  The holding part 1 is also called a well, and has a plurality of recesses 10 arranged vertically and horizontally as shown in FIGS. The recess 10 can hold the biomaterial 12. As the biological material 12, biological tissue, cells, eggs, DNA, antibodies, etc., specifically, cells such as Escherichia coli, yeast, human cultured cells, fertilized eggs and early embryos of fish such as medaka and zebrafish are used. However, it is not limited to these. When an environmental factor such as a chemical substance, a medicine, or stress is applied to the biomaterial 12 represented by these, depending on the internal site of the biomaterial 12, the fluorescent property that the biomaterial 12 emits changes depending on the influence of the environmental factor. There are things to do. In this case, the influence of environmental factors on the biomaterial 12 can be grasped by examining the fluorescence characteristics inside the biomaterial 12. In addition, it is preferable to hold | maintain the biomaterial 12 in the recessed part 10 of the holding part 1 so that it may not move.

  As shown in FIG. 1, the installation part 2 installs the holding | maintenance part 1 so that attachment or detachment is possible, and it can move to a horizontal two-dimensional direction and a height direction. The installation unit 2 for installing the holding unit 1 is three-dimensionally arranged in the X-axis direction (first direction; one direction in the two-dimensional horizontal direction) and the Y-axis direction (second direction; the other direction in the two-dimensional horizontal direction). 1 is provided with a holding unit moving means 5 for moving in the Z-axis direction (third direction; height direction).

  The holding unit moving means 5 includes an X-axis stage 50 (first stage) that moves the setting unit 2 together with the holding unit 1 in the X-axis direction, and a Y-axis stage that moves the setting unit 2 together with the holding unit 1 in the Y-axis direction. 56 (second stage) and a Z-axis stage 70 (third stage) that moves the installation unit 2 in the Z-axis direction together with the holding unit 1.

  As shown in FIG. 1, the X-axis stage 50 includes a first movable body 51, an X-axis motor 52 (first motor) held by the first movable body 51, and the X-axis motor 52 rotated by the X-axis motor 52. And an X-axis screw shaft 53 that functions as a movable auxiliary element that holds the holding portion 1 in a state of being extended in the direction and screwed into the female screw portion 2 a of the installation portion 2. The X-axis screw shaft 53 is rotatably held on the first movable body 51 by the shaft support 54. When the X-axis motor 52 rotates, the X-axis screw shaft 53 rotates around its axis, and the installation unit 2 moves forward and backward in the X-axis direction together with the holding unit 1.

  The Y-axis stage 56 is rotated by the Y-axis motor 57 (second motor) held by the second movable body 72, and extends in the Y-axis direction (vertical direction shown in FIG. 1). A Y-axis screw shaft 59 that functions as a movable auxiliary element that holds the support portion 58 in a state of being screwed into the female screw portion 58a of the support portion 58 of the first movable body 51, and the first movable body 51 is guided in the Y-axis direction. And a guide portion 66 that is a guide shaft extending in the Y-axis direction. When the Y-axis motor 57 rotates, the Y-axis screw shaft 59 rotates about its axis, and the first movable body 51 moves forward and backward in the Y-axis direction together with the holding unit 1 and the installation unit 2.

  As shown in FIG. 1, the Z-axis stage 70 is rotated by a Z-axis motor 71 (third motor) held by a base 69 provided in a housing (not shown) via a bracket 69 c and the Z-axis motor 71. A Z-axis screw shaft 74 extending in the Z-axis direction and functioning as a movable auxiliary element that holds the second support portion 73 in a state of being screwed into the female screw portion 73a of the second support portion 73 of the second movable body 72; , And a shaft support 75 that rotatably supports the Z-axis screw shaft 74. When the Z-axis motor 71 rotates, the Z-axis screw shaft 74 rotates around its axis, and the second movable body 72 together with the first movable body 51, the holding unit 1 and the installation unit 2 in the Z-axis direction (height direction). ) Go up and down. In this way, the holding unit 1 can move in the three-dimensional direction.

  As shown in FIG. 1, the shape detection means 3 detects the shape of the biomaterial 12 by taking a visible image of the biomaterial 12 held by the holding unit 1, and in particular, the biomaterial 12. Information (contour) relating to the shape of the object is detected. The shape detecting means 3 includes a first extending barrel 30 that extends in one direction and that functions as a first optical path forming member for forming light, and a biological material that is held by the holding portion 1 on the installation portion 2. 12 is used to capture a visible image of the biological material 12 to which the white illumination light 36 from the illumination unit 31 is applied and the illumination unit 31 that applies the white illumination light 36 that is visible light (white light: wavelength 300 to 900 nanometers). A first imaging unit 32 formed by a CCD camera and a first lens system 33 disposed between the first imaging unit 32 and the installation unit 2 are provided.

