Spectrometer and sample analysis system
The spectrometer system addresses the limitation of fixed wavelength excitation in optical imaging by enabling continuous wavelength change, improving analytical precision and system miniaturization through controlled rotation of scattering units.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Filing Date
- 2023-03-09
- Publication Date
- 2026-03-17
AI Technical Summary
Conventional optical imaging devices cannot continuously change the wavelength of excitation light while irradiating a sample, limiting their analytical capabilities.
A spectrometer system comprising a light source that emits light with multiple wavelengths, an excitation scattering unit, a scanning unit, a fluorescence scattering unit, and a photodetector, which allows for continuous wavelength change of excitation light through controlled rotation of scattering units, enabling continuous fluorescence analysis.
Enables continuous wavelength change of excitation light during irradiation, enhancing analytical precision and accuracy by minimizing noise from surrounding objects, and allowing miniaturization of the system.
Smart Images

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Abstract
Description
Technical Field
[0001] The present disclosure relates to a spectroscopic device and a sample analysis system.
Background Art
[0002] Conventionally, as described in Patent Document 1, an optical imaging device including a plurality of illumination sources, a selectable splitting module, and a splitting element is known. In this optical imaging device, when an illumination source having a first wavelength is used, the first splitting element is selected using the splitting module. Thereby, excitation light of the first wavelength reaches the sample.
Prior Art Documents
Patent Documents
[0003]
Patent Document 1
Summary of the Invention
Problems to be Solved by the Invention
[0004] In the optical imaging device described in Patent Document 1, the wavelength of the excitation light is selected and switched by selecting and switching the illumination source and the splitting element. Therefore, it is not possible to continuously change the wavelength of the excitation light while irradiating the sample with the excitation light.
[0005] An object of the present disclosure is to provide a spectroscopic device and a sample analysis system that can continuously change the wavelength of excitation light while irradiating the sample with the excitation light.
Means for Solving the Problems
[0006] The invention described in claim 1 is a spectrometer comprising: a light source (32) that emits light having multiple wavelengths; an excitation scattering unit (36) that scatters light from the light source; an excitation passing unit (38) that allows some of the light scattered by the excitation scattering unit, which is excitation light, to pass through; a scanning unit (40) that reflects the excitation light that has passed through the excitation passing unit and irradiates a sample (90) coated with a reagent with the reflected light to generate fluorescence, which is light emitted by the sample; a fluorescence scattering unit (48) that scatters the fluorescence; a fluorescence passing unit (50) that allows some of the fluorescence scattered by the fluorescence scattering unit, which is analytical fluorescence, to pass through; a photodetector (52) that receives the analytical fluorescence that has passed through the fluorescence passing unit and outputs a signal corresponding to the intensity of the analytical fluorescence; and an excitation changing unit (S206) that changes the wavelength of the excitation light reflected by the scanning unit by changing the excitation light that passes through the excitation passing unit by driving the excitation scattering unit.
[0007] Furthermore, the invention described in claim 9 includes a light source (32) that emits light having multiple wavelengths, an excitation scattering unit (36) that scatters light from the light source, an excitation passing unit (38) that allows some of the light scattered by the excitation scattering unit, which is excitation light, to pass through, a scanning unit (40) that reflects the excitation light that has passed through the excitation passing unit and irradiates a sample (90) coated with a reagent with the reflected light to generate fluorescence, which is light emitted by the sample, a fluorescence scattering unit (48) that scatters the fluorescence, and the fluorescence scattered by the fluorescence scattering unit The sample analysis system comprises a spectrometer (30) having a fluorescence passage section (50) that allows a portion of the analytical fluorescence to pass through, a photodetector (52) that receives the analytical fluorescence that has passed through the fluorescence passage section and outputs a signal corresponding to the intensity of the analytical fluorescence, and an excitation changing section (S206) that changes the wavelength of the excitation light reflected by the scanning section by changing the excitation light that passes through the excitation passage section by driving an excitation scattering section, and an analysis section (84) that identifies the type of sample based on the intensity of the analytical fluorescence.
[0008] When the excitation scattering unit is activated, the wavelength of the excitation light reflected by the scanning unit is changed. As a result, the wavelength of the excitation light changes continuously while the excitation light is being irradiated.
[0009] The reference numerals in parentheses attached to each component indicate an example of the correspondence between that component and the specific components described in the embodiments described later. [Brief explanation of the drawing]
[0010] [Figure 1] A diagram illustrating the configuration of a sample analysis system using a spectrometer according to one embodiment. [Figure 2] Diagram of the spectrometer's configuration. [Figure 3] Diagram showing the configuration of the excitation scattering section of a spectrometer. [Figure 4] Diagram showing the configuration of the scanning section of a spectrometer. [Figure 5] Diagram showing the configuration of the fluorescence scattering section of a spectrometer. [Figure 6] A flowchart illustrating the processing of the coating control unit in a sample analysis system. [Figure 7] A flowchart illustrating the processing steps of the analysis unit in a sample analysis system. [Figure 8] A diagram showing scanning by the scanning unit. [Figure 9] A diagram showing the relationship between fluorescence wavelength and light intensity for a single sample. [Figure 10] A diagram showing the relationship between fluorescence wavelength and light intensity for two types of samples. [Modes for carrying out the invention]
[0011] The embodiments will be described below with reference to the drawings. In the following embodiments, parts that are the same or equivalent to each other will be denoted by the same reference numeral, and their descriptions will be omitted.
[0012] The spectrometer of this embodiment is used in a sample analysis system that analyzes a sample coated with a reagent. First, this sample analysis system will be described.
