AUTOMATIC ANALYSIS DEVICE
20220397581 · 2022-12-15
Assignee
Inventors
- Takahiro ANDO (Tokyo, JP)
- Sakuichiro Adachi (Tokyo, JP)
- Yasuhiro KETA (Tokyo, JP)
- Yuya MATSUOKA (Tokyo, JP)
- Hiromitsu MORI (Tokyo, JP)
- Shin IMAMURA (Tokyo, JP)
- Eiichiro TAKADA (Tokyo, JP)
- Makoto Arai (Tokyo, JP)
Cpc classification
International classification
G01N35/00
PHYSICS
Abstract
Provided is an automatic analysis device capable of obtaining a stable light intensity over a wide wavelength band by multiplexing a plurality of LED lights and adjusting the temperature characteristics of each LED element. The automatic analysis device according to the present disclosure is configured such that light emitted from a second LED is reflected to be multiplexed on the same optical axis as the light emitted from a first LED, and the first LED and the second LED are in contact with the same temperature adjustment member.
Claims
1. An automatic analysis device for measuring a sample, comprising: a light source for irradiating a reaction vessel storing the sample with light, and a temperature adjustment mechanism for adjusting the temperature of the light source, wherein the light source includes a first LED and a second LED, wherein the light source is configured such that light emitted from the second LED is reflected on a reflective element to change an optical path, thereby the light emitted from the second LED is multiplexed with light emitted from the first LED on a same optical axis as that of light emitted from the first LED, and wherein the temperature adjustment mechanism is configured by a member that is in contact with the first LED and the second LED respectively.
2. The automatic analysis device according to claim 1, wherein a light intensity of the second LED is larger than a light intensity of the first LED, wherein the light source further includes: a first optical element that allows at least a part of first light emitted from the first LED to pass; and a second optical element that reflects second light emitted from the second LED, wherein the first optical element is configured to reflect at least a part of the second light, and wherein the first optical element and the second optical element are arranged such that the first light having passed through the first optical element and the second light reflected by the first optical element are multiplexed on a same optical axis to become multiplexed light.
3. The automatic analysis device according to claim 2, wherein the first LED is a white LED that generates white light in a wavelength range of 350 nm to 800 nm, and wherein the second LED is an ultraviolet LED that generates ultraviolet light having a central wavelength of 350 nm or less.
4. The automatic analysis device according to claim 1, wherein the temperature adjustment mechanism is configured by: one LED mounting substrate for mounting the first LED and the second LED; and a temperature adjustment unit that adjusts a temperature of the LED mounting substrate to keep a temperature difference between the first LED and the second LED within a predetermined range.
5. The automatic analysis device according to claim 2, further comprising: a diffusion member for diffusing the second light.
6. The automatic analysis device according to claim 5, wherein the first light is diffused within a first diffusion range on a light receiving surface of a light receiver that receives the multiplexed light, wherein the second light is diffused within a second diffusion range on the light receiving surface, and wherein the diffusion member diffuses the second light such that the first diffusion range is included in the second diffusion range.
7. The automatic analysis device according to claim 5, wherein the diffusion member is configured by a diffusion plate that is arranged between the second LED and the second optical element and that diffuses the second light.
8. The automatic analysis device according to claim 5, wherein the diffusion member is formed on a reflection surface of the second optical element by processing the reflection surface of the second optical element so as to diffuse the second light.
9. The automatic analysis device according to claim 2, wherein a transmittance at which the first optical element allows the first light to pass is configured such that, on a wavelength spectrum of the multiplexed light: a first wavelength component has a first light intensity; a second wavelength component has a second light intensity; and a third wavelength component has a third light intensity, and wherein when on a wavelength spectrum of light emitted from a halogen lamp, the first wavelength component has a fourth light intensity, the second wavelength component has a fifth light intensity, and the third wavelength component has a sixth light intensity, the first optical element is configured such that: a difference between a first ratio of the second light intensity to the first light intensity and a second ratio of the fifth light intensity to the fourth light intensity is within an allowable range; and a difference between a third ratio of the third light intensity to the second light intensity and a fourth ratio of the sixth light intensity to the fifth light intensity is within the allowable range.