  The first imaging unit 32 is for capturing a visible image of the biomaterial 12 held by the holding unit 1 on the installation unit 2, and is provided on the base end side (upper end side) of the first extension barrel 30. It has been. The first lens system 33 is provided in the first extension barrel 30 and is disposed relatively to the first imaging lens 34 disposed on the first imaging unit 32 side and relatively to the holding unit 1 side. And a first objective lens 35 provided in series with the first imaging lens 34. The first lens system 33 has a variable focal length and imaging magnification. Therefore, the distance between the first objective lens 35 and the holding unit 1 on the installation unit 2 can be adjusted.

  The illumination unit 31 is provided on the distal end side (lower end side) of the first extension barrel 30 so as to be positioned in the vicinity of the biomaterial 12 held by the holding unit 1. It is provided so as to make one round of rotation continuously. As a result, the white illumination light 36 can be uniformly applied to the biomaterial 12 held in the recess 10 of the holding unit 1, and as a result, a visible image of the biomaterial 12 held in the recess 10 of the holding unit 1 is first displayed. Good imaging can be performed by the imaging unit 32. As shown in FIG. 1, when the first imaging unit 32 captures a visible image of the biomaterial 12 held in the holding unit 1, the first imaging unit 32, the first extension barrel 30, The one imaging lens 34, the first objective lens 35, and the holding unit 1 are arranged in series.

  As shown in FIG. 1, the light emission state detection means 4 is arranged in parallel with the shape detection means 3, and by capturing a fluorescent image of the biological material 12 held by the holding unit 1, the biological material is obtained. The light emission state (internal state) in 12 is detected. The light emission state detection means 4 includes a second extension barrel 40 extending in one direction that forms a cylindrical shape that functions as a second optical path forming member for forming an optical path, and an extension extending in a direction intersecting the second extension barrel 40. An excitation light source 42 that applies excitation light 49 to the biological material 12 that is provided in the setting unit 41 and is held by the holding unit 1, and a biological material that emits light when the excitation light 49 projected from the excitation light source 42 is applied thereto 12 is provided with a second imaging unit 43 formed by a CCD camera for imaging 12 and a second lens system 44 provided in the second extension barrel 40.

  The second extension barrel 40 is provided in parallel to the first extension barrel 30 with a dimension L apart from the first extension barrel 30 so as to be independent of the first extension barrel 30. The second lens system 44 is provided so that its focal length is variable. That is, the distance between the second objective lens 46 and the holding unit 1 on the installation unit 2 is variable.

  The wavelength of the excitation light 49 from the excitation light source 42 can be appropriately selected according to the color of fluorescent light emitted from the biological material 12. For example, when the fluorescence emission color is purple or green yellow, the wavelength of the excitation light 49 of the excitation light source 42 is 400 to 435 nanometers, and when the fluorescence emission color is green blue or orange, the excitation light 49 of the excitation light source 42 is used. When the fluorescent light emission color is green or reddish purple, the excitation light 49 of the excitation light source 42 has a wavelength of 500 to 560 nanometers, and when the fluorescent light emission color is yellow or blue, excitation occurs. When the wavelength of the excitation light 49 of the light source 42 is 580 to 595 nanometers and the fluorescence emission color is purple red, the wavelength of the excitation light 49 of the excitation light source 42 can be 750 to 800 nanometers. However, the wavelength of the excitation light 49 of the excitation light source 42 is not limited to these.

  The second imaging unit 43 is for capturing a fluorescent image of the biomaterial 12 held in the recess 10 of the holding unit 1, and is provided on the base end side (upper end side) of the second extension barrel 40. Yes. A beam splitter 47 that functions as an optical path forming member is provided in the extended portion 41 in the second extension barrel 40 so as to face the excitation light source 42 and the second objective lens 46. Further, a filter 48 that selects the wavelength of the excitation light 49 from the excitation light source 42 and transmits only the excitation light 49 having the selected wavelength is disposed between the beam splitter 47 and the excitation light source 42. Yes. The second lens system 44 is connected in series with the second imaging lens 45 relatively disposed on the second imaging unit 43 side and in series with the second imaging lens 45 so as to be relatively disposed on the holding unit 1 side. And a second objective lens 46 provided.

  As shown in FIG. 2, when the second imaging unit captures a fluorescent image of the biomaterial 12 held in the holding unit 1, the second imaging unit 43 of the light emission state detection unit 4, 2 The extension barrel 40, the second imaging lens 45, the second objective lens 46, and the holding unit 1 are arranged in series. The second lens system 44 has a variable focal length. Therefore, the distance between the second objective lens 46 and the holding unit 1 on the installation unit 2 can be adjusted.

