Biological sample analyzer and biological sample analysis method
The biological sample analysis device addresses the issue of static-induced measurement errors by incorporating a static eliminator, enabling accurate luminescence intensity measurements and enhancing the reliability of microbial testing.
Patent Information
- Application Number
- JP2021530006
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2019-07-02
- Filing Date
- 2020-06-29
- Publication Date
- 2025-04-02
- Estimated Expiration
- 2040-06-29
AI Technical Summary
Existing biological sample analyzers face challenges in accurately measuring the intensity of luminescence from biologically derived substances due to container charging from static electricity, leading to measurement errors.
A biological sample analysis device equipped with a holder for multiple containers, a photodetector, a holder driving mechanism, and a static eliminator that removes static charges from the containers, ensuring accurate measurement of luminescence intensity.
The device effectively prevents measurement errors caused by static electricity, allowing for accurate detection of weak luminescence intensities and improving the reliability of microbial testing.
Smart Images

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Abstract
Description
[Technical field]
[0001] The present invention relates to a biological sample analyzer that analyzes light generated by a biological substance contained in a sample. [Background technology]
[0002] Conventionally, microbial monitoring has been carried out for the environmental management of pharmaceutical manufacturing plants, food plants, etc. As an example of this microbial monitoring, a luminescent reagent is added to ATP (adenosine triphosphate) contained in the microorganism, the bioluminescence is measured, and the obtained luminescence intensity is converted into an ATP value, which can be correlated with the bacteria.
[0003] One possible device for analyzing light generated by biological substances such as ATP is shown in Patent Document 1. This biological sample analyzer comprises a holder for holding a single container containing a sample, and a light-shielding box containing a photodetector, and is configured to detect light emitted from the sample in the container by placing the holder in the light-shielding box.
[0004] However, since the luminescence intensity of bioluminescence is an extremely small value, it needs to be measured by a highly sensitive photodetector such as a photomultiplier tube (PMT). Therefore, if the container in which the sample is stored is charged due to friction or other reasons, the light caused by the discharge of static electricity may be detected by the photodetector, resulting in a measurement error. [Prior art documents] [Patent documents]
[0005] [Patent Document 1] JP 2008-268019 A Summary of the Invention [Problem to be solved by the invention]
[0006] The present invention has been made in consideration of the problems described above, and aims to provide a biological sample analyzer that can prevent containers holding samples from becoming electrically charged and can accurately measure only the luminescence intensity of the luminescence from the sample. [Means for solving the problem]
[0007] The biological sample analyzer of the present invention is a biological sample analyzer for rapid microbial testing that analyzes light generated by biological substances contained in a sample, and is characterized in that it comprises a holder that holds a plurality of containers that accommodate the samples, a photodetector fixed at a predetermined position, a holder driving mechanism that drives the holder and sequentially positions each container held in the holder to a detection position by the photodetector, and a static eliminator that eliminates static electricity from the containers held in the holder.
[0008] In addition, the biological sample analysis method of the present invention is a biological sample analysis method using a biological sample analysis device for rapid microbial testing that analyzes light generated by biological substances contained in a sample, wherein the biological sample analysis device comprises a holder that holds a plurality of containers that accommodate the samples, a photodetector fixed at a predetermined position, and a holder driving mechanism that drives the holder and sequentially positions each container held in the holder at a detection position by the photodetector, and is characterized in that the containers held in the holder are de-ionized.
[0009] In this way, even if the container becomes charged for some reason, the static eliminator can eliminate the static electricity, and it is possible to prevent the container from becoming charged and generating a discharge due to static electricity, thereby preventing the light caused by the discharge from being detected by the photodetector. Therefore, it becomes possible for the photodetector to detect only the light generated by the biological substance in the container.
[0010] In addition, by removing the charge from the container, droplets of the sample are less likely to adhere to the wall surface of the container, reducing the amount of the sample that does not react with the reagent and preventing measurement errors.
[0011] In order to make it difficult for the effect of the neutralization action of the static eliminator on the container to be noticeable on the photodetector, the holder is configured to be rotatable about a predetermined center of rotation and holds the multiple containers on the same circumference about the center of rotation, and the static eliminator is positioned a predetermined arc length away from the photodetector in the circumferential direction in which the multiple containers are arranged.
[0012] As a specific embodiment of the static eliminator, there is mentioned one that supplies positive ions and negative ions to the container.
