JP2014006196A - Fluorescence detecting apparatus - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain stable operation and high-quality fluorescent images even when an excitation optical system and a detection optical system are mounted on a single scanning module.SOLUTION: In a fluorescence detecting apparatus, heat from a light source driver circuit 38 is transmitted to a substrate holder 34 via a projection 39. Since the rear face of the substrate holder 34 is away from a resin frame 33, heat of the substrate holder 34 is discharged into space. In this way, the heat of the light source driver circuit 38 is quickly discharged via the substrate holder 34 to enhance the heat radiating performance of the light source driver circuit 38. As a result, the operation of the light source driver circuit 38 is stabilized to enhance the quality of the fluorescent image that is obtained. Furthermore, since the substrate holder 34 is away from the resin frame 33, heat of the light source driver circuit 38 is not transmitted toward the resin frame 33 side. Hence, the resin frame 33 and the detection optical system fixed to and supported by the resin frame 33 are thermally deformed and deterioration in the fluorescent image quality can be restrained.

Description

  The present invention relates to a fluorescence detection apparatus.

  Conventionally, a fluorescence detection system using a fluorescent dye as a labeling substance has been widely used in the fields of biochemistry and molecular biology. By using this fluorescence detection system, it is possible to evaluate gene sequences, gene mutation / polymorphism analysis, protein separation and identification, and the like, which are used for development of drugs and the like.

  As an evaluation method using a fluorescent label as described above, a method is often used in which biological compounds such as proteins are distributed in a gel by electrophoresis and the distribution of the biological compounds is obtained by fluorescence detection. ing. In the electrophoresis, an electrode is placed in a solution such as a buffer solution, and an electric field gradient is generated in the solution by flowing a direct current. At this time, when there is a charged protein, DNA (Deoxyribonucleic acid: deoxyribonucleic acid) or RNA (ribonucleic acid: ribonucleic acid) in the solution, the positively charged molecule is the cathode, the negatively charged molecule is The biomolecules can be separated by being attracted to the anode.

  Two-dimensional electrophoresis, which is one of the evaluation methods using electrophoresis, is an evaluation method that distributes biomolecules two-dimensionally in a gel by combining two types of electrophoresis methods. Proteomic analysis It is considered the most effective way to do it.

  Examples of the combination of the electrophoresis include, for example, “isoelectric focusing using the difference in isoelectric point of each protein” as the first dimension and “SDS that performs separation based on the molecular weight of the protein” as the second dimension. -PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) "is mainly used. A fluorescent dye is applied to the protein as the biomolecule thus separated before or after electrophoresis.

  Furthermore, the gel support on which the biomolecules (proteins) prepared as described above are two-dimensionally distributed is irradiated with excitation light, and the generated fluorescence intensity is obtained, and the fluorescence distribution (protein Distribution) Image readers that display images are widely used in the fields of biochemistry and molecular biology.

  As a method for maintaining the two-dimensional distribution of the biomolecules, not only the gel is retained in the gel, but also the protein is separated from the gel and then the membrane is separated from the gel using electrophoresis or capillary action. There is also a method of transferring to the surface. In that case, as in the case of image reading using the gel support, the fluorescence distribution on the transfer support, which is the membrane, can be imaged by an image reading device.

  As an image reading device that reads a biomolecule distribution image from a gel support or transfer support in which biomolecules are two-dimensionally distributed as described above, an image disclosed in Japanese Patent Laid-Open No. 10-3134 (Patent Document 1) There is a reader.

  In the conventional image reading apparatus, a mirror having a hole in the center is mounted on an optical head moved in the main scanning direction, and a transfer support on which electrophoresis of denatured DNA labeled with a fluorescent substance is recorded is recorded. On the other hand, a laser beam (excitation light) having a wavelength corresponding to the wavelength of the fluorescent material from the light source is irradiated through the hole of the mirror. Then, the fluorescence emitted when the fluorescent dye in the transfer support is excited is reflected around the hole of the mirror, and is detected by being photoelectrically converted by a multiplier. Thus, image data for one line is stored in the line buffer. Hereinafter, by repeating the above operation while moving the optical head in the sub-scanning direction orthogonal to the main scanning direction, a two-dimensional visible image (fluorescent image) is obtained by the image processing apparatus.

  As described above, in the conventional image reading apparatus, since excitation light is irradiated to the transfer support without using a dichroic mirror, strong excitation energy is higher than that of a method in which excitation light is irradiated through a dichroic mirror. The S / N of a signal (image information) that can be applied to the transfer support and photoelectrically detected can be improved.

  However, when detecting weak fluorescence, further improvement in S / N is required. Therefore, as an optical head type image reading apparatus in which the S / N of the detection signal is further improved as compared with the conventional image reading apparatus, the image information reading disclosed in Japanese Patent Laid-Open No. 2000-162126 (Patent Document 2). There is a device.

  In this image information reading device, a mirror having a hole formed in the center is mounted on an optical head moved in the main scanning direction, and a transfer support on which a biological substance labeled with a fluorescent dye is distributed, Laser light having a wavelength for exciting the fluorescent dye from the laser light source is irradiated upward through the hole of the mirror. Then, the fluorescent dye in the transfer support is excited and the fluorescence emitted downward reaches the mirror. On the other hand, the fluorescence emitted upward from the transfer support is reflected by the inner surface of the concave mirror, travels downward, passes through the transfer support, and reaches the mirror in the optical head. Thus, the two fluorescent lights that have reached the mirror are reflected around the hole of the mirror and are detected by being photoelectrically converted by the multiplier. Thus, image data for one line is stored in the line buffer. Hereinafter, by repeating the above operation while moving the optical head in the sub-scanning direction orthogonal to the main scanning direction, a two-dimensional visible image (fluorescent image) is obtained by the image processing apparatus.

  In this way, the amount of fluorescent light detected by the multiplier can be increased, and the S / N of the photoelectrically detected signal (image information) can be improved.