  The first imaging unit 32 and the second imaging unit 43 are connected to the image processing unit 100 of the control unit 101. The image processing unit 100 creates a visible image by image processing based on the signal from the first imaging unit 32, and creates a fluorescent image by image processing based on the signal from the second imaging unit 43.

  Add explanation when using. In this case, the fluorescent compound is introduced and supported in the biomaterial 12 by an injection operation. The fluorescent compound can be at least one of fluorescent protein, Texas red, fluorescein isothiocyanate (FITC), fluorescein, rhodamine, coumarin, and cascade blue. Environmental factors such as chemical substances, pharmaceuticals, and stress are given to the biomaterial 12, and specific parts of the biomaterial 12 may fluoresce depending on environmental factors such as chemical substances, pharmaceuticals, and stress.

  In this way, the biological material 12 carrying the fluorescent compound is held in the recess 10 of the holding unit 1, and the holding unit 1 is installed in the installation unit 2. In a state where the holding unit 1 holding such a biomaterial 12 is installed in the installation unit 2, the X-axis stage 50, the Y-axis stage 56, and the Z-axis stage 70 are appropriately driven to align the holding unit 1, A visible image capturing step and a fluorescence image capturing step are performed on the biomaterial 12.

  According to this visible image capturing step, the biological material 12 of the holding unit 1 is disposed below the first objective lens 35 of the shape detecting means 3 as shown in FIG. Then, the illumination unit 31 is illuminated, and the biomaterial 12 is illuminated with the white illumination light 36 from around the biomaterial 12 held in the recess 10 of the holding unit 1. In this way, a visible image of the biological material 12 is captured by the first imaging unit 32 of the shape detection unit 3 in a state where the biological material 12 is illuminated with the white illumination light 36 of the illumination unit 31. In this case, since the white illumination light 36 has light of many wavelengths, it is advantageous for obtaining a visible image clearly. The imaging magnification and focus of the visible image are basically set by the focal length of the first lens system 33.

  Further, according to the fluorescence image capturing process shown in FIG. 2, the excitation light 49 from the excitation light source 42 of the light emission state detection means 4 is transmitted through the filter 48 and is directed toward the biological material 12 of the holding unit 1 by the beam splitter 47. The reflected light is reflected at an angle (90 degrees), and the excitation light 49 is applied to the biomaterial 12 in the recess 10 of the holding unit 1. As a result, partial fluorescence is generated inside the biomaterial 12. In this state, a fluorescent image of the biomaterial 12 that emits fluorescence is captured by the second imaging unit 43 of the light emission state detection unit 4. The magnification and focus of the fluorescent image are basically set by the focal length of the second lens system 44.

  According to the present embodiment, the focal length of the first lens system 33 related to the shape detection unit 3 and the focal length of the second lens system 44 related to the light emission state detection unit 4 are the same. The imaging magnification by the first lens system 33 and the imaging magnification by the second lens system 44 related to the light emission state detection unit 4 are the same. Therefore, the visible image and the fluorescent image have the same size and the same depth of focus, and it is easy to superimpose the visible image and the fluorescent image or to compare the visible image and the fluorescent image side by side. Accordingly, the contour of the visible image and the inside of the fluorescent image can be accurately superimposed, or the visible image and the fluorescent image can be compared side by side. Thus, since the relationship between the fluorescent light emitting portion of the fluorescent image and the whole image of the biological material 12 is specified, the fluorescent light emitting portion of the biological material 12 is any portion of the biological material 12. It is advantageous to specify whether or not.

  According to the present embodiment, the visible image capturing step can be performed on the same biomaterial 12 after performing the fluorescent image capturing step. In this case, for the same biomaterial 12 on the holding unit 1, after performing a fluorescence image imaging process of capturing a fluorescent image with the second imaging unit 43, the installation unit 2 is dimensioned in the X-axis direction by the holding unit moving means 5. The visible image capturing step of capturing the visible image of the biomaterial 12 on the holding unit 1 with the first imaging unit 32 can be performed after the L is moved and moved.

  Alternatively, for the same biomaterial 12 on the holding unit 1, after performing a visible image imaging process in which a visible image is captured by the first imaging unit 32, the holding unit moving unit 5 moves the installation unit 2 in the X-axis direction by the dimension L. After moving and moving, a fluorescence image imaging step of capturing the fluorescence image of the biomaterial 12 on the holding unit 1 with the second imaging unit 43 may be performed.

  According to this embodiment, the holding part 1 has a plurality of recesses 10. For this reason, after performing the fluorescence image capturing process for all of the biomaterials 12 held in the plurality of recesses 10, the visible image capturing process may be performed for all of the biomaterials 12. Alternatively, after performing the visible image capturing process for all of the biomaterials 12, the fluorescent image capturing process may be performed for all of the biomaterials 12.