[0013] As shown in Figure 1, the sample analysis system 10 identifies the type of sample by analyzing the intensity of fluorescence emitted from the sample coated with the reagent. Specifically, the sample analysis system 10 comprises a coating device 20, a spectrometer 30, and a control device 80.
[0014] The coating device 20 applies a reagent to a sample 90 adhering to the interior of a car or house, walls, furniture, etc., as shown in Figure 2. For example, the coating device 20 has a robot (not shown) and a nozzle mounted on that robot. The robot is controlled by a control device 80, which will be described later. As a result, the nozzle mounted on the robot moves to the location of the area containing the sample 90. Furthermore, the nozzle sprays the reagent. Therefore, the reagent is applied to the area containing the sample 90, and thus applied to the sample 90. The sample 90 is a virus, foreign matter, dirt, etc. The reagent is at least one AIE reagent for detecting viruses, foreign matter, dirt, etc. Furthermore, AIE stands for Aggregation-Induced Emission.
[0015] Returning to Figure 1, the spectrometer 30 irradiates the sample 90, to which the reagent has been applied by the coating device 20, with excitation light, generating fluorescence, which is light emitted by the sample 90. The spectrometer 30 also receives the generated fluorescence and outputs a signal corresponding to the intensity of the received fluorescence to the control device 80, which will be described later. Furthermore, at this time, the spectrometer 30 continuously changes the wavelength of the excitation light. Specifically, as shown in Figure 2, the spectrometer 30 has a light source 32, an excitation aperture 34, an excitation scattering unit 36, an excitation passing unit 38, a scanning unit 40, and an excitation focusing lens 42. The spectrometer 30 also has a fluorescence focusing lens 44, a fluorescence aperture 46, a fluorescence scattering unit 48, a fluorescence passing unit 50, and a photodetector 52.
[0016] The light source 32 emits light having a plurality of wavelengths, and here, it emits white light. For example, the light source 32 is a deuterium discharge tube, a tungsten iodine lamp, a xenon flash lamp, an LED, an LD, or the like. Note that LED is an abbreviation for Light Emitting Diode. Further, LD is an abbreviation for Laser Diode. Also, in FIG. 2, the optical path is schematically shown by an arrow.
[0017] The excitation aperture portion 34 is formed of, for example, a plate-like member. Further, the excitation aperture portion 34 has slits, pinholes, and the like. Also, the light from the light source 32 passes through the slits and pinholes of the excitation aperture portion 34. Thereby, the excitation aperture portion 34 makes the light from the light source 32 into a beam shape by narrowing the light. Further, the excitation aperture portion 34 irradiates the light that has been narrowed onto the excitation scattering portion 36 described later.
[0018] The excitation scattering portion 36 is, for example, a MEMS diffraction grating. Specifically, as shown in FIG. 3, the excitation scattering portion 36 includes an excitation semiconductor substrate 360, an excitation concavo-convex portion 362, an excitation drive portion 364, and the like. Note that MEMS is an abbreviation for Micro Electro Mechanical Systems.
[0019] The excitation semiconductor substrate 360 is, for example, a silicon substrate. Also, the length and width of the excitation semiconductor substrate 360 are, for example, 1 to 10 mm. Furthermore, the thickness of the excitation semiconductor substrate 360 is, for example, 0.2 to 1.0 mm. The excitation uneven portion 362 is formed on the excitation semiconductor substrate 360. Also, the excitation uneven portion 362 scatters the light from the excitation aperture portion 34. Furthermore, the size of the excitation uneven portion 362 is adjusted according to the wavelength band of the excitation light corresponding to the reagent. The excitation drive portion 364 is, for example, an electrostatic drive type actuator using Coulomb attraction by an applied voltage, an electromagnetic drive type actuator using the interaction between a microcoil and a permanent magnet, or the like. Also, when power is supplied to the excitation drive portion 364, the excitation semiconductor substrate 360 is driven. For example, the excitation semiconductor substrate 360 is rotationally driven about an axis extending in one direction. Thereby, the excitation scattering portion 36 is rotationally driven about an axis extending in one direction.
[0020] Returning to FIG. 2, the excitation passage portion 38 is formed of, for example, a plate-like member. Furthermore, the excitation passage portion 38 has a slit, a pinhole, and the like. Also, the slit and the pinhole of the excitation passage portion 38 allow passage of excitation light, which is a part of the light scattered by the excitation scattering portion 36. Furthermore, the excitation passage portion 38 makes the light beam-shaped by narrowing the excitation light. Also, the excitation passage portion 38 irradiates the narrowed excitation light to the scanning portion 40 described later.
[0021] The scanning portion 40 is, for example, a MEMS scanner. Specifically, as shown in FIG. 4, the scanning portion 40 includes a scanning semiconductor substrate 400, a mirror 402, a scanning drive portion 404, and the like.
[0022] The scanning semiconductor substrate 400 is, for example, a silicon substrate. The length and width of the scanning semiconductor substrate 400 are, for example, 1 to 10 mm. Furthermore, the thickness of the scanning semiconductor substrate 400 is, for example, 0.2 to 1.0 mm. The mirror 402 is formed on the scanning semiconductor substrate 400. The excitation light that has passed through the excitation passage section 38 is reflected by the mirror 402. Furthermore, the mirror 402 irradiates the excitation focusing lens 42, which will be described later, with the reflected light. The scanning drive unit 404 is an electrostatic drive actuator or an electromagnetic drive actuator, etc. When power is supplied to the scanning drive unit 404, the scanning semiconductor substrate 400 is driven. For example, the scanning semiconductor substrate 400 is rotated around an axis extending in one direction and an axis extending in a direction perpendicular to that direction. As a result, the scanning unit 40 is rotated around an axis extending in one direction and an axis extending in a direction perpendicular to that direction.