  However, each of the conventional image information reading devices has the following problems.

  That is, the optical path of the laser light from the laser light source to the transfer support and the optical path of the fluorescence from the transfer support to the photomultiplier are long, and each optical path is extended when the entire image information reader is thermally expanded. A large percentage. Therefore, there is a problem that the optical characteristics deteriorate due to the positional relationship of optical members such as lenses and mirrors deviating from the design value.

  Therefore, it is conceivable to shorten the length of each optical path by mounting an excitation optical system including the laser light source and a detection optical system for detecting fluorescence from the transfer support in a scanning module that performs two-dimensional scanning.

  However, in that case, it is necessary to mount the control circuit for the excitation optical system and the detection optical system in the scanning module, and in particular, the light source driver circuit itself due to the heat generated by the light source driver circuit that drives the light source. There is a problem that the operation of becomes unstable. Furthermore, there is a problem that the optical system composed of the excitation optical system and the detection optical system is thermally expanded by heat from the light source driver circuit, and the optical characteristics of the optical equipment constituting the optical system are deteriorated.

Japanese Patent Laid-Open No. 10-3134 JP 2000-162126 A

  Therefore, an object of the present invention is to provide a fluorescence detection apparatus that can obtain a stable operation and a high-quality fluorescence image even when the excitation optical system and the detection optical system are mounted on one scanning module.

In order to solve the above problems, the fluorescence detection apparatus of the present invention is:
A light source that emits excitation light that excites a fluorescent material;
A fluorescence detector that detects fluorescence emitted from the detection object based on the irradiation of the excitation light;
A condensing unit that condenses the fluorescence from the detection object on the fluorescence detection unit;
An optical member support that supports each optical member included in the light source, the fluorescence detection unit, and the light collection unit;
A light source driving board on which a light source driver circuit for driving the light source is mounted;
A plate-like substrate holder that supports the light source drive substrate,
The light source driving board is attached to the substrate holder with the mounting surface of the light source driver circuit facing one surface of the substrate holder and the light source driver circuit in contact with the one surface of the substrate holder,
The substrate holder is attached to the optical member support,
The other surface of the substrate holder opposite to the one surface is separated from a portion of the optical member support that supports the optical members of the light condensing unit and the fluorescence detecting unit.

  According to the above configuration, the heat from the light source driver circuit is transmitted to the substrate holder that is in contact with the light source driver circuit, and is released to the space from the other surface of the substrate holder. Thus, the heat of the light source driver circuit is quickly released through the substrate holder, and the heat dissipation of the light source driver circuit is enhanced. Therefore, the operation of the light source driver circuit is stabilized, and the quality of the obtained fluorescent image is improved.

  Further, the other surface of the substrate holder is separated from a portion of the optical member support that supports the optical members of the light collecting unit and the fluorescence detection unit. Therefore, the heat released from the other surface of the substrate holder to the space is not transmitted to the optical members of the condensing unit and the fluorescence detecting unit via the optical member support, It can prevent that a member expands thermally and the optical characteristic of each said optical member falls.

  That is, even when the excitation optical system and the fluorescence detection optical system are supported by one optical member support, stable operation of the light source driver circuit and a high-quality fluorescent image can be obtained.

Moreover, in the fluorescence detection device of one embodiment,
The substrate holder has a plurality of attachment members,
The light source drive substrate is attached to the substrate holder via the attachment member.

  According to this embodiment, the light source driving substrate is attached to the substrate holder at a plurality of locations via the attachment member, whereby the strength against deformation of the light source driving substrate is further enhanced by the substrate holder. Can do.

Moreover, in the fluorescence detection device of one embodiment,
On the one surface in contact with the light source driver circuit in the substrate holder, a thermally conductive gel body is provided,
The substrate holder is in contact with the light source driver circuit through the thermally conductive gel body.

  According to this embodiment, since the thermally conductive gel body is interposed between the substrate holder and the light source driver circuit, fluctuations in the distance between the light source driver circuit and the substrate holder are It can be absorbed by the elasticity of the thermally conductive gel body. Therefore, it is possible to prevent poor contact of the substrate holder with the light source driver circuit when the distance is widened, and to improve thermal conductivity. Alternatively, the light source drive board can be prevented from being damaged due to an overload on the light source drive board when the distance is narrowed.

Moreover, in the fluorescence detection device of one embodiment,
An elastic member is provided on the one surface that contacts the light source driver circuit in the substrate holder,
The substrate holder is in contact with the light source driver circuit via the elastic member.

  According to this embodiment, since the elastic member is interposed between the substrate holder and the light source driver circuit, fluctuations in the distance between the light source driver circuit and the substrate holder are reduced. Can be absorbed by elasticity. Therefore, it is possible to prevent poor contact of the substrate holder with the light source driver circuit when the distance is widened, and to improve thermal conductivity. Alternatively, the light source drive board can be prevented from being damaged due to an overload on the light source drive board when the distance is narrowed.

Moreover, in the fluorescence detection device of one embodiment,
The condensing unit and the fluorescence detection unit are arranged in a vertical direction,
The optical member support includes a vertical optical member support that supports each optical member of the light collecting unit and the fluorescence detection unit, and the substrate holder hangs down from an attachment position on the optical member support, And it is attached in parallel to the vertical optical member support.

  According to this embodiment, by hanging the substrate holder from the mounting position on the optical member support, the light source drive substrate attached to the substrate holder is suspended downward, and the light source drive substrate is attached. Stability can be improved. Furthermore, since the condensing unit and the fluorescence detection unit have a long structure below, a structure in which the substrate holder and the light source drive substrate are suspended downward in parallel to the long vertical optical member support unit. By doing so, it is possible to make the fluorescent detection device compact in the horizontal direction.

Moreover, in the fluorescence detection device of one embodiment,
A scanning device that scans the optical member support to which the substrate holder is attached in two dimensions relative to the detection target is provided.