[0013] In order to sufficiently neutralize the portion of the container adjacent to the photodetector and prevent any effects of static electricity, the container may be configured to be roughly cylindrical with its tip exposed downward from the holder, and the static eliminator may be configured to supply positive ions and negative ions from below the container.
[0014] In order to prevent the holder itself from becoming charged and light due to discharge being detected by the photodetector, which would cause measurement errors, the holder may be made of a conductor.
[0015] In order to allow the electric charge built up on the container or the holder to escape to the outside, the holder only needs to be electrically connected to the holder drive mechanism and to earth.
[0016] A specific example of a configuration for dissipating the electric charge on the container or the holder to the earth is one in which the holder drive mechanism includes a rotating shaft connected to the holder and further includes an earth member that holds the side of the rotating shaft. In this case, even if wear occurs between the rotating shaft and the earth member, the elasticity of the earth member makes it easy to maintain contact.
[0017] In order to prevent the container from being charged through the transfer of the sample due to the electric charge being generated by a member related to a process before the sample is contained in the container, the device further includes a dispensing mechanism for introducing a reagent that reacts with the biological substance to generate light into the container, the dispensing mechanism is configured to be detachable from a pipette tip that comes into contact with the reagent, and the pipette tip is wet before use. In this way, the pipette tip can be made difficult to be charged, and the container can be prevented from being charged through the transfer of the sample.
[0018] In order to block light from entering the detector from the outside when the light detector detects the light emitted from the sample, while preventing the light-blocking components from becoming charged and causing measurement errors, the container may further include a light-blocking mechanism that is provided on the container and includes a container-side light-blocking part that covers an upper part of the container, and a movable-side light-blocking part that moves toward and away from the container at the detection position and covers a lower part of the container at the detection position, and each of the container-side light-blocking part and the movable-side light-blocking part may be formed of metal.
[0019] In order to facilitate cleaning operations etc. to prevent light emission from the sample from being blocked when water droplets accumulate inside the light-shielding mechanism, the movable light-shielding part needs to include a reflector body covering the tip side of the container, a light-transmitting plate provided within the reflector body, and a pressing member that is detachable from the reflector body and presses and fixes the light-transmitting plate against the reflector body.
[0020] In order to prevent the pressing member from absorbing the luminescence from the sample and causing measurement errors, it is sufficient that the pressing member is roughly ring-shaped and attached inside the reflector body, and that a reflective film is provided on its inner surface.
[0021] In order to accurately control the temperature to keep the state of the sample constant before measurement and to reduce errors in the installation position of the thermistor, it is sufficient to further include a temperature control mechanism comprising: a holder block that holds a specimen tube containing the sample before it is dispensed into the container; a heat source unit provided in the holder block; a thermistor that has a temperature sensor and a lead wire connected to the temperature sensor and measures the temperature of the holder block; a storage hole formed in the holder block for storing the thermistor therein; and an insert that covers the lead wire of the thermistor and is inserted into the storage hole, and the base end side of the insert is formed with an abutment surface that abuts against the opening periphery of the storage hole. Effect of the Invention
[0022] In this way, with the biological sample analyzer of the present invention, the container is neutralized by the static eliminator, preventing the container from becoming charged and preventing light due to electrostatic discharge from being detected by the photodetector. Therefore, since only the light from the sample can be measured, even if the luminescence intensity is very weak, it can be measured accurately. [Brief description of the drawings]
[0023] [Figure 1] 1 is a schematic diagram showing the configuration of a biological sample analyzer according to an embodiment of the present invention. [Diagram 2] FIG. 2 is a perspective view showing the external appearance of the biological sample analyzer of the same embodiment. [Diagram 3] FIG. 2 is a plan view showing the arrangement of each part of the device main body of the embodiment. [Figure 4] FIG. 2 is a schematic cross-sectional view showing the internal structure of the temperature adjustment mechanism of the embodiment. [Diagram 5] FIG. 2 is a perspective view showing a holder holding a plurality of containers according to the embodiment. [Figure 6] 5A and 5B are schematic diagrams showing the positions of the movable light blocking portion of the light blocking mechanism and the surrounding structure of the embodiment. [Figure 7] FIG. 2 is a schematic perspective view showing a structure of the earth member of the embodiment. [Figure 8]FIG. 4 is a schematic exploded cross-sectional view showing the structure of a movable-side light shielding portion of the embodiment. [Explanation of symbols]
[0024] 100 Biological sample analyzer Xdet...detection position 2...container 3 Holder 4. Photodetector NE...Static eliminator 5. Holder drive mechanism 6 Dispensing mechanism 11 Reflector 13...shading mechanism 131... Container side light shielding portion 132...Movable side light shielding part DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0025] An embodiment of a biological sample analyzer according to the present invention will now be described with reference to the drawings.