  By the way, even when the biomaterial 12 emits fluorescence, if the state of fluorescence emission is temporally reduced or if the white illumination light 36 is applied to the biomaterial 12 emitting fluorescence, the biomaterial 12 fluorescence emission may deteriorate. It is preferable to avoid such an influence. Therefore, it is preferable to perform the visible image capturing step after performing the fluorescent image capturing step on the same biomaterial 12 on the holding unit 1. As described above, it is preferable to execute the fluorescence image capturing process with priority over the visible image capturing process. That is, if the visible image capturing process is performed after the fluorescent image capturing process is performed, the biomaterial 12 in the fluorescent image capturing process has not yet received the white illumination light 36 from the illumination unit 31. Deterioration of fluorescence emission is suppressed, and an advantage that a fluorescent image can be favorably taken is obtained.

  By the way, when environmental factors such as chemical substances, pharmaceuticals, and stress are given to the biomaterial 12 carrying the fluorescent compound, a change in fluorescence emission may occur inside the biomaterial 12. For this reason, it is required to examine the influence of environmental factors such as chemical substances, pharmaceuticals, and stress on the inside of the biomaterial 12. Therefore, according to the present embodiment, the fluorescent material luminescent biomaterial 12 is imaged by the second imaging unit 43 of the luminescence status detection means 4 and a fluorescent image of the biomaterial 12 (information regarding the luminescence status inside the biomaterial 12). Get. For this reason, the internal condition of the biomaterial 12 is grasped based on the fluorescence image. Therefore, it is possible to examine the influence of environmental factors such as chemical substances, pharmaceuticals, and stress on the inside of the biomaterial 12.

  However, it is not always clear which part of the biomaterial 12 corresponds to which part of the biomaterial 12 corresponds to the portion of the biomaterial 12 that emits fluorescence. Therefore, according to the present embodiment, a visible image of the biomaterial 12 is captured by the first imaging unit 32 of the shape detection unit 3. The contour relating to the shape of the biomaterial 12 held by the holding unit 1 can be detected from the visible image.

  FIG. 5 shows a visible image 32 x captured by the first imaging unit 32 of the shape detection unit 3. FIG. 6 shows a fluorescent image 43 x captured by the second imaging unit 43 of the light emission state detection unit 4.

  A visible image 32x (contour 32m regarding the shape of the biological material 12) captured by the first imaging unit 32 of the shape detection unit 3 and a fluorescent image 43x (biological material) detected by the second imaging unit 43 of the light emission state detection unit 4 12), the position of the light emitting portion 43m inside the biomaterial 12 with respect to the contour 32m of the biomaterial 12 is accurately identified.

  In other words, the positional relationship of the portion 43m that emits light inside the biomaterial 12 with respect to the outline 32m of the biomaterial 12 is accurately identified. As a result, a site emitting light within the biomaterial 12 is identified. Therefore, it is possible to accurately grasp which part of the biomaterial 12 (organ etc.) affects environmental factors such as chemical substances, pharmaceuticals, and stress.

  In this case, the visible image 32x shown in FIG. 5 captured by the first imaging unit 32 of the shape detection unit 3 and the fluorescent image 43x shown in FIG. 6 detected by the second imaging unit 43 of the light emission state detection unit 4 are obtained. By superimposing by the image processing, it is possible to accurately grasp the information regarding the light emission state inside the biomaterial 12.

  Alternatively, the visible image 32x shown in FIG. 5 captured by the first imaging unit 32 of the shape detection unit 3 and the fluorescence image 43x shown in FIG. 6 detected by the second imaging unit 43 of the light emission state detection unit 4 are obtained. You may decide to compare side by side by image processing.

  According to the present embodiment, as described above, the excitation light 49 projected from the excitation light source 42 is applied to the biomaterial 12 to cause the biomaterial 12 to fluoresce inside the biomaterial 12, thereby causing the biomaterial 12 emitting fluorescence to be emitted. An image is taken by the second imaging unit 43. For this reason, the clarity of imaging of the fluorescent image is improved, and it is possible to contribute to easily detecting the light emitting site in the biomaterial 12.

  According to the present embodiment, the shape detection unit 3 and the light emission state detection unit 4 are arranged with an interval (dimension L) therebetween, and further, the holding unit is provided between the shape detection unit 3 and the light emission state detection unit 4. A holding unit moving means 5 for moving 1 relative to the shape detecting means 3 and the light emission state detecting means 4 is provided. For this reason, the holding part 1 holding the biomaterial 12 can be relatively moved in the X-axis direction and the Y-axis direction between the shape detection unit 3 and the light emission state detection unit 4. Therefore, the visible image of the biological material 12 held in the holding unit 1 can be imaged by the first imaging unit 32 of the shape detecting unit 3, and the light emission state inside the biological material 12 can be detected by the light emission state detecting unit 4. Images can be taken by the second imaging unit 43.