[0023] Returning to Figure 2, the excitation focusing lens 42 collects the reflected light from the scanning unit 40, i.e., the excitation light. Furthermore, the excitation focusing lens 42 irradiates the sample 90 coated with the reagent with the collected excitation light. This generates fluorescence, which is light emitted from the sample 90 and has a specific wavelength corresponding to the type of sample 90. In addition, the excitation focusing lens 42 makes it easier for the excitation light reflected by the scanning unit 40 to irradiate the reagent-coated sample 90 with pinpoint accuracy compared to when the excitation focusing lens 42 is not present.
[0024] The fluorescence focusing lens 44 collects the fluorescence. Furthermore, the fluorescence focusing lens 44 irradiates the collected fluorescence onto the fluorescence aperture section 46, which will be described later. In addition, the fluorescence focusing lens 44 makes it easier for the fluorescence to be precisely irradiated onto the fluorescence aperture section 46, which will be described later, compared to when the fluorescence focusing lens 44 is not present.
[0025] The fluorescence aperture section 46 is formed, for example, from a plate-shaped member. Furthermore, the fluorescence aperture section 46 has slits and pinholes. Fluorescence passes through the slits and pinholes of the fluorescence aperture section 46. As a result, the fluorescence aperture section 46 narrows the fluorescence, making it into a beam. Furthermore, the fluorescence aperture section 46 irradiates the narrowed fluorescence onto the fluorescence scattering section 48, which will be described later.
[0026] The fluorescence scattering section 48 is, for example, a MEMS diffraction grating. Specifically, as shown in Figure 5, the fluorescence scattering section 48 includes a fluorescence semiconductor substrate 480, a fluorescence surface area 482, and a fluorescence drive section 484, etc.
[0027] The fluorescence semiconductor substrate 480 is, for example, a silicon substrate. The length and width of the fluorescence semiconductor substrate 480 are, for example, 1 to 10 mm. Furthermore, the thickness of the fluorescence semiconductor substrate 480 is, for example, 0.2 to 1.0 mm. The fluorescence unevenness 482 is formed on the fluorescence semiconductor substrate 480. The fluorescence unevenness 482 scatters the fluorescence from the fluorescence aperture 46. Furthermore, the size of the fluorescence unevenness 482 is adjusted according to the reagent and the wavelength band of the fluorescence corresponding to it. The fluorescence drive unit 484 is an electrostatic drive actuator or an electromagnetic drive actuator, etc. When power is supplied to the fluorescence drive unit 484, the fluorescence semiconductor substrate 480 is driven. For example, the fluorescence semiconductor substrate 480 is rotated around an axis extending in one direction. As a result, the fluorescence scattering unit 48 is rotated around an axis extending in one direction.
[0028] Returning to Figure 2, the fluorescence passage section 50 is formed, for example, from a plate-shaped member. Furthermore, the fluorescence passage section 50 has slits and pinholes. Analytical fluorescence, which is a portion of the fluorescence scattered by the fluorescence scattering section 48, passes through the slits and pinholes of the fluorescence passage section 50. Furthermore, the fluorescence passage section 50 focuses the analytical fluorescence to form a beam. The fluorescence passage section 50 also irradiates the focused analytical fluorescence onto the light-receiving element 52, which will be described later.
[0029] The light-receiving element 52 is, for example, a SPAD. Furthermore, the light-receiving element 52 receives the analytical fluorescence that has passed through the fluorescence passage section 50. The light-receiving element 52 also outputs a signal, for example, a voltage, corresponding to the intensity of the analytical fluorescence to the control device 80 described later. SPAD stands for Single Photon Avalanche Diode.
[0030] Returning to Figure 1, the control device 80 is mainly composed of a microcontroller and includes a CPU, ROM, flash memory, RAM, I / O, drive circuit, A / D converter, and bus lines connecting these components. Furthermore, the control device 80 has a coating control unit 82 and an analysis unit 84 as functional blocks.
[0031] The coating control unit 82 controls the robot and nozzle of the coating apparatus 20 (not shown) based on an image of the sample 90 captured by a camera (not shown) by executing a program stored in the ROM of the coating control unit 82. This causes the coating control unit 82 to instruct the coating apparatus 20 to apply the reagent to the sample 90. The coating control unit 82 also outputs a signal to the analysis unit 84 (described later) indicating that the reagent has been applied to the sample 90.
[0032] The analysis unit 84 identifies the type of sample 90 based on the signal from the coating control unit 82 and the signal from the photodetector 52 by executing a program stored in the ROM of the analysis unit 84.
[0033] As described above, the sample analysis system 10 is configured as shown. Next, the control of the coating device 20 by the execution of the program of the coating control unit 82 will be explained with reference to the flowchart in Figure 6. The program of the coating control unit 82 is executed, for example, when the user starts the sample analysis system 10.
[0034] In step S100, the coating control unit 82 acquires an image of the sample 90 from a camera (not shown) that has captured the image. The image of the sample 90 is taken, for example, by the user of the sample analysis system 10.