  According to this embodiment, the fluorescence information in the detection object is scanned two-dimensionally so that heat from the light source driver circuit is not transmitted to the optical members of the light collecting unit and the fluorescence detection unit. It is possible to provide a fluorescence detection apparatus that can obtain a high-quality fluorescence image.

  As is clear from the above, the fluorescence detection device of the present invention transfers heat from the light source driver circuit to the substrate holder in contact with the light source driver circuit, and from the other surface of the substrate holder to the space. Since it emits, the heat dissipation of the light source driver circuit can be improved, the operation of the light source driver circuit can be stabilized, and the quality of the obtained fluorescent image can be improved.

  Furthermore, since the other surface of the substrate holder is separated from a portion of the optical member support that supports the optical member of the light collecting unit and the fluorescence detecting unit, the other surface of the substrate holder is spaced from the other surface. It is possible to prevent the released heat from being transmitted to each optical member included in the fluorescence detection unit and the light collection unit via the optical member support. Therefore, it is possible to prevent the optical characteristics from deteriorating due to the thermal expansion of each optical member.

  That is, according to the present invention, even when the excitation optical system and the fluorescence detection optical system are supported by one optical member support to increase the sensitivity, stable operation of the light source driver circuit and high-quality fluorescent image can be obtained. Can be obtained.

  Further, the substrate holder has a plate-like shape facing the mounting surface of the light source driver circuit in the light source drive substrate, and the light source drive substrate is attached to the plate-like substrate holder. The strength against deformation of the light source driving substrate can be enhanced by the substrate holder.

  Further, since the substrate holder has both a function as an attachment member for the light source driving substrate and a function as a heat dissipation member for the light source driver circuit, the number of members can be reduced.

  Further, the substrate holder has a parallel plate-like shape facing the light source driving substrate and the light source driver circuit with a small gap of about the height. Therefore, a set of the light source driving substrate and the substrate holder as a substrate mounting member can be formed into a flat and compact shape as a whole. Furthermore, the area of the heat radiating surface of the substrate holder can be increased while ensuring the strength against deformation of the light source driving substrate.

It is an external view in the fluorescence detection apparatus of this invention. It is an external view of the scanning stage installed in the lower part of the sample stand in FIG. It is sectional drawing of the scanning module mounted on the 2nd stage in FIG. It is a figure which shows the attachment structure to the scanning module in the mounting substrate of a light source driver circuit. It is a figure which shows the attachment procedure of the said mounting board | substrate with respect to the said scanning module. It is a figure which shows the attachment structure to the scanning module in the mounting substrate of the light source driver circuit different from FIG. It is a figure which shows the contact structure with the light source driver circuit of a board | substrate holder.

  Hereinafter, the present invention will be described in detail with reference to the illustrated embodiments.

-1st Embodiment FIG. 1: is an external view in the fluorescence detection apparatus of 1st Embodiment. The fluorescence detection apparatus 1 is roughly configured by a main body 2 that forms a casing and a lid 3 that covers an upper surface of the main body 2. A sample table 4 made of glass is provided on the upper surface of the main body 2, and a transfer support such as a gel support or a membrane on which a biological material labeled with a fluorescent material is distributed (both on the sample stand 4). (Not shown) is set as a sample (measuring object).

  An optical system is arranged below the sample table 4, and the sample set on the sample table 4 is irradiated with excitation light from below through the sample table 4 by the excitation optical system. Fluorescence from the sample passing through 4 is detected by a detection optical system. The detection optical system is connected to an external terminal such as a PC (Personal computer) 5 and controls measurement conditions from the PC 5. Further, the PC 5 creates a fluorescence image of the sample based on the detection data, and displays the created fluorescence image or the like on the built-in display screen.

  FIG. 2 shows an external view of the scanning stage 6 installed at the lower part of the sample table 4. The scanning stage 6 includes a first stage 7 serving as a reference and a second stage 8 placed on the first stage 7. A scanning module 9 is placed on the second stage 8. The excitation optical system including the excitation light source and the detection optical system for detecting the fluorescence are stored in a scanning module 9.

  As described below, the excitation optical system and the detection optical system are integrally mounted on the scanning module 9 that performs two-dimensional scanning as described below, so that the optical path from the light source to the sample and the detector for detecting fluorescence from the sample are detected. By shortening the optical path, the weak fluorescence can be detected without loss, and a highly sensitive fluorescent image can be obtained.

  The first stage 7 constituting the scanning stage 6 is provided with two guide rails 10a and 10b extending in the first scanning direction and facing each other at a constant interval. The second stage 8 is guided by the guide rail 10a of the first stage 7 and reciprocates in the first scanning direction. The second stage 8 is guided by the guide rail 10b and reciprocates in the first scanning direction. And a second guide member 12 that moves.

  Between the first guide member 11 and the second guide member 12 constituting the second stage 8, the second stage 8 extends in the second scanning direction orthogonal to the first scanning direction and faces each other at a constant interval. Two guide shafts 13a and 13b are provided. Further, the scanning module 9 is provided with holes through which the guide shafts 13a and 13b are inserted. The scanning module 9 is guided by the guide shafts 13a and 13b and reciprocates in the second scanning direction.

  In the scanning method using the scanning stage 6 having the above-described configuration, first, the first guide member 11 and the second guide member 12 of the second stage 8 are guided by the guide rails 10a and 10b and moved in the first scanning direction. Thus, the positioning of the second stage 8 with respect to the first stage 7 is performed. After that, the scanning module 9 is guided by the guide shafts 13a and 13b and moved in the second scanning direction, and the scanning module 9 is positioned with respect to the second stage 8. Thereafter, the above operation is repeated to scan the sample 16 two-dimensionally.

  Although not described in detail, the first and second guide members 11 and 12 of the second stage 8 are provided on the lower side of the scanning stage 6 below the sample table 4 of the main body 2 constituting the casing. In the scanning direction, scanning devices such as a motor, a timing belt, a ball screw, a gear, a control board, a power source and wiring for moving the scanning module 9 in the second scanning direction are installed.