(Embodiment 2)
FIG. 7 shows a second embodiment. This embodiment has basically the same configuration as that of the first embodiment described above, and basically, parts having the same functions are denoted by common reference numerals. According to the present embodiment, the holding unit 1 that holds the biological material 12 is formed of a transparent material (transparent resin, transparent glass, or the like) that can transmit visible light. As shown in FIG. 7, the shape detection unit 3 and the light emission state detection unit 4 are arranged in the Z-axis direction (height direction) so that the holding unit 1 is positioned between the shape detection unit 3 and the light emission state detection unit 4. Are arranged opposite to each other.

  As shown in FIG. 7, the shape detection unit 3 is positioned below the holding unit 1, and the light emission state detection unit 4 is arranged side by side in the Z-axis direction so as to be positioned above the holding unit 1. Accordingly, as shown in FIG. 7, in the Z-axis direction (height direction), on the same axis line, from the top to the bottom, the second imaging unit 43, the second extension barrel 40, and the second image formation of the light-emission state detecting means 4. The lens 45, the beam splitter 47, the second objective lens 46, and the holding unit 1 are arranged in series, and further, the first objective lens 35, the first imaging lens 34, the first extension barrel 30, and the first imaging unit 32. Are arranged in series. As shown in FIG. 7, the second objective lens 46 and the first objective lens 35 face each other while approaching so as to position the holding unit 1 therebetween.

  As shown in FIG. 7, the holding unit 1 holding the biomaterial 12 is detachably installed on the installation unit 2 and can be moved by the holding unit moving unit 5B and the shape detecting unit 3 and the light emission state. It is supported with the detection means 4. The holding part moving means 5B can move the holding part 1 and the installation part 2 in the X-axis direction. Further, although not shown, the holding unit moving means 5B can move the holding unit 1 in the Y-axis direction and the Z-axis direction.

  When capturing a visible image of the biological material 12 held in the holding unit 1, the excitation light source 42 is turned off to stop the projection of the excitation light 49, and the white illumination light 36 is applied to the biological material 12 by the illumination unit 31. Hit it. In this case, as can be understood from FIG. 7, the white illumination light 36 strikes the biological material 12 from the back surface 1r side of the holding unit 1 holding the biological material 12, that is, from below the holding unit 1 holding the biological material 12. . As a result, the illuminance near the biomaterial 12 becomes brighter, and an atmosphere suitable for imaging can be obtained. In this way, in the state where the illuminance near the biomaterial 12 is brightened, a visible image of the biomaterial 12 is captured by the first imaging unit 32.

  Further, when a fluorescent image of the biomaterial 12 is captured, the excitation light source 42 is turned on and the excitation light 49 is projected in the state where the illumination unit 31 is turned off and the projection of the white illumination light 36 is stopped, and the beam splitter 47 is projected. And is applied to the biomaterial 12 of the holding unit 1. That is, the excitation light 49 is applied toward the biomaterial 12 on the holding unit 1 from the surface 1s side of the holding unit 1 holding the biomaterial 12. Thus, when the excitation light 49 strikes the biological material 12, the biological material 12 emits fluorescence. In this manner, the fluorescent image of the biomaterial 12 is captured by the second imaging unit 43 in a state where the biomaterial 12 is caused to emit fluorescence. As described above, since the excitation light 49 is irradiated from the surface 1 s side of the holding unit 1 holding the biomaterial 12, the excitation light 49 does not need to pass through the transparent holding unit 1. The attenuation of the energy of the excitation light 49 due to the transmission through the part 1 can be suppressed, which is advantageous for the fluorescence emission of the biomaterial 12.

  That is, according to the present embodiment, when a visible image of the biological material 12 of the holding unit 1 is captured, the biological material 12 is irradiated with the excitation light 49 while the operation of irradiating the biological material 12 with the white illumination light 36 is performed. Do not perform the operation. Further, when capturing a fluorescent image of the biological material 12 of the holding unit 1, the operation of irradiating the biological material 12 with the excitation light 49 is performed, but the operation of irradiating the biological material 12 with the white illumination light 36 is not performed.

  According to the present embodiment, as shown in FIG. 7, the shape detecting means 3 and the light emission state detecting means 4 are basically arranged along the same axis. For this reason, it is not necessary to move the holding part 1 holding the biomaterial 12 for a long distance in the X-axis direction and the Y-axis direction, and the moving distance of the holding part 1 can be shortened or eliminated. For this reason, the imaging of the visible image by the first imaging unit 32 of the shape detection unit 3 and the imaging of the fluorescent image by the second imaging unit 43 of the light emission state detection unit 4 can be performed in a short time, and the processing speed This is advantageous for suppressing deterioration of the biomaterial 12. Furthermore, since the shape detection means 3 and the light emission state detection means 4 are arranged in parallel in the Z-axis direction, it is advantageous for miniaturization in the Y-axis direction and the X-axis direction.