[0026] <Device configuration> The biological sample analyzer 100 for rapid microorganism testing of this embodiment measures the amount of a biological substance contained in a sample by analyzing light generated by the biological substance. In other words, the biological sample analyzer 100 of this embodiment is a biological sample analyzer for highly sensitive microorganism testing, and is intended for measurements where the photon count is, for example, 1000 counts per second or less. In this embodiment, the zero point is set to 30 to 100 counts per second, and measurements are intended where a difference of a few counts corresponds to the amount of one bacterium present. Note that, hereinafter, the amount of ATP (adenosine triphosphate) (amol (=10 -18 This article describes an ATP amount measuring device that measures ATP (100 mol) by detecting weak light emitted from ATP.
[0027] Specifically, as shown in FIG. 1, this biological sample analysis device 100 comprises a holder 3 that holds multiple containers 2 for containing samples, a photodetector 4 fixed in a predetermined position, a holder driving mechanism 5 that moves the holder 3, and a dispensing mechanism 6 that dispenses a luminescent reagent that reacts with ATP to produce light into the containers 2 held by the holder 3.
[0028] As shown in Figs. 2 and 3, the biological sample analyzer 100 of this embodiment includes an apparatus main body 101 placed on a table such as a clean bench, and a cover body 102 provided on the apparatus main body 101. The apparatus main body 101 is provided with measurement equipment necessary for ATP measurement, such as a holder 3, a holder drive mechanism 5, and a dispensing mechanism 6. The apparatus main body 101 also has an opening 101H on the front side. The cover body 102 is provided so as to be openable and closable relative to the opening 101H of the apparatus main body 101. Specifically, the opening 101H is openable and closable by a horizontal connecting shaft (not shown) at the upper part thereof, and the user can access the inside of the apparatus main body 101 by lifting the cover body 102 upward. When the cover body 102 is closed, the gap between the cover body 102 and the opening 101H is sealed by a sealing member (not shown), so that the inside of the apparatus is in a darkroom state.
[0029] In addition, the device main body 101 is provided with a temperature control mechanism 7 that holds and controls the temperature of multiple sample tubes FC containing samples, a reagent setting section 8 in which reagent containers RC1 and RC2 containing each reagent are set, and a pipette tip setting section 9 in which pipette tips PT used in the dispensing mechanism 6 are provided.
[0030] The temperature adjustment mechanism 7 accommodates and holds a plurality of specimen tubes FC, for example, in a matrix. The temperature adjustment mechanism 7 includes a metal (for example, aluminum) holder block 71 that holds the specimen tubes FC, a heater 72 and the like that are heat sources provided in the holder block 71, and a thermistor 73 that detects the temperature of the holder block 71. Based on the detected temperature of the thermistor 73, the heater 72 that is the heat source is controlled by the control device COM so that the temperature of the holder block 71 becomes a predetermined temperature. As shown in FIG. 4, the holder block 71 is formed with an insertion hole 711 that is roughly two-stage cylindrical for inserting the thermistor 73 therein, and a temperature sensor 731 at the tip of the thermistor 73 is arranged all the way into the insertion hole 711. Specifically, two lead wires connected to the temperature sensing element 731 of thermistor 73 are inserted into insert 74, which has a disk-shaped base end with a thin cylinder protruding from the center, and temperature sensing element 731 is exposed from the tip of insert 74. In this state, insert 74 is inserted into insertion hole 711, and the abutting surface of the disk-shaped portion of insert 74 is brought into abutment with the periphery of the opening of insertion hole 711. In this manner, the position of temperature sensing element 731 of thermistor 73 can always be positioned in the same position even if insertion hole 711 is formed deep. Furthermore, insert 74 is fixed in insertion hole 711 by a sealing material such as resin.