10. The automatic analysis device according to claim 1, further comprising: a control unit for adjusting an intensity of light emitted by the light source by adjusting a drive current of the light source and a temperature of the temperature adjustment mechanism.
11. The automatic analysis device according to claim 10, wherein the control unit acquires temperature changes over time in an environment in which the automatic analysis device is installed, and wherein the control unit sets a target temperature of the temperature adjustment mechanism according to the temperature changes over time.
12. An automatic analysis device for measuring a sample, the device comprising: a light source for irradiating a reaction vessel storing the sample with light, wherein the light source includes: a first LED and a second LED; a first optical element that allows at least a part of first light emitted from the first LED to pass; and a second optical element that reflects second light emitted from the second LED, wherein the first optical element is configured to reflect at least a part of the second light, wherein the first optical element and the second optical element are arranged such that the first light having passed through the first optical element and the second light reflected by the first optical element are multiplexed on a same optical axis to become multiplexed light, wherein a transmittance at which the first optical element allows the first light to pass is configured such that, on a wavelength spectrum of the multiplexed light: a first wavelength component has a first light intensity; a second wavelength component has a second light intensity; and a third wavelength component has a third light intensity, and wherein when on a wavelength spectrum of light emitted from a halogen lamp, the first wavelength component has a fourth light intensity, the second wavelength component has a fifth light intensity, and the third wavelength component has a sixth light intensity, the first optical element is configured such that: a difference between a first ratio of the second light intensity to the first light intensity and a second ratio of the fifth light intensity to the fourth light intensity is within an allowable range; and a difference between a third ratio of the third light intensity to the second light intensity and a fourth ratio of the sixth light intensity to the fifth light intensity is within the allowable range.
Description
BRIEF DESCRIPTION OF DRAWINGS
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DESCRIPTION OF EMBODIMENTS
First Embodiment
[0028]
[0029] The dispensing mechanism moves a sample or a reagent between the disks. The control circuit 201 controls each disk and the dispensing mechanism. The light intensity measurement circuit 202 measures an absorbance of a reaction solution. The data processing unit 203 processes data measured by the light intensity measurement circuit 202. The input unit 204 and the output unit 205 are interfaces with the data processing unit 203. The dispensing mechanism includes a sample dispensing mechanism 110 and a reagent dispensing mechanism 111.
[0030] The data processing unit 203 includes an information recording unit 2031 and an analysis unit 2032. The information recording unit 2031 stores control data, measurement data, data to be used for data analysis, analysis result data, and the like. The data processing unit 203 may be realized using a computer. The computer includes at least a processor such as a central processing unit (CPU) and the information recording unit 2031. The processing of the analysis unit 2032 may be realized by storing program codes corresponding to the data processing in the information recording unit 2031 and by the processor executing the program codes.
[0031] The input unit 204 and the output unit 205 input and output data to and from the information recording unit 2031. The input unit 204 can be configured by an information input device such as a keyboard, a touch panel, or a numeric keypad. The output unit 205 is a device for a user of the automatic analyzer 10 to confirm the analysis results. The output unit 205 is, for example, a display or the like.
[0032] On a circumference in the sample disk 103, a plurality of sample cups 102, which are vessels for storing a sample 101, are arranged. The sample 101 is, for example, blood. On a circumference in the reagent disk 106, a plurality of reagent bottles 105, which are vessels for storing a reagent 104, are arranged. On a circumference in the reaction disk 109, a plurality of reaction cells 108 (reaction vessels), which are vessels for storing a reaction solution 107 obtained by mixing the sample 101 and the reagent 104, are arranged.