  According to the present embodiment, as shown in FIG. 7, the shape detection unit 3 is positioned below the holding unit 1, and the light emission state detection unit 4 is positioned above the holding unit 1 in the Z-axis direction. Although arranged in parallel, the present invention is not limited to this, and the shape detecting means 3 is arranged in parallel in the Z-axis direction so that the shape detecting means 3 is located above the holding part 1 and the light emission state detecting means 4 is located below the holding part 1. May be. Further, according to the present embodiment, as shown in FIG. 7, the shape detection unit 3 and the light emission state detection unit 4 are disposed to face each other in the Z-axis direction (height direction). The shape detection unit 3 and the light emission state detection unit 4 may be arranged to face each other in the Y axis direction, or may be arranged to face each other in the X axis direction.

(Embodiment 3)
8 and 9 show the third embodiment. The present embodiment has basically the same configuration as that of the first embodiment, and basically has the same function and effect. Hereinafter, a description will be given centering on portions different from the first embodiment. According to the present embodiment, the imaging unit 83 is shared by the shape detection unit 3 and the light emission state detection unit 4, and is the only imaging unit in the biological information detection apparatus according to the present embodiment.

  This biological information detection apparatus is provided in an extension barrel 80 that extends in one direction and forms a cylindrical shape that functions as an optical path forming member for forming an optical path, and an extension portion 81 of the extension barrel 80 and is held by the holding portion 1. An excitation light source 42 that applies the excitation light 49 to the living body material 12 and an imaging unit 83 that is formed by a CCD camera as an imaging unit that images the biological material 12 to which the excitation light 49 projected from the excitation light source 42 is applied. And a lens system 84 provided in the extension barrel 80. The lens system 84 is formed by the imaging lens 45 and the objective lens 46. The lens system 84 is provided so that its focal length is variable. That is, the distance between the objective lens 46 and the holding unit 1 on the installation unit 2 is variable.

  The wavelength of the excitation light 49 from the excitation light source 42 can be appropriately selected according to the color of fluorescent light emitted from the biological material 12. Between the excitation light source 42 and the biomaterial 12 of the holding unit 1, a filter 48 that functions as a selection unit that selects and transmits light in a specific wavelength range, and a shutter 89 that functions as a light shielding unit that can be opened and closed are provided. It has been.

  In this embodiment, the excitation light source 42 is continuously turned on with the shutter 89 closed, and the excitation light 49 is always projected. When the excitation light 49 is required, the shutter 89 is opened, so that the excitation light 49 of the excitation light source 42 reaches the biological material 12 via the beam splitter 47 to excite the biological material 10, and the biological material 12 emits fluorescence. Like to do. When the excitation light 49 of the excitation light source 42 is unnecessary, the shutter 89 is closed so that the excitation light 49 of the excitation light source 42 does not reach the biological material 12.

  If the excitation light source 42 is frequently turned on and off in a short time, it is disadvantageous in terms of ensuring the durability of the excitation light source 42. Therefore, according to the present embodiment, the excitation light source 42 is kept on as described above, the shutter 89 is closed when the excitation light 49 is unnecessary, and the shutter 89 is opened when the excitation light 49 is required. I have decided. In this way, the excitation light source 42 does not have to be frequently turned on and off in a short time, which is advantageous for ensuring the durability of the excitation light source 42 over a long period of time.

  According to this embodiment, when the illumination unit 31 of the shape detection unit 3 is activated and a visible image is captured in a state where the white illumination light 36 is irradiated on the biological material 12, the shutter 89 is closed, and as a result, the light emission is performed. The excitation light 49 projected from the excitation light source 42 of the situation detection means 4 is prevented from hitting the biological material 12. For this reason, the excitation light 49 is not irradiated to the biomaterial 12 during imaging of a visible image, and imaging of a visible image can be performed satisfactorily.

  The usage pattern will be described with reference to the flowchart shown in FIG. According to the present embodiment, the biological material 12 in which the fluorescent compound is introduced and supported by the injection operation is held in the holding unit 1, and the holding unit 1 is installed in the installation unit 2. Then, after the initial setting (step S10), the control unit 101 appropriately drives the holding unit moving unit 5 to set the holding unit 1 at an imageable position (step S12). Further, the excitation light source 42 is turned on, the illumination unit 31 for the white illumination light 36 is turned off, the imaging unit 83 is turned off, and the shutter 89 is closed. This is a standby state.