[0035] Next, in step S102, if the camera (not shown) is a stereo camera, the coating control unit 82 calculates the position of the region containing the sample 90 relative to the camera by using the image of the sample 90 acquired in step S100 and triangulation. Alternatively, if the camera (not shown) is a monocular camera, the coating control unit 82 calculates the position of the region containing the sample 90 relative to the camera by using the image of the sample 90 acquired in step S100 and machine learning. The coating control unit 82 also outputs a signal to the analysis unit 84 corresponding to the calculated position of the region containing the sample 90 relative to the camera. Furthermore, the coating control unit 82 acquires the position of the nozzle of the coating device 20 relative to the camera, which is detected by a position sensor (not shown), etc. The coating control unit 82 also calculates the position of the region containing the sample 90 relative to the nozzle based on the calculated position of the region containing the sample 90 relative to the camera and the acquired position of the nozzle of the coating device 20 relative to the camera.
[0036] Next, in step S104, the coating control unit 82 controls a robot (not shown). This causes the coating control unit 82 to move the nozzle to the position of the region containing the sample 90 relative to the nozzle, as calculated in step S102. As a result, the nozzle approaches the region containing the sample 90. Furthermore, the coating control unit 82 opens the electromagnetic valve (not shown) of the nozzle by supplying power to it. This causes the reagent to be ejected from the nozzle. Therefore, the reagent is applied to the region containing the sample 90, and thus applied to the sample 90. The coating control unit 82 also outputs a signal to the analysis unit 84 indicating that the reagent has been applied to the sample 90, along with information about the applied reagent. After that, the processing of the coating control unit 82 ends.
[0037] As described above, the coating control unit 82 controls the coating apparatus 20. Next, the identification of the sample type 90 by executing the program of the analysis unit 84 will be explained with reference to the flowchart in Figure 7. The program of the analysis unit 84 is executed, for example, when the analysis unit 84 receives a signal from the coating control unit 82 indicating that it has applied the reagent to the sample 90.
[0038] In step S200, the analysis unit 84 acquires various information. Specifically, the analysis unit 84 acquires information such as the wavelength band of excitation light and fluorescence corresponding to the coated reagent from the coating control unit 82. The analysis unit 84 also acquires an image of the sample 90 coated with the reagent from the camera or the coating control unit 82. Furthermore, the analysis unit 84 acquires the position of the region including the sample 90 relative to the camera from the coating control unit 82. The analysis unit 84 also acquires the position of the scanning unit 40 relative to the camera, which is detected by a position sensor (not shown) or the like, from a position sensor (not shown). Furthermore, the analysis unit 84 calculates the position of the region including the sample 90 relative to the scanning unit 40 based on the acquired position of the region including the sample 90 relative to the camera and the position of the scanning unit 40 relative to the camera.
[0039] Next, in step S202, the analysis unit 84 controls the drive of the scanning unit 40. Specifically, the analysis unit 84 determines the power to supply to the scanning unit 40 by using the position of the region containing the sample 90 relative to the scanning unit 40 calculated in step S200 and the map. The analysis unit 84 then supplies this determined power to the scanning unit 40. This causes the scanning unit 40 to rotate. As a result, as shown in Figure 8, the light reflected by the scanning unit 40 passes through the excitation focusing lens 42 and irradiates the reagent-coated sample 90 with one pixel of the captured image and its surrounding pixels. The map for determining the power to supply to the scanning unit 40 is set through experiments or simulations so that the light reflected by the scanning unit 40 passes through the excitation focusing lens 42 and irradiates the reagent-coated sample 90. Furthermore, in Figure 8, the captured image is indicated by Im.
[0040] Furthermore, as will be described later, after fluorescence analysis is completed on one pixel of the captured image and its surrounding pixels of the sample 90, the analysis unit 84 changes the power supplied to the scanning unit 40. This causes the scanning unit 40 to rotate. For example, the light reflected by the scanning unit 40 is shifted by one pixel and its surrounding pixels in the X direction and irradiates the sample 90. Furthermore, after the light reflected by the scanning unit 40 has irradiated the captured image from one end to the other in the X direction, the light reflected by the scanning unit 40 is shifted by one pixel and its surrounding pixels in the Y direction and irradiates the sample 90 sequentially from one end in the X direction. These processes are repeated until the number of scans Ns becomes the total number of scans Ns_p. Note that the X direction is one direction of the captured image. The Y direction is perpendicular to the X direction. Furthermore, the number of scans Ns corresponds to the number of times the scanning unit 40 has been driven. Furthermore, the total number of scans Ns_p is the number of scans Ns until the light reflected by the scanning unit 40 irradiates all pixels of the captured image. For example, if the total number of pixels in the captured image is 1920 × 1080, and if the scanning unit 40 reflects light for 9 pixels each time it is driven, then the total number of scans Ns_p is 1920 × 1080 ÷ 9 = 230400.
[0041] Returning to the flowchart in Figure 7, in step S204, since the scanning unit 40 was driven to rotate in step S202, the analysis unit 84 calculates the current scan number Ns(n) by adding 1 to the previous scan number Ns(n-1). The initial scan number Ns(0) is, for example, zero.