[0031] A reagent container RC1 containing a pretreatment reagent for pretreatment of a specimen and a reagent container RC2 containing a luminescence reagent are set in the reagent setting section 8. The pretreatment reagent includes an ATP elimination solution for eliminating ATP (free ATP) other than that of living cells (living bacteria) contained in the specimen, and an ATP extraction solution for extracting ATP from living cells.
[0032] The holder 3 is provided rotatably with respect to the device body 101, and as shown in FIG. 5, the holder 3 holds a plurality of containers 2 on the same circumference with respect to a predetermined center of rotation. In addition to the plurality of containers 2 for sample measurement, the holder 3 of this embodiment also holds a container 2b for blank measurement and a container 2s for standard solution measurement. In addition, inside the plurality of containers 2 in the holder 3, a waste box 10, which is a waste tip storage section for disposing of the pipette tips PT of the dispensing mechanism 6, is integrally provided. The waste box 10 has an opening 10x that is arc-shaped in a plan view. Furthermore, the holder 3 is configured to be detachable from the device body 101, and in order to facilitate this attachment and detachment operation, a plurality of (here, two) holding holes 3h for holding are formed. The holding holes 3h are through holes for inserting and holding fingers, and are provided inside the opening 10x of the waste box 10. Since the holding holes 3h are provided inside the opening 10x in this way, it is possible to prevent hands from accidentally touching the discarded pipette tips PT when holding the holder 3. In this embodiment, the holder 3 is made of metal and is configured not to become electrically charged due to friction or the like when a finger is inserted.
[0033] As shown in FIG. 1, the photodetector 4 detects light emitted from a sample in a container 2 held by a holder 3, and in this embodiment, it is, for example, a photomultiplier tube (PMT). The photodetector 4 is provided below the container 2 held by the holder 3. An optical system 12 having a reflector 11 for guiding light emitted from the sample in the container 2 to the photodetector 4 is provided above the photodetector 4. The reflector 11 is configured to be movable toward and away from the container 2 located above them. By bringing the reflector 11 close to the container 2, light emitted from the sample in the container 2 can be efficiently guided to the photodetector 4, and by retracting the reflector 11 from the container 2, it is possible not to interfere with the movement of the container 2. In this embodiment, the other optical system 12 including the reflector 11 and the photodetector 4 are configured to be movable toward and away from the container 2.
[0034] In this embodiment, as shown in FIG. 1, not only the photodetector 4 but also a static eliminator NE for eliminating static electricity from the container 2 is provided below the holder 3. The static eliminator NE eliminates static electricity from the container 2 by supplying negative ions and positive ions from the underside of the container 2. In this way, the static eliminator NE supplies both negative ions and positive ions, so that the container 2 can be reliably eliminated regardless of whether it is positively or negatively charged. The timing for supplying the negative ions and positive ions may be the same or different. In this way, the biological sample analyzer 100 can prevent the occurrence of a discharge phenomenon due to static electricity by reliably eliminating the static electricity from the container 2. Therefore, the biological sample analyzer 100 can prevent measurement errors from occurring due to the detection of light due to a discharge phenomenon.
[0035] This static eliminator NE is provided at a distance from the photodetector 4 by a predetermined arc length in the circumferential direction, which is the arrangement direction of the containers 2. In this embodiment, the static eliminator NE is disposed on the opposite side of the photodetector 4 with respect to the center of rotation of the holder 3. That is, the static eliminator NE is disposed at a position furthest from the photodetector 4 on the circumference on which the containers 2 are arranged. In this embodiment, after each container 2 is neutralized by the static eliminator NE, the holder 3 rotates and is positioned at the detection position Xdet. This configuration makes it possible to neutralize the containers 2 while preventing ions supplied from the static eliminator NE from being detected by the photodetector 4.
[0036] The holder driving mechanism 5 moves the holder 3 and sequentially positions each container 2 held in the holder 3 at a detection position Xdet by the photodetector 4. Specifically, as shown in FIG. 1, the holder driving mechanism 5 includes an installation table 51 on which the holder 3 is installed, a rotation shaft 52 for rotating the holder 3 installed on the installation table 51, and an actuator 53 for rotating the rotation shaft 52. In addition, the holder driving mechanism 5 is provided with a rotation position sensor (not shown) for detecting the rotation position of the holder 3. Based on a detection signal from this rotation position sensor, the actuator 53 is rotationally controlled by the control device COM so as to position the container 2 to be measured at the detection position Xdet.