  FIG. 3 is a longitudinal sectional view showing a schematic configuration of the scanning module 9 placed on the second stage 8.

  In FIG. 3, an objective lens 17 for concentrating the fluorescence from the sample 16 set on the sample table 4 is disposed on the scanning module 9 in the vicinity of the sample table (glass) 4. Yes. Further, at a position where the optical axis of the objective lens 17 and the optical axis of the light source 18 for excitation light are orthogonal, excitation light such as laser light emitted from the light source 18 and condensed by the first lens 19 is applied to the objective lens 17. The prism 20 that reflects the light so as to be incident on is arranged.

  An excitation optical system including the light source 18, the first lens 19, the prism 20 and the objective lens 17 is fixed and supported on a metal frame 21. Therefore, the heat dissipation of the light source 18 is good, and the excitation optical system has a structure that is not easily thermally deformed. Therefore, the excitation light emitted from the light source 18 can be condensed with respect to one minute point on the sample 16 without shifting. Further, since there is little deviation with respect to one point on the sample 16, the length of the prism 20 in the longitudinal direction (direction perpendicular to the optical axis of the first lens 19) is short, and the width in the direction perpendicular to the longitudinal direction is narrowed. And can be made smaller.

  In FIG. 3, below the prism 20 on the optical axis of the objective lens 17, a second lens for converting fluorescence from the sample 16 collected by the objective lens 17 into parallel light in order from the prism 20 side. 22, a wavelength filter 23 for cutting excitation light, a third lens 24 for condensing fluorescence that has passed through the wavelength filter 23, and a pinhole 25 for cutting stray light of the fluorescence that has passed through the third lens 24 are disposed. . Further, below the pinhole 25 on the optical axis of the objective lens 17, a detector 26 including the detection element that detects fluorescence that has passed through the pinhole 25 is disposed.

  A detection optical system including the second lens 22, the wavelength filter 23, the third lens 24, the pinhole 25, and the detector 26 is fixed and supported on a resin frame 27.

  As described above, in FIG. 3, since the fluorescence diameter is large, the second lens 22 and the third lens 24 having a large aperture are used in the detection optical system. In that case, if the frame for supporting the large-diameter lenses 22 and 24 is made of metal, the weight of the detection optical system increases, making it difficult to scan the scanning module 9 at a high speed and increasing the scanning time.

  On the other hand, if the frame supporting the large-diameter lenses 22 and 24 is made of a resin frame without any ingenuity for weight reduction, the optical axis of the detection optical system is displaced from the design position due to distortion of the frame 27. The desired performance of the detection optical system cannot be obtained.

  Therefore, in the present embodiment, the optical axis of the detection optical system is set in the vertical direction, and the resin frame 27 that supports the detection optical system is attached to the lower surface of the metal frame 21. . In this way, even when the frame supporting the large-diameter lenses 22 and 24 is reduced in weight as the resin frame 27, the deformation of the detection optical system is limited only in the optical axis direction, and the optical axis shift due to its own weight is prevented. It can be made smaller.

  In the scanning module 9 having the above configuration, the excitation light emitted from the light source 18 is converged by the first lens 19, then reflected by the prism 20, passes through the objective lens 17 and the sample stage 4, and passes through the sample 16. It is condensed at one point on the lower surface. In that case, the length of the prism 20 in the longitudinal direction (direction orthogonal to the optical axis of the first lens 19) is short, the width in the direction orthogonal to the longitudinal direction is narrow, and the excitation light from the light source 18 is the objective light. Only the vicinity of the optical axis of the lens 17 (excitation light transmitting portion) passes therethrough.

  The fluorescence is isotropically emitted from the portion of the sample 16 irradiated with the excitation light to the periphery. The component of the emitted fluorescent light that has passed through the sample stage 4 made of glass and entered the objective lens 17 passes through the objective lens 17, the second lens 22, the wavelength filter 23, the third lens 24, and the pinhole 25. Passed through and detected by detector 26. Then, the signal detected by the detector 26 is subjected to processing such as AD conversion by a built-in AD converter or the like, and then sent to the PC 5. In this way, the fluorescence intensity distribution at each measurement point on the sample 16 is recorded in the internal memory or the like.

  Here, as described above, the fluorescence that has passed through the objective lens 17 becomes convergent light and is guided toward the second lens 22. Then, the light is refracted by the second lens 22 so as to be substantially parallel light. The third lens 24 collects the fluorescence. Moreover, the pinhole 25 is arrange | positioned in order to cut a stray light spatially. In addition, the wavelength filter 23 for cutting the excitation light is disposed, for example, in a rotating folder or the like, and can be replaced with a filter 23a having another wavelength according to the wavelength of the excitation light.

  As shown in FIG. 3, the central portion including the optical axis in the objective lens 17 is a convex lens portion 29 having a function of a normal convex lens (light is deflected only by refraction). Of the fluorescence emitted from the sample 16, the fluorescence having a small emission angle passes through the convex lens portion 29 and is condensed toward the detector 26.

  The periphery of the convex lens portion 29 in the objective lens 17 is a truncated cone-shaped cylindrical body 30 that opens downward. Then, of the fluorescence emitted from the sample 16, fluorescence having a large radiation angle that does not enter the convex lens portion 29 enters the cylindrical body 30 from the upper end surface of the cylindrical body 30, and the cylindrical body 30. Are totally reflected on the outer peripheral surface of the light source, deflected toward the optical axis, and emitted from the lower end surface of the cylindrical body 30 toward the detector 26.

  As described above, among the fluorescent light emitted from the sample 16, fluorescent light having a large radiation angle that does not enter the convex lens portion 29 is totally reflected on the outer peripheral surface of the cylindrical body 30, so that the normal convex lens collects the fluorescent light. Light with a large radiation angle that cannot be emitted can be collected. Therefore, the sensitivity of the detector 26 can be increased.