[0033] The sample dispensing mechanism 110 is a mechanism to be used when a certain amount of the sample 101 is moved from the sample cup 102 to the reaction cell 108. The sample dispensing mechanism 110 includes, for example, a nozzle that discharges or sucks a solution, a robot that positions and conveys the nozzle at a predetermined position, a pump that discharges or sucks a solution to or from the nozzle, and a flow path connecting the nozzle and the pump.
[0034] The reagent dispensing mechanism 111 is a mechanism to be used when a certain amount of the reagent 104 is moved from the reagent bottle 105 to the reaction cell 108. The reagent dispensing mechanism 111 also includes, for example, a nozzle that discharges or sucks a solution, a robot that positions and conveys the nozzle at a predetermined position, a pump that discharges or sucks a solution to or from the nozzle, and a flow path connecting the nozzle and the pump.
[0035] An agitating unit 112 is a mechanism unit that agitates and mixes the sample 101 and the reagent 104 in the reaction cell 108. A cleaning unit 114 is a mechanism unit that discharges the reaction solution 107 from the reaction cell 108 where the analysis process is completed, and then cleans the reaction cell 108. The next sample 101 is dispensed again from the sample dispensing mechanism 110 into the cleaned reaction cell 108, and a new reagent 104 is dispensed from the reagent dispensing mechanism 111. The reaction cell 108 is thereby used for another reaction processing.
[0036] In the reaction disk 109, the reaction cell 108 is immersed in a constant temperature fluid 115 in a constant temperature bath whose temperature and flow rate are controlled. As a result, the temperatures of the reaction cell 108 and of the reaction solution 107 therein are kept at a constant temperature by the control circuit 201 even while they are being moved by the reaction disk 109. Water or air, for example, is used for the constant temperature fluid 115.
[0037] An absorbance measurement unit (absorption photometer) 113 that performs absorption analysis on the sample 101 is arranged on a part of the circumference in the reaction disk 109.
[0038]
[0039] The light transmitted through the reaction solution 107 in the reaction cell 108 is separated by a diffraction grating 3021 in a spectroscope 302, and is received by a detector array 3022 including a large number of light receivers. At this time, the light that has not passed through the reaction solution 107 becomes noise. Therefore, a spectrometer side slit 404 may be arranged to prevent such stray light from entering the spectroscope 302.
[0040] Examples of the measurement wavelength of the light received by the detector array 3022 include 340 nm, 376 nm, 405 nm, 415 nm, 450 nm, 480 nm, 505 nm, 546 nm, 570 nm, 600 nm, 660 nm, 700 nm, 750 nm, and 800 nm. The reception signals of the lights received by these light receivers are transmitted to the information recording unit 2031 of the data processing unit 203 through the light intensity measurement circuit 202.
[0041] The amounts of components, such as proteins, glucose, and lipids, contained in the sample 101 are calculated by the following procedure. First, the control circuit 201 instructs the cleaning unit 114 to clean the reaction cell 108. Next, the control circuit 201 causes the sample dispensing mechanism 110 to dispense a certain amount of the sample 101 in the sample cup 102 into the reaction cell 108. Next, the control circuit 201 causes the reagent dispensing mechanism 111 to dispense a certain amount of the reagent 104 in the reagent bottle 105 into the reaction cell 108.
[0042] When the respective solutions are dispensed, the control circuit 201 causes drive units, respectively corresponding to the disks, to rotationally drive the sample disk 103, the reagent disk 106, and the reaction disk 109. At this time, the sample cup 102, the reagent bottle 105, and the reaction cell 108 are positioned at predetermined dispensing positions according to drive timings of the corresponding dispensing mechanisms respectively.
[0043] Subsequently, the control circuit 201 controls the agitating unit 112 to agitate the sample 101 and the reagent 104 dispensed into the reaction cell 108, thereby generating the reaction solution 107. By the rotation of the reaction disk 109, the reaction cell 108 storing the reaction solution 107 passes through a measurement position where the absorbance measurement unit 113 is arranged. Each time passing through the measurement position, the intensity of the light transmitted from the reaction solution 107 is measured via the absorbance measurement unit 113. The measured data is sequentially output to the information recording unit 2031 and is accumulated as reaction process data.