[0037] In this embodiment, the holder 3 is electrically connected to the rotating shaft 52 via the installation base 51. Therefore, the installation base 51 and the rotating shaft 52 are made of metal. As shown in Figs. 6 and 7, the charge of the holder 3 is connected to the ground by the ground member GR attached to the rotating shaft 52. More specifically, the ground member GR is a three-claw leaf spring member that holds the side of the rotating shaft 52. Each of the claws that are provided to sandwich the rotating shaft 52 is biased so as to press inward. In this way, each of the claws is in line contact with the rotating shaft 52 and is biased inward, so that even if wear occurs between the rotating shaft 52 and the ground member GR, the state of line contact can be almost maintained, and the charge accumulated in the holder 3 can continue to flow to the ground.
[0038] As shown in Figures 1 to 3, the dispensing mechanism 6 includes a nozzle 61 for aspirating or discharging a sample or each reagent, a pump mechanism 62 such as a syringe that drives the aspirating or discharging of the nozzle 61 via a flow path connected to the nozzle 61, and a nozzle moving mechanism 63 that moves the nozzle 61 in a predetermined direction.
[0039] The nozzle 61 is equipped with a tip holder 611 that detachably holds a pipette tip PT for contacting and holding a sample or each reagent. The tip holder 611 has an internal flow path formed therein, the flow path is connected to its base end, and the pipette tip PT is connected to its tip opening. The pipette tip PT is kept wet in the tip holder 611.
[0040] Further, the nozzle moving mechanism 63 linearly moves the nozzle 61 in the horizontal direction (X-axis direction and Y-axis direction) and also linearly moves the nozzle 61 in the vertical direction (Z-axis direction). Specifically, the nozzle moving mechanism 63 includes a movable member 631 that holds the nozzle 61, slide mechanisms 632 that are provided in the X-axis direction, Y-axis direction, and Z-axis direction, respectively, and an actuator 633 that moves the movable member 631 in each direction along the slide mechanism 632. The actuator 633 and the pump mechanism 62 are controlled by the control device COM to perform each operation in the ATP measurement.
[0041] As shown in FIG. 6, the biological sample analyzer 100 of this embodiment is equipped with a light-shielding mechanism 13 that guides light emitted from a sample in a container 2 at the detection position Xdet to the photodetector 4, while preventing light emitted from samples in other containers 2 (specifically, containers 2 where measurement has been completed) from being guided to the photodetector 4.
[0042] The light blocking mechanism 13 includes a container-side light blocking part 131 provided in each container 2, and a movable-side light blocking part 132 that moves toward and away from the container 2 located at the detection position Xdet.
[0043] The container-side light-shielding portion 131 is made of a material that does not have optical transparency, and covers the upper part of each container 2. Specifically, the container-side light-shielding portion 131 covers the entire periphery of the upper part of each container 2. In this embodiment, a cylindrical container-side light-shielding portion 131 is provided in the container holding portion of the holder 3, and the container 2 is accommodated in the container-side light-shielding portion 131, so that the container-side light-shielding portion 131 covers the entire periphery of the upper part of the container 2 held by the holder 3.
[0044] The movable side light shielding part 132 is made of a material that does not have optical transparency and covers the lower part of the container 2 at the detection position Xdet except for the upper part covered by the container side light shielding part 131. Specifically, the movable side light shielding part 132 covers the entire circumference of the lower part of the container 2 at the detection position Xdet. This movable side light shielding part 132 moves up and down between a light shielding position S that covers the lower part of the container 2 at the detection position Xdet and a retracted position T that is spaced downward from the lower part of the container 2. The movable side light shielding part 132 moves up and down by a lifting device 14 that uses an actuator, for example. This lifting device 14 is controlled by the control device COM in conjunction with the operation of the holder driving mechanism 5 and the dispensing mechanism 6.
[0045] A first step 131a is formed around the entire circumference at the lower end of the container side light shielding part 131, and a second step 132A corresponding to the first step 131a is formed around the entire circumference at the upper end of the movable side light shielding part 132. When the movable side light shielding part 132 is in the light shielding position S, the first step 131a of the container side light shielding part 131 and the second step 132A of the movable side light shielding part 132 engage with each other to cover both the upper and lower parts of the container 2 at the detection position Xdet. The engagement of the first step 131a and the second step 132A in this manner ensures light shielding. Either one of the steps 131a or 132A may be groove-shaped.