[0042] Next, in step S206, the analysis unit 84 controls the drive of the excitation scattering unit 36. Specifically, the analysis unit 84 determines the power to supply to the excitation scattering unit 36 by using the wavelength band of the excitation light corresponding to the reagent acquired in step S200 and the map. The analysis unit 84 then supplies this determined power to the excitation scattering unit 36. As a result, the excitation scattering unit 36 rotates, as shown in Figure 2. This changes the wavelength of the excitation light passing through the excitation passage unit 38. The excitation light that has passed through the excitation passage unit 38 is reflected by the scanning unit 40. Furthermore, the light reflected by the scanning unit 40 passes through the excitation focusing lens 42 and irradiates the sample 90 coated with the reagent. At this time, fluorescence with a unique wavelength corresponding to the type of sample 90 is generated. This generated fluorescence then passes through the fluorescence focusing lens 44 and the fluorescence aperture unit 46. Furthermore, the fluorescence that has passed through the fluorescence focusing lens 44 and the fluorescence aperture 46 is scattered by the fluorescence scattering unit 48. These processes are repeated until the number of excitations Ne equals the total number of excitations Ne_p. As a result, the sample 90 coated with reagents is irradiated with excitation light of the wavelength corresponding to each reagent. The map for determining the power supplied to the excitation scattering unit 36 is set through experiments or simulations so that some of the light scattered by the excitation scattering unit 36, as well as excitation light having wavelengths corresponding to the reagents, passes through the excitation passing unit 38. The number of excitations Ne corresponds to the number of times the excitation scattering unit 36 is driven. Furthermore, the total number of excitations Ne_p corresponds to the number of wavelengths corresponding to the reagents.
[0043] Returning to the flowchart in Figure 7, in step S208, since the excitation scattering unit 36 was driven in step S206, the analysis unit 84 calculates the current excitation number Ne(n) by adding 1 to the previous excitation number Ne(n-1). The initial excitation number Ne(0) is, for example, zero.
[0044] Next, in step S210, the analysis unit 84 controls the drive of the fluorescence scattering unit 48. Specifically, the analysis unit 84 determines the power to supply to the fluorescence scattering unit 48 by using the wavelength band of fluorescence corresponding to the reagent acquired in step S200 and the map. The analysis unit 84 then supplies this determined power to the fluorescence scattering unit 48. As a result, the fluorescence scattering unit 48 rotates, as shown in Figure 2. This changes the wavelength of the analytical fluorescence passing through the fluorescence passage unit 50. The analytical fluorescence that has passed through the fluorescence passage unit 50 is received by the photodetector 52. Furthermore, the photodetector 52 outputs a signal to the analysis unit 84 corresponding to the intensity of the received analytical fluorescence. The analysis unit 84 also acquires a signal corresponding to the intensity of the analytical fluorescence from the photodetector 52.
[0045] Next, in step S212, the analysis unit 84 identifies the type of sample 90 by analyzing the intensity of the analytical fluorescence acquired in step S210. Specifically, the analysis unit 84 determines whether the intensity of the analytical fluorescence acquired in step S210 is a peak value. If the intensity of the analytical fluorescence is not a peak value, the sample 90 cannot be identified, and the analysis unit 84 proceeds to step S214. When the intensity of the analytical fluorescence is a peak value, the wavelength at this time is the wavelength of the unique fluorescence produced by the sample 90. Therefore, at this time, the analysis unit 84 identifies the type of sample 90 by using the wavelength corresponding to the peak value and a map. Furthermore, the process from step S210 to step S212 is repeated until the number of fluorescence occurrences Nf becomes the total number of fluorescence occurrences Nf_p, thereby generating waveforms of light intensity for analytical wavelengths as shown in Figures 9 and 10. The map for identifying the type of sample 90 is set through experiments or simulations so that the type of sample 90 can be identified from the peak value of the analytical fluorescence intensity. Furthermore, the fluorescence count Nf corresponds to the number of times the fluorescence scattering unit 48 is driven. In addition, the total fluorescence count Nf_p corresponds to the value obtained by dividing the fluorescence wavelength band corresponding to the reagent by the analytical fluorescence wavelength band that passes through the fluorescence passing unit 50. The fluorescence wavelength band corresponding to the reagent is represented by Em in Figure 7, and is, for example, 400 to 600 nm. Furthermore, the analytical fluorescence wavelength band that passes through the fluorescence passing unit 50 corresponds to the resolution R for detecting the intensity of the analytical fluorescence, and is, for example, 1 nm. Figure 9 shows the case where one type of sample 90 is identified in one pixel and its surrounding pixels. Furthermore, in Figure 9, the wavelength at which the peak value corresponding to one type of sample 90 is obtained is shown as λ. Furthermore, Figure 10 shows the case where two types of samples 90 are identified in one pixel and its surrounding pixels. Furthermore, in Figure 10, the wavelength at which the peak value corresponding to one type of sample 90 is obtained is shown as λ1. Furthermore, the wavelength at which the peak value corresponding to the other type of sample 90 is obtained is shown as λ2.
[0046] Next, in step S214, since the fluorescence scattering unit 48 was driven to rotate in step S210, the analysis unit 84 calculates the current fluorescence count Nf(n) by adding 1 to the previous fluorescence count Nf(n-1). The initial fluorescence count Nf(0) is, for example, zero.
[0047] Next, in step S216, the analysis unit 84 determines whether the current fluorescence count Nf(n) calculated in step S214 is the total fluorescence count Nf_p. Based on this, the analysis unit 84 determines whether the fluorescence analysis has been completed for one reagent applied to one pixel and its surrounding pixels in the sample 90.
[0048] If the current fluorescence count Nf(n) is not equal to the total fluorescence count Nf_p, the fluorescence analysis has not been completed for the one reagent applied to one pixel and its surrounding pixels in the sample 90, so the analysis unit 84 returns to step S210. When the analysis unit 84 returns to step S210, the processes from step S210 to step S212 are repeated until the current fluorescence count Nf(n) becomes equal to the total fluorescence count Nf_p. Furthermore, when the current fluorescence count Nf(n) is equal to the total fluorescence count Nf_p, the fluorescence analysis has been completed for the one reagent applied to one pixel and its surrounding pixels in the sample 90, so the analysis unit 84 proceeds to step S218.