  The metal frame 21 is connected to the scanning device such as a timing belt. Further, two side holes 21a, 21a (only one side surface 21a appears in FIG. 3) facing each other in the metal frame 21 are provided with two guide shaft insertion holes. Two holes are provided in these holes. The guide shafts 13a and 13b are inserted horizontally. Furthermore, the resin frame 27 that supports the detection optical system is attached to the lower surface of the metal frame 21 that supports the excitation optical system so that the optical axis of the objective lens 17 and the optical axis of the detection optical system coincide with each other. And is suspended vertically. By doing so, since the resin frame 27 is light and the center of gravity is on the metal frame 21 side, twisting and vibration of the scanning module 9 can be suppressed when scanning by the scanning device.

  Hereinafter, a structure for mounting the light source driver circuit for driving the light source 18 to the scanning module 9 on the mounting board will be described in detail.

  FIG. 4 is a schematic view showing a state in which the mounting board is attached to the scanning module 9. FIG. 5 is a schematic view showing a procedure for attaching the mounting board to the scanning module 9.

  In FIG. 4, the scanning module 9 is fixed by a light source 18, a first lens 19 and a prism 20 fixed and supported by a metal frame 31, an objective lens 17 fixed and supported by a metal frame 32, and a resin frame 33. The second lens 22, the wavelength filter 23, the third lens 24, and the pinhole 25 that are supported, and the detector 26 that is externally attached to the resin frame 33.

  In this case, as shown in FIG. 3, the light source 18, the first lens 19, the prism 20, and the objective lens 17 are fixed and supported by a single metal frame 21, and the second lens 22, the wavelength filter 23, the third lens 24, and the pin The hole 25 and the detector 26 may be fixed and supported by the resin frame 27, and the difference in the configuration of the scanning module 9 between FIG. 4 and FIG. 3 is not essential.

  An end surface 31 a located on the side opposite to the light source 18 side of the metal frame 31 as an example of the optical member support protrudes from the side surface 33 a of the resin frame 33. One end of a flat substrate holder 34 is attached to the end surface 31 a of the metal frame 31. Thus, the substrate holder 34 is attached in a state where it is suspended from the metal frame 31 with the one end as the upper end.

  At the four corners of the surface of the substrate holder 34 opposite to the surface on the metal frame 31 side, mounting bases 36a and 36b for mounting the substrate 35 of the light source driver circuit (two mounting bases located on the opposite side appear). Not). And as shown in FIG. 5, the said end of the board | substrate holder 34 is attached to the end surface 31a of the metal frame 31 by adhesion | attachment, for example. In this way, the four corners of the substrate 35 are screws 37a and 37b (the two screws located on the opposite side do not appear) on the mounting bases 36a and 36b of the substrate holder 34 attached in a suspended state with respect to the metal frame 31. It is attached.

  A light source driver circuit 38 is mounted substantially at the center of the substrate 35, and a protrusion 39 is provided at a position facing the light source driver circuit 38 in the substrate holder 34. A resin package (not shown) of the light source driver circuit 38 is in contact with the protrusion 39 of the substrate holder 34.

  The substrate holder 34 is made of metal and has the same size as the substrate 35. The substrate holder 34 has a large surface area and high heat dissipation. Further, as described above, the substrate holder 34 is attached in a suspended state with respect to the end surface 31 a of the metal frame 31 protruding from the side surface 33 a of the resin frame 33. Therefore, the rear surface of the substrate holder 34 that is in contact with the light source driver circuit 38 is separated from the side surface 33 a of the resin frame 33.

  In the above configuration, when a control signal is supplied from the control device 40 to the light source driver circuit 38 mounted on the substrate 35, the light source driver circuit 38 supplies the light source 18 via the substrate 35 and the metal frame 31. A drive signal corresponding to the control signal is supplied to control the light output.

  At that time, the heat generated from the light source driver circuit 38 is transmitted to the substrate holder 34 through the protrusion 39 in contact with the light source driver circuit 38. And since the back surface on the opposite side to the protrusion 39 in the substrate holder 34 is separated from the side surface 33a of the resin frame 33, the heat of the substrate holder 34 is released into the space as shown by the arrow.

  Therefore, the heat generated from the light source driver circuit 38 is quickly released through the substrate holder 34, and the heat dissipation of the light source driver circuit 38 is enhanced. As a result, the operation of the light source driver circuit 38 is stabilized, and the light output of the light source 18 is also stabilized, so that the quality of the obtained fluorescent image can be improved.

  Further, since the substrate holder 34 is separated from the side surface 33a of the resin frame 33, the heat of the light source driver circuit 38 is not transmitted to the resin frame 33 side. Therefore, it can be suppressed that the resin frame 33 is thermally expanded and each optical member of the detection optical system is thermally deformed, and the quality of the fluorescent image is deteriorated.

  Further, the substrate holder 34 is in contact with the light source driver circuit 38 through a protrusion 39 protruding from the surface. Therefore, even when a component higher than the height of the light source driver circuit 38 is mounted on the substrate 35, the height of the projection 39 is the sum of the height of the projection 39 and the height of the light source driver circuit 38. The light source driver circuit 38 can be brought into contact with the substrate holder 34 if it is set to be larger than the height of the component.

  If heat dissipation grease, heat dissipation silicon or the like is applied to the contact surface of the protrusion 39 with the light source driver circuit 38, it is possible to fill a minute gap with the light source driver circuit 38 and reduce the thermal resistance.

  The substrate holder 34 may be attached to the metal frame 31 even if the same screw is used together with the substrate 35.

Second Embodiment The second embodiment relates to a fluorescence detection apparatus having a structure for attaching a light source driver circuit to a scanning module 9 on a substrate different from the case of the first embodiment. Here, the external appearance of the present fluorescence detection apparatus, the structure of the scanning stage, and the structure of the scanning module are exactly the same as those in the first embodiment, and thus description thereof is omitted.

  FIG. 6 is a schematic diagram showing a structure for mounting the light source driver circuit to the scanning module 9 on the substrate in the present embodiment.