[0044] During the accumulation of the reaction process data, another reagent 104, if necessary, is additionally dispensed into the reaction cell 108 by the reagent dispensing mechanism 111, and is agitated by the agitating unit 112, and measurement is further performed for a certain period of time. As a result, the reaction process data acquired at constant time intervals are stored in the information recording unit 2031.
[0045]
[0046] As the temperature adjustment unit 504, a metal block through which a constant temperature fluid flows, or a Peltier element, for example, can be used. In the case of a Peltier element, the LED side of the temperature adjustment unit 504 (the back surface of the LED mounting substrate 503) can be controlled to, for example, about 37±0.01° C. via the control circuit 201 by feedback control of the temperature sensor 505. According to this configuration, the element temperature of the first LED 501 and the element temperature of the second LED 502 are equivalent in a certain range. Then it is possible to perform quantitative analysis with high accuracy when the automatic analyzer 10 perform the two-wavelength measurement method.
[0047] On the other hand, when the first LED 501 and the second LED 502 are mounted on one piece of LED mounting substrate 503, a strict design tolerance is required in order to make the optical axes of the two LEDs match each other. Design tolerances are required not only for the position of the light emitting element of the LED and the mounting position of the package of the LED on the substrate, but also for a filter and a mirror to be used for multiplexing the two LED lights.
[0048] In the first embodiment, LED light in a wavelength band whose light intensity is not sufficient is used as the first LED 501 to secure a light intensity by making the LED light linearly incident on the spectroscope 302, and LED light in a wavelength band whose light intensity is sufficient is used as the second LED 502 to make the LED light incident on the spectroscope 302 through two-step reflection, as shown in
[0049] The light emitted from the second LED 502 is reflected in two steps on each of the reflector 507 and the dichroic filter 506, is then multiplexed with the light emitted from the first LED 501, and is incident on the spectroscope 302 through a path along the optical axis 401. At this time, it is desirable that: only the optical axis of the first LED 501 is designed to match the optical axis 401 of light to be incident on the spectroscope 302; and the light emitted from the second LED 502 is made incident after its luminous flux range is expanded by a diffusion plate. Details will be described in a second embodiment.
[0050]
[0051] As shown in the graphs of
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First Embodiment: Summary
[0053] In the automatic analyzer 10 according to the first embodiment, a light intensity is secured by making LED light (the first LED 501) in a wavelength band whose light intensity is not sufficient linearly incident on an analysis unit; and a constant attenuation in the light intensity of LED light (the second LED 502) in a wavelength band whose light intensity is sufficient is allowable, so that the LED light is multiplexed with the light emitted from the first LED 501 by two-step reflection. As a result, a wide wavelength range can be secured and a light intensity can be secured, so that high analysis performance can be maintained over a wide wavelength range.
[0054] In the automatic analyzer 10 according to the first embodiment, the first LED 501 and the second LED 502 are mounted on one LED mounting substrate 503, and the temperature of the LED mounting substrate 503 is controlled by the temperature adjustment unit 504. As a result, the temperature of the first LED 501 and the temperature of the second LED 502 can be controlled to be substantially the same, and a light intensity fluctuation difference between the LEDs can be suppressed. Therefore, in the limited internal space of the automatic analyzer 10, a stable light intensity can be obtained while the space of the temperature adjustment unit 504 is suppressed.