[0049] In step S218, following step S216, since fluorescence analysis has been completed for one reagent applied to one pixel and its surrounding pixels in the sample 90, the analysis unit 84 resets the current fluorescence count Nf(n). For example, the analysis unit 84 sets the current fluorescence count Nf(n) to zero. This allows fluorescence analysis to be performed on a different reagent applied to the sample 90 of that pixel.
[0050] Next, in step S220, the analysis unit 84 determines whether the current excitation count Ne(n) calculated in step S208 is the total excitation count Ne_p. Based on this, the analysis unit 84 determines whether fluorescence analysis has been completed for all types of reagents coated on one pixel and its surrounding pixels in the sample 90.
[0051] Then, when the current excitation count Ne(n) is not equal to the total excitation count Ne_p, fluorescence analysis has not been completed for all types of reagents applied to one pixel and its surrounding pixels in the sample 90, so the analysis unit 84 returns to step S206. When the analysis unit 84 returns to step S206, the processes from step S206 to step S218 are repeated until the current excitation count Ne(n) becomes equal to the total excitation count Ne_p. Furthermore, when the current excitation count Ne(n) is equal to the total excitation count Ne_p, fluorescence analysis has been completed for all types of reagents applied to one pixel and its surrounding pixels in the sample 90, so the analysis unit 84 proceeds to step S222.
[0052] In step S222, following step S220, since fluorescence analysis has been completed for all types of reagents applied to one pixel and its surrounding pixels in the sample 90, the analysis unit 84 resets the current excitation count Ne(n). For example, the analysis unit 84 sets the current excitation count Ne(n) to zero. This allows the fluorescence analysis to be performed on the pixels of the sample 90 that have not yet undergone fluorescence analysis.
[0053] Next, in step S224, the analysis unit 84 determines whether the current scan number Ns(n) calculated in step S204 is equal to the total scan number Ns_p. Based on this, the analysis unit 84 determines whether fluorescence analysis has been completed for all pixels of the sample 90.
[0054] When the current scan count Ns(n) is not equal to the total scan count Ns_p, fluorescence analysis has not been completed for all pixels of the sample 90, so the analysis unit 84 returns to step S202. At this time, as described above, in step S202, the analysis unit 84 changes the power supplied to the scanning unit 40. This causes the scanning unit 40 to rotate. As a result, the light reflected by the scanning unit 40 irradiates the pixels of the sample 90 that have not been subjected to fluorescence analysis. When the analysis unit 84 returns to step S202, the process from step S202 to step S222 is repeated until the current scan count Ns(n) becomes equal to the total scan count Ns_p.
[0055] Furthermore, when the current scan count Ns(n) is equal to the total scan count Ns_p, fluorescence analysis has been completed for all pixels of the sample 90, and the analysis unit 84 terminates its processing. At this time, the analysis unit 84 resets the current scan count Ns(n). For example, the analysis unit 84 sets the current scan count Ns(n) to zero. As a result of this initialization, the analysis unit 84 can identify the type of sample 90 in the next scan in the same manner as described above.
[0056] As described above, the analysis unit 84 identifies the type of sample 90. Next, in the sample analysis system 10 using the spectrometer 30 of this embodiment, it will be explained that the wavelength of the excitation light changes continuously while the excitation light is irradiated.
[0057] The spectrometer 30 comprises a light source 32, an excitation scattering unit 36, an excitation passing unit 38, a scanning unit 40, a fluorescence scattering unit 48, a fluorescence passing unit 50, and a photodetector 52. The sample analysis system 10 also comprises an analysis unit 84. The light source 32 emits light having multiple wavelengths. The excitation scattering unit 36 scatters the light from the light source 32. The excitation passing unit 38 allows some of the light scattered by the excitation scattering unit 36, which is the excitation light, to pass through. The scanning unit 40 reflects the excitation light that has passed through the excitation passing unit 38 and irradiates the sample 90 coated with a reagent with the reflected light, thereby generating fluorescence, which is the light emitted by the sample 90. The fluorescence scattering unit 48 scatters the fluorescence. The fluorescence passing unit 50 allows some of the fluorescence scattered by the fluorescence scattering unit 48, which is the analytical fluorescence, to pass through. The light-receiving element 52 receives the analytical fluorescence that has passed through the fluorescence passage section 50 and outputs a signal corresponding to the intensity of the analytical fluorescence. In step S206, the analysis section 84 drives the excitation scattering section 36, thereby changing the excitation light that passes through the excitation passage section 38, and thus acts as an excitation modification section that changes the wavelength of the excitation light reflected by the scanning section 40.
[0058] When the excitation scattering unit 36 is driven, the wavelength of the excitation light reflected by the scanning unit 40 is changed. As a result, the wavelength of the excitation light changes continuously while the excitation light is being irradiated.
[0059] Furthermore, the sample analysis system 10 using the spectrometer 30 of this embodiment also provides the following effects.
[0060] [1] In step S202, the analysis unit 84 drives the scanning unit 40 to change the irradiation position of the reflected light, thereby acting as a scanning modification unit.
[0061] This makes it easier for reflected light to irradiate the sample 90. Furthermore, it suppresses irradiation of other objects, such as the walls and furniture inside a car or house to which the sample 90 is attached.