  In FIG. 6, the configuration of the scanning module 9 is the same as that of the first embodiment, and therefore, the same reference numerals as those in FIG. An end surface 31 a located on the side opposite to the light source 18 side of the metal frame 31 protrudes from the side surface 33 a of the resin frame 33. Then, one end of a flat substrate holder 41 is attached to the end surface 31 a of the metal frame 31 with a screw 42. Thus, the substrate holder 41 is attached in a state where it is suspended from the metal frame 31 with the one end as the upper end.

  At four locations on the surface of the substrate holder 41 on the metal frame 31 side, mounting bases 44a and 44b for mounting the substrate 43 of the light source driver circuit (two mounting bases on the opposite side do not appear) are provided. It has been. The four corners of the substrate 43 are attached to the mounting bases 44a and 44b of the substrate holder 41 with screws 45a and 45b (the two screws located on the opposite side do not appear).

  A light source driver circuit 46 is mounted substantially at the center of the substrate 43. A resin package (not shown) of the light source driver circuit 46 is in direct contact with the substrate holder 41. In that case, as in the first embodiment, a protrusion may be provided on the substrate holder 41 so that the light source driver circuit 46 contacts the substrate holder 41 via the protrusion.

  As in the case of the first embodiment, the substrate holder 41 is made of metal and has a larger area than the substrate 43, has a large surface area, and has high heat dissipation. Further, as described above, the substrate holder 41 is attached in a suspended state to the end surface 31 a of the metal frame 31 that protrudes from the side surface 33 a of the resin frame 33. The back surface of the mounting surface of the light source driver circuit 46 on the substrate 43 is separated from the side surface 33 a of the resin frame 33.

  In the above configuration, when a control signal is supplied from the control device 47 to the light source driver circuit 46 mounted on the substrate 43, the light source driver circuit 46 passes through the substrate 43, the substrate holder 41, and the metal frame 31. A drive signal corresponding to the control signal is supplied to the light source 18 to control the light output.

  At that time, heat generated from the light source driver circuit 46 is transmitted to the substrate holder 41 in contact with the light source driver circuit 46. And as shown by the arrow, it discharge | releases to the space of the outer side (anti-resin frame 33 side) from the substrate holder 41.

  Thus, in the present embodiment, the substrate 43 is located between the substrate holder 41 and the resin frame 33 of the scanning module 9. Therefore, the back surface of the contact surface with the light source driver circuit 46 in the substrate holder 41 faces the outside (on the side of the anti-resin frame 33), and the heat dissipation from the light source driver circuit 46 is as in the first embodiment. This can be made higher than when the back surface of the contact surface with the light source driver circuit in the substrate holder faces the resin frame 33 side (inside).

Third Embodiment The third embodiment relates to a fluorescence detection apparatus having a contact structure with a light source driver circuit of a substrate holder different from those in the first and second embodiments. Here, the external appearance of the present fluorescence detection apparatus, the structure of the scanning stage, the structure of the scanning module, and the structure for attaching the substrate to the scanning module are exactly the same as those in the first embodiment, and the description thereof will be omitted.

  FIG. 7 is a schematic diagram showing a contact structure of the substrate holder with the light source driver circuit in the present embodiment. Since the substrate holder and the substrate of the light source driver circuit are the same as those in the first embodiment, the substrate holder, the light source driver circuit, and the substrate are assigned the same numbers as those in FIG.

  In FIG. 7A, a leaf spring 51 is sandwiched between the light source driver circuit 38 and the substrate holder 34 that are mounted at a substantially central portion of the substrate 35.

  The leaf spring 51 has a shape in which a thermally conductive metal plate having elasticity is cut into a long rectangular shape, and a central portion thereof is bent into a U shape to provide a protruding portion 51a. The plate spring 51 is attached to the substrate holder 34 by attaching flat base portions 51b and 51b on both sides of the protruding portion 51a to the surface of the substrate holder 34 facing the light source driver circuit 38 with screws 52b and 52b.

  In this case, the distance between the outer surface of the protruding portion 51a and the mounting surface of the base portion 51b is the opposite surface between the top surface of the resin package (not shown) of the light source driver circuit 38 and the light source driver circuit 38 of the substrate holder 34. It is set slightly longer than the distance between. Therefore, when the substrate 35 is attached to the mounting bases 36a and 36b of the substrate holder 34 to which the leaf spring 51 is attached by screws 37a and 37b, the protruding portion 51a of the leaf spring 51 is the top surface of the light source driver circuit 38. It will be in close contact with the elastic force.

  Therefore, fluctuations in the distance between the light source driver circuit 38 and the substrate holder 34 due to the height tolerance of the light source driver circuit 38 and the distance tolerance between the substrate holder 34 and the substrate 35 are represented by the leaf spring 51. It can be absorbed by elasticity. As a result, when the distance between the light source driver circuit 38 and the substrate holder 34 is increased, the substrate 35 is poorly contacted with the light source driver circuit 38, or when the distance is reduced, the substrate 35 is overloaded. Can prevent damage.

  Furthermore, since the leaf spring 51 is formed of a heat conductive metal plate, heat from the light source driver circuit 38 can be quickly transmitted to the substrate holder 34.

  In the present embodiment, the elastic member is constituted by the leaf spring 51, but the present invention is not limited to this. For example, a coil spring or a torsion spring can be used. However, it is necessary to have a structure that can quickly transfer the heat of the light source driver circuit 38 to the substrate holder 34.

  FIG. 7B is a schematic diagram showing a contact structure with a light source driver circuit of a substrate holder different from that in FIG.

  In FIG. 7B, a heat conductive gel body 55 is sandwiched between the light source driver circuit 38 and the substrate holder 34 that are mounted at a substantially central portion of the substrate 35.

  The heat conductive gel body 55 is formed by filling a heat conductive gel material such as silicon resin in a box-shaped heat conductive container having elasticity or the like. The thermally conductive gel body 55 is attached at a position facing the light source driver circuit 38 in the substrate holder 34 by adhesion or the like.