[0046] When the dispensing mechanism 6 introduces the luminescent reagent into the sample in the container 2, the movable side light-shielding portion 132 is in the light-shielding position S, and when the luminescence measurement is completed and the container 2 at the detection position Xdet is switched, the movable side light-shielding portion 132 is in the retracted position T.
[0047] Moreover, the movable-side light shielding portion 132 in this embodiment constitutes the reflector 11 that guides the light emitted from the sample in the container 2 located at the detection position Xdet to the photodetector 4.
[0048] More specifically, as shown in Figures 6 and 8, the movable-side light-shielding portion 132 includes a reflector body 132a that covers the tip side of the container 2, a glass plate that is a light-transmitting plate 132b provided in the reflector body 132a, and a pressing member 132c that is detachable from the reflector body 132a and presses and fixes the light-transmitting plate 132b to the reflector body 132a.
[0049] The reflector body 132a is a cylindrical body having a tapered inner circumferential surface, for example, mirror-finished, which gradually widens from the upper opening downward. A step is formed on the tip side of the reflector body 132a, and the light-transmitting plate 132b is pressed against this step. A female thread is formed on the tip side of the reflector body 132a.
[0050] The light-transmitting plate 132b is substantially disc-shaped and has an outer diameter substantially equal to the inner diameter of the tip of the reflector body 132a. The pressing member 132c is substantially ring-shaped and has a male thread on its outer circumferential surface that is threaded with a female thread formed on the tip of the reflector body 132a. The inner circumferential surface of the pressing member 132c is provided with a reflective film so that the light that has passed through the light-transmitting plate and has reached the inner circumferential surface of the pressing member is also guided to the photodetector 4. Since the movable-side light-shielding part 132 is configured such that the light-transmitting plate 132b can be detached from the reflector body 132a, for example, even if water droplets or dirt adhere to the light-transmitting plate 132b, it can be easily cleaned and maintained. Furthermore, since the inner circumferential surface of the pressing member 132c is provided with a reflective film, it is possible to prevent the light generated by the sample from being lost in this portion.
[0051] In this way, a reflector 11 facing the photodetector 4 is formed on the inner surface of the movable-side light-shielding portion 132. This reflector 11 makes it possible to guide the light emitted from the side wall of the container 2 at the detection position Xdet to the photodetector 4 without leaking.
[0052] <Analysis method>
[0053] Next, the operation and analysis method of the biological sample analyzer 100 configured as described above will be explained.
[0054] For example, a large volume (e.g., 50 ml to 200 ml) of specimen is concentrated to a predetermined volume (e.g., 1 μl to 1000 μl) to generate a sample. The specimen tube FC containing this sample is set in the temperature control mechanism 7 of the device main body 101. The holder block 71 of the temperature control mechanism 7 is controlled to a constant temperature by the heater 72. With a predetermined number of specimen tubes FC set, the cover body 102 is closed and measurement is started. Note that in this state, each container 2 held in the holder 3 is empty, but the container 2 for standard solution measurement contains a standard solution with a known amount of ATP.
[0055] When the measurement is started, the control device COM controls the dispensing mechanism 6 to dispense each pretreatment reagent into each of the sample tubes FC held by the temperature control mechanism 7 according to a predetermined sequence. This causes the samples in the sample tubes FC to undergo a predetermined pretreatment (ATP extraction). After that, the dispensing mechanism 6 introduces the pretreated samples in each of the sample tubes FC into each of the containers 2 held by the holder 3.
[0056] Then, the control device COM controls the holder drive mechanism 5 to move the container 2 to be measured to the detection position Xdet. In this process, ions are supplied to the container 2 passing over the static eliminator NE, and static electricity is removed from the container 2. After moving the container 2 to be measured to the detection position Xdet, the control device COM controls the lifting device 14 to move the movable side light shielding part 132 of the light shielding mechanism 13 to the light shielding position S. After this state is achieved, the control device COM controls the dispensing mechanism 6 to introduce the luminescent reagent into the container 2 at the detection position Xdet. As a result, the light emitted from the sample in the container 2 at the detection position Xdet is detected by the photodetector 4. The light intensity signal obtained by the photodetector 4 is subjected to arithmetic processing by the control device COM to calculate the amount of ATP (amol). Of the light intensity signals obtained by the photodetector 4, the signal used for arithmetic processing is an integrated signal from the time when the luminescent reagent is introduced until a predetermined time (for example, several seconds).