Second Embodiment
[0055]
[0056] When the effective light emitting area of a LED light source is set to 1.0 mm square, it is necessary to design such that only the optical axis of the first LED 501 matches the optical axis 401 of the light to be incident on the spectroscope 302 in order to obtain a light intensity that enables quantitative analysis with high accuracy. In this case, however, it is difficult to match the optical axis of the light emitted from the second LED 502 with the optical axis 401 of the light to be incident on the spectroscope 302. Then, it becomes difficult to match, between the LEDs, the optical axes and the light intensity distributions for a reaction solution. This may decrease the measurement accuracy of the two-wavelength measurement method. Therefore, in the second embodiment, a diffusion plate 508 that expands the effective light emitting area of the second LED 502 is arranged before the reflector 507 on which light is incident.
[0057]
[0058] When the diffusion plate 508 is used, the light emitted from the second LED 502 is diffused in a range 502B that encompasses the range 501A. As a result, both the emitted lights overlap each other on the light receiving surface 302A, and the in-plane distribution of the light intensity can be made uniform on the light receiving surface 302A. That is, the diffusion plate 508 is desirably configured such that the range 502B encompasses the range 501A on light receiving surface 302A.
[0059]
[0060]
[0061] The multiplexed light of the first LED 501 and the second LED 502 has a spectrum as indicated, for example, by a solid line in
[0062] When the halogen lamp is compared with the multiplexed light after transmission, the multiplexed light after transmission has a wavelength band in which the light intensity is insufficient. An increase in the LED light intensity can be expected by the temperature adjustment unit 504 lowering the temperature of the LED element. As a result, the light intensity of the multiplexed light after transmission can be increased over the entire spectrum range, and the spectrum can be further made closer to the halogen lamp. For example, a general ultraviolet LED has a light intensity fluctuation of about 5% in all wavelengths when the temperature is changed by 10° C.
[0063]
[0064] The spectrum of the multiplexed light after transmission has a first light intensity at a first wavelength, a second light intensity at a second wavelength, and a third light intensity at a third wavelength. The spectrum of the halogen lamp light has a fourth light intensity at the first wavelength, a fifth light intensity at the second wavelength, and a sixth light intensity at the third wavelength. Note that each of the wavelengths and light intensities used in the drawing is an example only for description.
[0065] When a ratio (first ratio) of the second light intensity to the first light intensity and a ratio (second ratio) of the fifth light intensity to the fourth light intensity match each other or a difference between the first ratio and the second ratio falls within an allowable range, both the spectra can be regarded as being similar in the wavelength range from the first wavelength to the second wavelength.
[0066] Similarly, when a ratio (third ratio) of the third light intensity to the second light intensity and a ratio (fourth ratio) of the sixth light intensity to the fifth light intensity match each other or a difference between the third ratio and the fourth ratio falls within an allowable range, both the spectra can be regarded as being similar in the wavelength range from the second wavelength to the third wavelength. This allowable range is desirably set to be the same as the allowable range in the difference between the first ratio and the second ratio. This is because light intensity ratios between wavelengths are desirably identical between spectra regardless of the magnitudes of the light intensities.
[0067] For convenience of description,
Second Embodiment: Summary
[0068] The automatic analyzer 10 according to the second embodiment is configured such that the range 502B encompasses the range 501A on the light receiving surface 302A by diffusing the light emitted from the second LED 502. As a result, the in-plane distribution of the light intensity of each LED can be made uniform on the light receiving surface 302A.
[0069] In the automatic analyzer 10 according to the second embodiment, the dichroic filter 506 is configured such that a light intensity ratio between wavelengths on the spectrum of the multiplexed light matches a light intensity ratio between the same wavelengths on the spectrum of the halogen lamp (or a difference between the light intensity ratios at the same wavelength falls within an allowable range). As a result, the spectrum of the multiplexed light after transmission becomes similar to the spectrum of the halogen lamp, so that even when LED light sources are used, characteristics can be obtained which are close to the analysis performance when the halogen lamp is used.