  Next, a fluorescent image capturing step (step S14) is performed. In this case, the shutter 89 is opened, the excitation light 49 of the excitation light source 42 is projected toward the filter 48, and is excited to the biological material 12 of the holding unit 1 through the filter 48, the opened shutter 89, and the beam splitter 47. Light is applied to excite the biomaterial 12 carrying the fluorescent compound, causing the biomaterial 12 to emit fluorescence. In this manner, with the fluorescent light emitted from the biomaterial 12, the imaging unit 83 is turned on to capture a fluorescent image of the biomaterial 12. When capturing a fluorescent image, the illumination unit 31 is off.

  Thereafter, the shutter 89 is closed to perform the visible image capturing step (step S <b> 16), so that the excitation light 49 projected from the excitation light source 42 is not projected onto the biological material 12. Furthermore, the illumination unit 31 is turned on, the white illumination light 36 of the illumination unit 31 is applied to the biomaterial 12 of the holding unit 1, and a visible image of the biomaterial 12 in a state where the white illumination light 36 is applied in this way is imaged. 83. Thereafter, the next holding unit 1 is moved, and the next biomaterial 12 is brought close to the objective lens 86 (step S18). After executing the fluorescence image capturing process in this way, the visible image capturing process is performed.

  According to the present embodiment, since the imaging unit 83 is commonly used for imaging both the visible image and the fluorescence image, as can be understood from FIG. 8, the imaging of the visible image and the fluorescence image of the same biomaterial 12 are performed. Imaging can be performed by the common imaging unit 83 without moving the biomaterial 12. For this reason, it is not necessary to move the holding | maintenance part 1 holding the biomaterial 12 for a long distance. For this reason, imaging of a visible image and imaging of a fluorescence image can be performed quickly in a short time, and the processing speed can be increased. Furthermore, since the imaging unit 83 captures the visible image and the fluorescent image in common, the number of the imaging units 83 can be reduced, which is advantageous in downsizing and cost reduction.

(Test example)
FIG.10 and FIG.11 shows the result of the test example imaged about the egg of a small fish (zebrafish). In this test, a visible image and a fluorescence image were taken for an egg that had passed 6 hours from the reference time, a state that had passed 12 hours, and a state that had passed 24 hours. FIG. 10 schematically shows a visible image in an egg growth process. FIG. 11 schematically shows a fluorescence image in the course of egg growth. The depth of focus of the visible image and the fluorescent image is the same. As shown in FIG. 10, according to the visible image, the egg initially shows a circular outline, but grows to become juvenile as time elapses over 6 hours, 12 hours, and 24 hours. You can see clearly.

  On the other hand, as shown in FIG. 11, according to the fluorescence image, the fluorescent light emitting portion of the biomaterial 12 is changed, but unlike the visible image, the outline is clear in the egg or the growing fry. is not. For this reason, it is difficult to specify which part the fluorescent light emission part of an egg or fry corresponds to by using only the fluorescent image. However, if the visible image and the fluorescent image are overlaid, or the visible image and the fluorescent image are aligned and compared, it is easy to specify the position of the fluorescent light emitting portion assumed to be an egg or a fry of the growing process.

  As described above, transparent fish eggs are used as biomaterials, and the influence of environmental chemicals on eggs and fry can be observed. In other words, a chemical substance is introduced into a transparent fish egg as a fluorescent protein promoter, and the whole image of the egg is visualized with a visible image as to how the biological substance in the egg is affected by the introduced chemical substance. At the same time, the changes in the fluorescence characteristics emitted by the fluorescent protein due to the introduced chemical substance are converted into information by the fluorescence image, and the two image information of the visible image and the fluorescence image are overlaid or compared side by side, so that the fish egg It is possible to measure the change over time of chemical substances in the process of growing into fry.

In addition, the present invention is not limited to the embodiment described above and shown in the drawings, and can be implemented with appropriate modifications without departing from the scope of the invention. The following technical idea can also be grasped from the above description.
[Additional Item 1] A shape detection step of detecting information related to the shape of the biomaterial held in the holding unit in a state in which the holding unit holding the biomaterial is installed in the installation unit; And a light emission state detection step of detecting information on the light emission state inside the living biological material.
[Additional Item 2] In Additional Item 1, the shape detecting step detects information related to the shape of the biomaterial by capturing a visible image of the biomaterial held in the holding unit. Information detection method.
[Additional Item 3] In Additional Item 1 or 2, after performing the light emission state detection step of imaging the biomaterial that emits light in a state where the biomaterial is irradiated with excitation light and fluorescent light is emitted inside the biomaterial, A biological information detection method, comprising: performing a shape detection step of imaging a shape (including an outline) of a biomaterial with an imaging unit. This is advantageous in suppressing deterioration of the fluorescence emission of the biomaterial.