[0057] After the emission measurement of one container 2 is completed, the control device COM controls the lifting device 14 to move the movable light-shielding part 132 of the light-shielding mechanism 13 to the retracted position T, and then controls the holder driving mechanism 5 to move the next container 2 to be measured to the detection position Xdet. In this manner, the emission measurement of the sample in each container 2 is performed in sequence. Before the emission measurement of each container 2, a blank measurement and a standard solution measurement are performed, and zero-point calibration and span calibration are performed.
[0058] After all samples have been measured in this manner, the cover body 102 is opened to replace the specimen tubes FC held by the temperature control mechanism 7, and the containers 2 held by the holder 3 are replaced. When replacing the containers 2 held by the holder 3, the holder 3 is removed from the device body 101 by holding the holding holes 3h of the holder 3. Since the used and discarded pipette tips PT are stored in the disposal box 10 of the holder 3 in the holder 3, by removing the holder 3 from the device body 101, the discarded pipette tips PT can also be taken out of the device body 101 at the same time.
[0059] <Effects of this embodiment>
[0060] According to biological sample analyzer 100 of this embodiment configured as described above, the container 2 is neutralized by the static eliminator NE, which prevents measurement errors caused by the container 2 becoming charged and causing a discharge due to static electricity, which then causes the discharge light to be detected by the photodetector 4. Furthermore, because the container 2 has been neutralized, it is possible to prevent a situation in which part of the sample is attracted by static electricity and adheres to the inner wall surface of the container 2 as droplets, resulting in part of the sample not reacting with the reagent.
[0061] As a result, even a very small luminescence intensity can be detected, and the accuracy of calculating the amount of ATP (amol) can be improved compared to conventional methods.
[0062] The dispensing mechanism 6 introduces a reagent into the container 2 at the detection position Xdet, so that light can be detected without omission from the time when light emission starts. Here, before the dispensing mechanism 6 introduces the reagent, light emitted from the samples in the containers 2 other than the container 2 at the detection position Xdet is blocked by the light blocking mechanism 13, so that light can be detected with high accuracy from the time when light emission starts.
[0063] Since the light shielding mechanism 13 is divided into a container-side light shielding part 131 fixed to the container 2 side and a movable-side light shielding part 132 movable relative to the container 2, there is no need to cover the entire container 2 with movable members. As a result, the movable members of the light shielding mechanism 13 can be configured compactly and the configuration can be simplified.
[0064] And, since the movable-side light-shielding part 132 constitutes the reflector 11 that guides the light emitted from the sample in the container 2 at the detection position Xdet to the photodetector 4, the light emitted from the sample can be efficiently guided to the photodetector 4. Here, since a reflective film is also provided on the pressing member 132c located on the tip side of the light-transmitting plate 132b, the loss of the light emitted from the sample can be further reduced.
[0065] Since the light-shielding mechanism 13 covers the entire circumference of the container 2 at the detection position Xdet, it not only blocks as much light as possible from containers 2 other than the container 2 at the detection position Xdet, but also blocks other stray light, thereby further reducing noise.
[0066] <Other embodiments>
[0067] The present invention is not limited to the above-described embodiment.
[0068] For example, the holder 3 holds a plurality of containers 2 on the same circle, but may hold them along a predetermined direction, such as in a matrix. In this case, the holder drive mechanism 5 may be configured to move the holder 3 linearly in the horizontal direction (X-axis direction and Y-axis direction).
[0069] In this case, the static eliminator NE may be configured to supply ions onto the movement path of the container 2. In addition, the static eliminator NE is not limited to one that supplies ions from the bottom side of the container 2, and may be configured to supply ions from, for example, the side surface of the container 2 to perform static elimination.
[0070] The biological sample analyzer 100 for rapid microorganism testing according to the present invention is not limited to an ATP amount measuring device as shown in the embodiment. Specific examples of rapid microorganism testing include bioluminescence and fluorescence methods that measure ATP and the like, immunological methods that measure antigens, and solid-phase cytometry and flow cytometry that measure bacteria. The biological sample analyzer 100 for rapid microorganism testing according to the present invention can also measure mycoplasma and endotoxin.