[0062] [2] In step S210, the analysis unit 84 drives the fluorescence scattering unit 48 to change the analytical fluorescence passing through the fluorescence passage unit 50, thereby acting as a fluorescence changing unit that changes the wavelength of the analytical fluorescence received by the photodetector 52.
[0063] When the fluorescence scattering unit 48 is driven, the wavelength of the analytical fluorescence received by the photodetector 52 is changed. Therefore, the wavelength of the fluorescence changes continuously while the fluorescence is being irradiated. As a result, the photodetector 52 outputs a signal corresponding to the intensity of each wavelength of fluorescence. This makes it easier to analyze the wavelengths of the fluorescence.
[0064] [3] The excitation scattering section 36 is a MEMS diffraction grating and includes an excitation semiconductor substrate 360, an excitation surface section 362, and an excitation drive section 364.
[0065] This allows the excitation scattering unit 36 to be formed using MEMS technology. As a result, the excitation scattering unit 36 can be miniaturized. Consequently, the spectrometer 30 and the sample analysis system 10 can be miniaturized.
[0066] [4] The fluorescence scattering section 48 is a MEMS diffraction grating and includes a fluorescence semiconductor substrate 480, a fluorescence uneven section 482, and a fluorescence driving section 484.
[0067] This allows the fluorescence scattering section 48 to be formed using MEMS technology. As a result, the fluorescence scattering section 48 can be miniaturized. Consequently, the spectrometer 30 and the sample analysis system 10 can be miniaturized.
[0068] [5] The scanning unit 40 is a MEMS scanner and includes a scanning semiconductor substrate 400, a mirror 402, and a scanning drive unit 404.
[0069] This allows the scanning unit 40 to be formed using MEMS technology. As a result, the scanning unit 40 can be miniaturized. Consequently, the spectrometer 30 and the sample analysis system 10 can be miniaturized.
[0070] [6] As shown in Figure 2, when reflected light from the scanning unit 40 is irradiated onto the walls and furniture inside the car or house to which the sample 90 is attached, the reflected light and fluorescence from the walls and furniture inside the car or house are received by the photodetector 52. At this time, since the fluorescence from the sample 90 is received by the photodetector 52, the reflected light and fluorescence from the walls and furniture inside the car or house become noise. As a result, the accuracy of the signal output from the photodetector 52 decreases. Consequently, the accuracy of identification by the analysis unit 84 decreases. In Figure 2, the noise from the walls and furniture inside the car or house to which the sample 90 is attached is shown as Nb.
[0071] In contrast, in this embodiment, the excitation aperture 34 focuses the light from the light source 32 and irradiates the excitation scattering unit 36 with the focused light. The excitation scattering unit 36 then scatters the light focused by the excitation aperture 34.
[0072] The excitation aperture 34 makes it easier for the light from the light source 32 to become beam-shaped. As a result, the beam-shaped light is scattered by the excitation scattering unit 36. Therefore, the scattered beam-shaped excitation light passes through the excitation passing unit 38. The beam-shaped excitation light that has passed through the excitation passing unit 38 is reflected by the scanning unit 40. Furthermore, the beam-shaped reflected light is irradiated onto the sample 90. Therefore, the excitation light is more likely to be irradiated onto the sample 90 with pinpoint accuracy. Consequently, the irradiation of the excitation light onto the walls and furniture inside the car or house is suppressed, thus reducing noise. This suppresses a decrease in the accuracy of the signal output from the photodetector 52. Therefore, a decrease in the accuracy of identification by the analysis unit 84 is suppressed.
[0073] [7] The fluorescence aperture 46 narrows the fluorescence and irradiates the fluorescence scattering unit 48 with the narrowed light. The fluorescence scattering unit 48 also scatters the light narrowed by the fluorescence aperture 46.
[0074] The fluorescence aperture 46 makes it easier for fluorescence to be precisely irradiated onto the fluorescence scattering section 48. This suppresses noise generated by fluorescence irradiating areas other than the fluorescence scattering section 48. As a result, the reduction in accuracy of the analytical fluorescence received by the photodetector 52 via the fluorescence passage section 50 from the fluorescence scattering section 48 is suppressed. Consequently, the reduction in accuracy of the signal output from the photodetector 52 is suppressed. Consequently, the reduction in the accuracy of identification by the analysis section 84 is suppressed.
[0075] (Other embodiments) This disclosure is not limited to the embodiments described above, and modifications can be made to these embodiments as appropriate. Furthermore, it goes without saying that, in each of the embodiments described above, the elements constituting the embodiment are not necessarily essential, except in cases where they are explicitly stated to be particularly essential or where they are clearly considered essential in principle.
[0076] The modifications and methods described in this disclosure may be implemented by a dedicated computer provided by configuring a processor and memory programmed to perform one or more functions embodied by a computer program. Alternatively, the modifications and methods described in this disclosure may be implemented by a dedicated computer provided by configuring a processor by one or more dedicated hardware logic circuits. Alternatively, the modifications and methods described in this disclosure may be implemented by one or more dedicated computers configured by a combination of a processor and memory programmed to perform one or more functions and a processor configured by one or more hardware logic circuits. Furthermore, the computer program may be stored as instructions executed by the computer on a computer-readable non-transitional tangible recording medium.
[0077] In the above embodiment, the excitation scattering section 36 and the fluorescence scattering section 48 are MEMS diffraction gratings, but are not limited to these. For example, the excitation scattering section 36 and the fluorescence scattering section 48 may be optical filters, diffraction gratings and prisms that do not use MEMS technology, etc. In these cases, the excitation scattering section 36 and the fluorescence scattering section 48 are rotated by a motor or the like around an axis that extends in one direction.