  In that case, the thickness of the heat conductive gel body 55 in an unloaded state is between the top surface of the resin package (not shown) of the light source driver circuit 38 and the surface of the substrate holder 34 facing the light source driver circuit 38. It is set slightly thicker than the distance. Therefore, when the substrate 35 is attached to the mounting bases 36a and 36b of the substrate holder 34 to which the thermally conductive gel body 55 is attached with the screws 37a and 37b, the thermally conductive gel body 55 is attached to the light source driver circuit 38. It will be in close contact with the top surface by elastic force.

  Therefore, the variation in the distance between the light source driver circuit 38 and the substrate holder 34 due to the height tolerance of the light source driver circuit 38 and the tolerance of the distance between the substrate holder 34 and the substrate 35 is reduced by the thermal conductivity. It can be absorbed by the elasticity of the gel body 55. As a result, when the distance between the light source driver circuit 38 and the substrate holder 34 is increased, the substrate 35 is poorly contacted with the light source driver circuit 38, or when the distance is reduced, the substrate 35 is overloaded. Can prevent damage.

  Furthermore, since the heat conductive gel body 55 is formed by filling a heat conductive container or the like with a heat conductive gel material, the heat from the light source driver circuit 38 can be quickly transmitted to the substrate holder 34.

  In the present embodiment, the contact structure between the substrate holder and the light source driver circuit has been described as an example applied to the first embodiment. However, the contact structure may be applied to the second embodiment. Needless to say, there is no problem.

  As described above, in each of the above embodiments, the optical axes of the second lens 22, the wavelength filter 23, the third lens 24, and the pinhole 25 as an example of the condensing unit, and the fluorescence detecting unit as an example. A resin frame 33 as an example of the vertical optical member supporting portion that supports the optical member with the optical axis of the detector 26 in a vertical direction is fixed to the light source 18, the first lens 19, and the prism 20. It is attached so as to hang down on the metal frame 31 to be supported. Thus, the metal frame 31, the metal frame 32, and the resin frame 33 form the optical member support.

  And the board | substrates 35 and 43 which are the said light source drive boards in which the light source driver circuits 38 and 46 which drive the said light source 18 were mounted, the mounting surface of the light source driver circuits 38 and 46 are one surface of plate-shaped board | substrate holders 34 and 41. The light source driver circuits 38 and 46 are attached to the substrate holders 34 and 41 in contact with the one surface of the substrate holders 34 and 41.

  Thus, the other surface of the substrate holders 34 and 41 opposite to the one surface is separated from the resin frame 33.

  Therefore, the heat from the light source driver circuits 38, 46 is transferred from the one surface of the substrate holders 34, 41 in contact with the light source driver circuits 38, 46 to the substrate holders 34, 41, and is opposite to the one surface. Released from the other side into the space. In this case, the other surfaces of the substrate holders 34 and 41 are separated from the resin lens 33 that supports the second lens 22, the wavelength filter 23, the third lens 24, the pinhole 25, and the detector 26. Therefore, the heat released from the other surfaces of the substrate holders 34 and 41 to the space is transmitted to the second lens 22, the wavelength filter 23, the third lens 24, the pinhole 25 and the detector 26 via the resin frame 33. The second lens 22, the wavelength filter 23, the third lens 24, the pinhole 25 and the detector 26 are thermally expanded, and the second lens 22, the wavelength filter 23, the third lens 24, the pinhole 25 and the detection are detected. It is possible to prevent the optical characteristics of the device 26 from deteriorating.

  As described above, according to the above embodiments, even when the excitation optical system and the detection optical system are supported by the integrated optical member support, stable operation of the light source driver circuits 38 and 46 and high quality are achieved. A fluorescent image can be obtained.

  Further, the substrate holders 34 and 41 have a plate-like shape corresponding to the mounting surfaces of the light source driver circuits 38 and 46 of the substrates 35 and 43. 43 is attached. Therefore, the strength against deformation of the substrates 35 and 43 can be increased by the substrate holders 34 and 41.

  Further, the substrate holders 34 and 41 as the mounting members also serve as a heat radiating member of the light source driver circuits 38 and 46. Therefore, the number of members can be reduced.

  Further, the substrate holders 34 and 41 have a parallel plate shape facing the substrates 35 and 43 with a narrow space corresponding to the height of the light source driver circuits 38 and 46. Therefore, the set of the board | substrates 35 and 43 and the board | substrate holders 34 and 41 which are board | substrate attachment members has the planar compact shape as a whole. Furthermore, the area of the heat radiating surface, which is the other surface of the substrate holders 34 and 41, can be increased while ensuring the strength against deformation of the substrates 35 and 43.

  In each of the above embodiments, the substrate holders 34 and 41 are provided with mounting bases 36a and 36b; 44a and 44b as examples of the mounting members, and the substrates 35 and 43 are mounted on the mounting base 36a. , 36b; 44a, 44b to the substrate holders 34, 41.

  In this way, by attaching the substrates 35 and 43 to the substrate holders 34 and 41 at a plurality of locations, the strength against deformation of the substrates 35 and 43 can be further enhanced by the substrate holders 34 and 41. The mounting positions of the mounting bases 36a, 36b; 44a, 44b are ideally locations corresponding to the four corners of the substrates 35, 43 in the substrate holders 34, 41. In addition, the light source driver circuits 38 and 46 can be installed at two locations above and below.

  Moreover, in the said 3rd Embodiment, the heat conductive gel body 55 is provided in the said one surface which contacts the light source driver circuit 38 in the said board | substrate holder 34, and the board | substrate holder 34 is interposed via the heat conductive gel body 55. The light source driver circuit 38 is contacted.