[0071] In addition, various modifications and combinations of parts of each embodiment may be made as long as they do not go against the spirit of the present invention. [Industrial Applicability]
[0072] The present invention can provide a biological sample analyzer that can prevent a container that holds a sample from becoming electrically charged and can accurately measure only the luminescence intensity of luminescence from the sample.
Claims
1. A biological sample analyzer for rapid microbial testing that analyzes light generated by a biological substance contained in a sample, comprising: a holder for holding a plurality of containers for accommodating the samples; a photodetector disposed below the container and fixed in place; a holder driving mechanism that drives the holder to sequentially position each container held by the holder at a detection position by the photodetector; a static eliminator disposed below the container and configured to eliminate static electricity from the container held by the holder, In the same holder, the static eliminator supplies positive ions and negative ions from below the container to eliminate static electricity from the container, and the photodetector detects light emitted from the sample in the container; the holder is configured to be rotatable about a predetermined rotation center and holds the plurality of containers on the same circumference about the rotation center, The static eliminator is disposed on the opposite side of the photodetector from the center of rotation of the holder in the circumferential direction of the holder in which the multiple containers are arranged.
2. The biological sample analyzer according to claim 1 , wherein the static eliminator supplies positive ions and negative ions to the container.
3. 3. The biological sample analyzer according to claim 2, wherein the container is generally cylindrical and has a tip portion exposed downward from the holder.
4. 4. The biological sample analyzer according to claim 1, wherein the holder is made of a conductive material.
5. 5. The biological sample analyzer according to claim 1, wherein the holder is electrically connected to the holder drive mechanism and to a ground.
6. the holder drive mechanism includes a rotation shaft connected to the holder; 6. The biological sample analyzer according to claim 1, further comprising an earth member that holds a side surface of the rotating shaft.
7. A dispensing mechanism for introducing a reagent into the container that reacts with the biological substance to generate light, The dispensing mechanism is configured to be detachable from a pipette tip that comes into contact with the reagent, 7. The biological sample analyzer according to claim 1, wherein the pipette tip is wet prior to use.
8. a light shielding mechanism provided on the container, the light shielding mechanism including a container-side light shielding part that covers an upper portion of the container, and a movable light shielding part that moves toward and away from the container at the detection position and covers a lower portion of the container at the detection position; 8. The biological sample analyzer according to claim 1, wherein the container side light shielding part and the movable side light shielding part are each made of metal.
9. The movable light shielding portion is A reflector body covering a tip side of the container; a light-transmitting plate provided in the reflector body; 9. The biological sample analyzer according to claim 8, further comprising a pressing member that is detachable from the reflector body and presses and fixes the light transmitting plate to the reflector body.
10. 10. The biological sample analyzer according to claim 9, wherein the pressing member is generally ring-shaped and is attached inside the reflector body, and a reflective film is provided on the inner peripheral surface of the pressing member.
11. a holder block for holding a sample tube containing the sample before it is dispensed into the container; a heat source provided in the holder block; a thermistor including a temperature sensor and a lead wire connected to the temperature sensor, for measuring the temperature of the holder block; a receiving hole formed in the holder block for receiving the thermistor therein; a temperature control mechanism including an insert that covers a lead wire of the thermistor and is inserted into the accommodation hole, 11. The biological sample analyzer according to claim 1, wherein a contact surface that contacts the periphery of the opening of the receiving hole is formed on the base end side of the insert.
12. A biological sample analysis method using a biological sample analyzer for rapid microbial testing that analyzes light generated by a biological substance contained in a sample, comprising: the biological sample analyzer comprises a holder that holds a plurality of containers that contain the samples, a photodetector that is disposed below the containers and fixed at a predetermined position, and a holder drive mechanism that drives the holder and sequentially positions each of the containers held in the holder at a detection position by the photodetector; the holder is configured to be rotatable about a predetermined rotation center and holds the plurality of containers on the same circumference about the rotation center, a static eliminator is disposed on an opposite side of the photodetector with respect to a rotation center of the holder in a circumferential direction of the holder in which the plurality of containers are arranged; A biological sample analysis method comprising the steps of: in the same holder, neutralizing the container held in the holder by supplying positive ions and negative ions from below the container; and detecting light emitted from the sample in the container by the photodetector.
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