  INDUSTRIAL APPLICABILITY The present invention can be used for a biological information detection apparatus that detects information related to biological materials such as biological tissue, cells, eggs, DNA, antibodies, and the like.

It is a block diagram which shows typically the concept of the state which is imaging the visible image with the shape detection means in the biometric information detection apparatus which concerns on Embodiment 1. FIG. It is a block diagram which shows typically the concept of the state which has imaged the fluorescence image with the light emission condition detection means in the biological information detection apparatus which concerns on Embodiment 1. FIG. It is a top view which shows typically the principal part of a holding | maintenance part. It is sectional drawing which shows the principal part of a holding | maintenance part typically. It is a block diagram which shows a visible image. It is a block diagram which shows a fluorescence image. It is a block diagram which shows typically the concept of the biometric information detection apparatus which concerns on Embodiment 2. FIG. It is a block diagram which shows typically the concept of the biometric information detection apparatus which concerns on Embodiment 3. FIG. 10 is a flowchart executed by a control unit according to the third embodiment. It is a figure which shows typically the result of having imaged the visible image about the egg of fish (zebrafish). It is a figure which shows typically the result of having imaged the fluorescence image about the egg of fish (zebrafish).

Explanation of symbols

  In the figure, 1 is a holding unit, 12 is a biomaterial, 2 is an installation unit, 3 is a shape detection means, 31 is an illumination unit, 32 is a first imaging unit, 33 is a lens system, 34 is a first imaging lens, 35 Is the first objective lens, 36 is the white illumination light, 4 is the light emission state detection means, 42 is the excitation light source, 43 is the second imaging unit, 44 is the second lens system, 45 is the second imaging lens, and 46 is the first Two objective lenses, 49 is excitation light, 5 is holding unit moving means, 50 is an X-axis stage, 56 is a Y-axis stage, and 70 is a Z-axis stage.

Claims (10)

An installation part capable of installing a holding part for holding a biomaterial;
Shape detecting means for detecting information related to the shape of the biomaterial held in the holding unit;
A biological information detection apparatus comprising: a light emission state detection unit that detects information related to a light emission state of the biological material held in the holding unit.   The biological information detection apparatus according to claim 1, wherein the shape detection unit detects information related to a shape of the biomaterial by capturing a visible image of the biomaterial held in the holding unit.   3. The imaging device according to claim 1, wherein the shape detection unit images an illumination unit that applies visible light to the biomaterial held by the holding unit, and an image of the biomaterial to which the visible light of the illumination unit is applied. And a biological information detecting device.   4. The imaging unit according to claim 3, wherein at least one of the shape detection unit and the light emission state detection unit includes an imaging unit capable of forming an image of a biomaterial held by the holding unit, the imaging unit, and the holding unit. And a lens system arranged between the two.   5. The light emission state detection unit according to claim 1, wherein the light emission state detection unit applies an excitation light to the biological material held in the holding unit to emit light in the biological material, and emits light. A biological information detection apparatus comprising: an imaging unit that images a living biological material. 3. The shape detection unit according to claim 1, wherein the shape detection unit is configured to capture an illumination unit that applies visible light to the biomaterial held by the holding unit, and a biomaterial to which the visible light of the illumination unit is applied. And 1 imaging unit,
The light emission state detection means includes an excitation light source that emits light inside the biological material by applying excitation light to the biological material held in the holding unit, and a second imaging unit that images the emitted biological material. And
After the biological material held in the holding unit is irradiated with excitation light and is emitted inside the biological material, the emitted biological material is imaged by the second imaging unit of the light emission state detecting means, A biological information detection apparatus comprising: a control unit configured to perform an operation so as to image a biological material with a first imaging unit of a shape detection unit.   In any one of Claims 1-6, the said shape detection means and the said light emission condition detection means are arrange | positioned at intervals, Furthermore, the said shape detection means and the said light emission condition detection means, A biological information detection apparatus comprising a holding unit moving unit that moves the holding unit relative to the shape detecting unit and the light emission state detecting unit.   In any one of Claims 1-7, the said shape detection means and the said light emission condition detection means are such that the said holding | maintenance part is located between the said shape detection means and the said light emission condition detection means. A biological information detection device characterized by being arranged to face each other.   The biological information detection apparatus according to claim 1, wherein the biological material is at least one of biological tissue, cells, eggs, DNA, and antibodies of a living organism.   10. The biomaterial according to any one of claims 1 to 9, wherein the biomaterial supports or is capable of supporting a fluorescent compound, and the fluorescent compound is a fluorescent protein, Texas red, fluorescein isothiocyanate (FITC). ), At least one of fluorescein, rhodamine, coumarin, and cascade blue.

Images