Third Embodiment
[0070] In order to stably obtain the analysis performance in the absorption analysis using the automatic analyzer 10, it is preferable that the light intensity of the light source unit 301 is always constant. As a means to keep the light intensity constant, temperature control of the LED mounting substrate 503 and drive current control of an LED can be used. Therefore, in a third embodiment of the present disclosure, a control procedure for stabilizing the light intensity of an automatic analyzer 10 will be described. The configuration of the automatic analyzer 10 is similar to that of each of the first and second embodiments.
[0071] For example, an AlGaN crystal that is a compound semiconductor is used as an LED that generates ultraviolet light having a wavelength of 340 nm or less. When the AlGaN crystal is used as a light emitting layer, the luminous efficiency of an ultraviolet LED is as low as from a few tenth to a few hundredth, as compared with the luminous efficiency of an InGaN crystal used fora light emitting layer of a general white LED. The light emitting layer of the AlGaN crystal has a feature that most of the input power becomes heat. The higher the operating temperature of an LED and the longer the operating time thereof, the more defects are formed in a semiconductor crystal, so that the light intensity decreases over time. Therefore, the life of an LED using an AlGaN crystal tends to be shorter than that of an LED using an InGaN crystal. In a commercially available LED, the specification value of the time L70 when the light intensity decreases to 70% is usually determined when the LED is used under a condition in which the lower surface temperature of a package is 25° C. In the case of an LED that generates ultraviolet light having a wavelength of 340 nm or less, L70 is 10,000 hours or longer, but it is known that L70 is shortened according to the Arrhenius model as the operating temperature rises. That is, when the LED is used at a lowered temperature, the light intensity can be increased, and the life can also be extended. The light intensity of the LED can also be increased by increasing a drive current.
[0072]
[0073]
[0074] For example, when the temperature of the LED mounting substrate 503 is PID controlled by a Peltier element, the PID parameter is determined based on the temperature data in the adjustment process of S702. When the environmental temperature is set to 25° C. and a temperature target value is set to 37° C., it takes time to stabilize the temperature if the temperature target is set to 37° C. Therefore, when the temperature data changes over time are gentle (i.e., it is likely to take time to stabilize the light intensity), the temperature target value is set to be higher than the original target value (e.g., set to be 42° C.). This makes it possible to quickly reach the target temperature. That is, the time until the light intensity becomes stable can be shortened by dynamically changing the target temperature according to the temperature changes over time.
Modifications of the Present Disclosure
[0075] The present disclosure is not limited to the embodiments described above, and includes various modifications. The above examples have been described in detail, for example, for easy understanding of the present disclosure, and they are not necessarily limited to those including all the configurations described above. In addition, a part of the configuration of an embodiment can be replaced with the configuration of another embodiment, or the configuration of an embodiment can be added with the configuration of another embodiment. In addition, a part of the configuration of each embodiment can be added or replaced with another configuration, or deleted.
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REFERENCE SIGNS LIST
[0077] 101: sample [0078] 102: sample cup [0079] 103: sample disk [0080] 104: reagent [0081] 105: reagent bottle [0082] 106: reagent disk [0083] 107: reaction solution [0084] 108: reaction cell [0085] 109: reaction disk [0086] 110: sample dispensing mechanism [0087] 111: reagent dispensing mechanism [0088] 112: agitating unit [0089] 113: absorbance measurement unit [0090] 114: cleaning unit [0091] 115: constant temperature fluid [0092] 201: control circuit [0093] 202: light intensity measurement circuit [0094] 203: data processing unit [0095] 2031: information recording unit [0096] 2032: analysis unit [0097] 204: input unit [0098] 205: output unit [0099] 301: light source unit [0100] 302: spectroscope [0101] 3021: diffraction grating [0102] 3022: detector array [0103] 401: optical axis [0104] 402: light source side slit [0105] 403: condensing lens [0106] 404: spectrometer side slit [0107] 501: first LED [0108] 502: second LED [0109] 503: LED mounting substrate [0110] 504: temperature adjustment unit [0111] 505: temperature sensor [0112] 506: dichroic filter [0113] 507: reflector [0114] 508: diffusion plate