[0078] In the above embodiment, the scanning unit 40 is a MEMS scanner, but is not limited to this. For example, the scanning unit 40 may be a galvanometer mirror or the like. In this case, the scanning unit 40 is rotated by a motor or the like around an axis extending in one direction and an axis extending in a direction perpendicular to that direction.
[0079] In the above embodiment, the excitation scattering unit 36, the scanning unit 40, and the fluorescence scattering unit 48 are rotationally driven, but are not limited to this. For example, the excitation scattering unit 36, the scanning unit 40, and the fluorescence scattering unit 48 may be driven by oscillation or the like. [Explanation of symbols]
[0080] 32 light source 34 Excitation aperture section 36 Excitation scattering section 38 Excitation passage section 40 Scanning Unit 46 Fluorescent aperture section 48 Fluorescence scattering part 50 Fluorescent passage section 52 Photodetector 84 Analysis Department
Claims
1. A light source (32) that emits light having multiple wavelengths, An excitation scattering unit (36) that scatters light from the aforementioned light source, An excitation passing section (38) that allows some of the light scattered by the excitation scattering section, which is excitation light, to pass through, A scanning unit (40) that reflects the excitation light that has passed through the excitation passage and irradiates the reagent-coated sample (90) with the reflected light to generate fluorescence, which is light emitted by the sample, A fluorescence scattering unit (48) that scatters the aforementioned fluorescence, A fluorescence passage section (50) that allows a portion of the fluorescence scattered by the fluorescence scattering section to pass through, which is the analytical fluorescence, A light-receiving element (52) that receives the analytical fluorescence that has passed through the fluorescence passage and outputs a signal corresponding to the intensity of the analytical fluorescence, An excitation modification unit (S206) changes the wavelength of the excitation light reflected by the scanning unit by driving the excitation scattering unit and thereby changing the excitation light passing through the excitation passage unit, A spectroscopic apparatus equipped with the following features.
2. The spectroscopic apparatus according to claim 1, further comprising a scanning modification unit (S202) that changes the irradiation position of the reflected light by driving the scanning unit.
3. The scanning unit, A scanning semiconductor substrate (400) and A mirror (402) formed on the scanning semiconductor substrate that reflects the excitation light, When power is supplied, a scanning drive unit (404) drives the scanning semiconductor substrate, It has, The spectroscopic apparatus according to claim 2, wherein the scanning modification unit controls the drive of the scanning unit by controlling the power supplied to the scanning drive unit.
4. The spectroscopic apparatus according to claim 1 or 2, further comprising a fluorescence changing unit (S210) that changes the wavelength of the analytical fluorescence received by the photodetector by driving the fluorescence scattering unit and thereby changing the analytical fluorescence passing through the fluorescence passing unit.
5. The aforementioned fluorescence scattering section is A semiconductor substrate for fluorescence (480), The fluorescent semiconductor substrate has a fluorescent uneven portion (482) formed thereon, which scatters light from the light source due to its uneven surface, When power is supplied, a fluorescence drive unit (484) drives the fluorescence semiconductor substrate, It has, The spectroscopic apparatus according to claim 4, wherein the fluorescence changing unit controls the driving of the fluorescence scattering unit by controlling the power supplied to the fluorescence driving unit.
6. The excitation scattering unit is, Excitation semiconductor substrate (360), The excitation semiconductor substrate has an excitation surface (362) formed thereon, which scatters light from the light source due to its surface irregularities, When power is supplied, an excitation drive unit (364) drives the excitation semiconductor substrate, It has, The spectroscopic apparatus according to claim 1 or 2, wherein the excitation modification unit controls the driving of the excitation scattering unit by controlling the power supplied to the excitation drive unit.
7. The spectroscopic apparatus further comprises an excitation aperture (34) that focuses the light from the light source and irradiates the excitation scattering section with the focused light, The spectroscopic apparatus according to claim 1 or 2, wherein the excitation scattering unit scatters the light focused by the excitation aperture unit.
8. The spectrometer further comprises a fluorescence aperture (46) that focuses the fluorescence and irradiates the fluorescence scattering section with the focused light, The spectroscopic apparatus according to claim 1 or 2, wherein the fluorescence scattering section scatters the light focused by the fluorescence aperture section.
9. A spectrometer (30) comprising: a light source (32) that emits light having multiple wavelengths; an excitation scattering unit (36) that scatters light from the light source; an excitation passing unit (38) that allows a portion of the light scattered by the excitation scattering unit, which is excitation light, to pass through; a scanning unit (40) that reflects the excitation light that has passed through the excitation passing unit and irradiates a sample (90) coated with a reagent with the reflected light to generate fluorescence, which is light emitted by the sample; a fluorescence scattering unit (48) that scatters the fluorescence; a fluorescence passing unit (50) that allows a portion of the fluorescence scattered by the fluorescence scattering unit, which is analytical fluorescence, to pass through; a photodetector (52) that receives the analytical fluorescence that has passed through the fluorescence passing unit and outputs a signal corresponding to the intensity of the analytical fluorescence; and an excitation changing unit (S206) that changes the wavelength of the excitation light reflected by the scanning unit by changing the excitation light that passes through the excitation passing unit by driving the excitation scattering unit. An analytical unit (84) that identifies the type of sample based on the intensity of the aforementioned analytical fluorescence, A sample analysis system equipped with the following features.
10. The sample analysis system according to claim 9, further comprising a coating device (20) for coating the sample with the reagent.
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