  Thus, by interposing the thermally conductive gel body 55 between the substrate 35 and the light source driver circuit 38, the variation in the distance between the light source driver circuit 38 and the substrate holder 34 can be reduced. It can be absorbed by the elasticity of 55. As a result, it is possible to prevent poor contact of the substrate holder 34 with the light source driver circuit 38 and improve thermal conductivity. Alternatively, it is possible to prevent the substrate 35 from being damaged due to overload.

  In the third embodiment, an elastic member is provided on the one surface of the substrate holder 34 that contacts the light source driver circuit 38, and the substrate holders 34 and 41 are connected to the light source driver circuit 38 via the elastic member. I try to make contact.

  Thus, by interposing the elastic member between the substrate 35 and the light source driver circuit 38, the variation in the distance between the light source driver circuit 38 and the substrate holder 34 is absorbed by the elasticity of the elastic member. be able to. As a result, it is possible to prevent poor contact of the substrate holder 34 with the light source driver circuit 38 and improve thermal conductivity. Alternatively, it is possible to prevent the substrate 35 from being damaged due to overload.

  In each of the above embodiments, the optical axes of the second lens 22, the wavelength filter 23, the third lens 24, the pinhole 25 and the detector 26 are set in the vertical direction, and the substrate holders 34 and 41 are connected to the light source 18. The second lens 22, the wavelength filter 23, the third lens 24, the pinhole 25, and the detector 26 are fixedly suspended from the mounting position on the metal frame 31 that fixes and supports the first lens 19 and the prism 20. It is attached in parallel to the resin frame 33 to be supported.

  In this way, by hanging the substrate holders 34 and 41 from the attachment position to the metal frame 21, the substrates 35 and 43 attached to the substrate holders 34 and 41 are structured to hang downward. Stability is improved. Furthermore, since it has a long structure from the second lens 22 to the detector 26, the structure is such that the substrate holders 34, 41 and the substrates 35, 43 hang downward in parallel to the long resin frame 33. As a result, it is possible to contribute to the compactness of the fluorescence detection apparatus in the horizontal direction.

  In each of the above embodiments, the metal frame 31 to which the substrate holders 34 and 41 are attached is scanned relatively two-dimensionally with respect to the detection object by the scanning device. Therefore, the fluorescence information on the detection target can be scanned two-dimensionally so that heat from the light source driver circuits 38 and 46 is not transmitted to the detection optical system, and a high-quality fluorescence image can be obtained. It is possible to provide a fluorescence detection apparatus capable of performing the above.

  In the above embodiments, the control devices 40 and 47 supply control signals to the light source driver circuits 38 and 46 to control the light output of the light source 18. However, the present invention is not limited to this. For example, the detection result from the detector 26 is received to determine the fluorescence detection result, and the main board or the like is controlled according to the determination result to control the two-dimensional display. It is also possible to control the operation speed, the light output of the light source 18, and the like.

  In each of the above embodiments, the substrate holders 34 and 41 are attached to the end surface 31a of the metal frame 31 on the side opposite to the light source 18 side. However, the present invention is not limited to this, and the substrate holders 34 and 41 may be attached to the end face of the metal frame 31 on the light source 18 side in one direction.

1 ... fluorescence detection device,
4 ... Sample stand,
5 ... PC,
6 ... Scanning stage,
7 ... 1st stage,
8 ... Second stage,
9 ... Scanning module,
16 ... sample,
17 ... Objective lens,
18 ... light source,
19 ... first lens,
20 ... Prism,
21, 31, 32 ... metal frame,
22 ... second lens,
23: Wavelength filter,
24 ... Third lens,
25 ... pinhole,
26 ... detector,
27, 33 ... Resin frame,
33a: side surface of resin frame,
34, 41 ... substrate holder,
35, 43 ... substrate,
36a, 36b, 44a, 44b …… Mounting base,
38, 46 ... Light source driver circuit,
39 ... protrusions,
40, 47 ... control device,
51 ... leaf spring,
55 ... Thermally conductive gel body.

Claims (6)

A light source that emits excitation light that excites a fluorescent material;
A fluorescence detector that detects fluorescence emitted from the detection object based on the irradiation of the excitation light;
A condensing unit that condenses the fluorescence from the detection object on the fluorescence detection unit;
An optical member support that supports each optical member included in the light source, the fluorescence detection unit, and the light collection unit;
A light source driving board on which a light source driver circuit for driving the light source is mounted;
A plate-like substrate holder that supports the light source drive substrate,
The light source driving board is attached to the substrate holder with the mounting surface of the light source driver circuit facing one surface of the substrate holder and the light source driver circuit in contact with the one surface of the substrate holder,
The substrate holder is attached to the optical member support,
The other surface of the substrate holder opposite to the one surface is separated from a portion of the optical member support that supports the optical members of the light condensing unit and the fluorescence detecting unit. apparatus. In the fluorescence detection apparatus according to claim 1,
The substrate holder has a plurality of attachment members,
The fluorescence detection apparatus, wherein the light source drive substrate is attached to the substrate holder via the attachment member. In the fluorescence detection device according to claim 1 or 2,
On the one surface in contact with the light source driver circuit in the substrate holder, a thermally conductive gel body is provided,
The fluorescence detection apparatus, wherein the substrate holder is in contact with the light source driver circuit through the thermally conductive gel body. In the fluorescence detection device according to claim 1 or 2,
An elastic member is provided on the one surface that contacts the light source driver circuit in the substrate holder,
The fluorescence detection apparatus, wherein the substrate holder is in contact with the light source driver circuit through the elastic member. In the fluorescence detection device according to any one of claims 1 to 4,
The condensing unit and the fluorescence detection unit are arranged in a vertical direction,
The optical member support includes a vertical optical member support that supports each optical member of the light collecting unit and the fluorescence detection unit, and the substrate holder hangs down from an attachment position on the optical member support, And a fluorescence detecting device mounted in parallel to the vertical optical member support. In the fluorescence detection device according to any one of claims 1 to 5,
A fluorescence detection apparatus comprising: a scanning device configured to scan the optical member support to which the substrate holder is attached relatively two-dimensionally with respect to the detection target.

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