Automatic analysis device and mass sensor

Abstract

[Problem] To accurately dispense a sample and a sample of a predetermined dispensed amount and ensure reliability of analysis results. The automatic analysis device is provided with: a reagent holding unit that holds a reagent container in which a reagent is accommodated; a specimen holding unit that holds a specimen container that accommodates a specimen; a dispensing mechanism that dispenses the reagent and the specimen into a reaction container (105); and a mass sensor (2) that measures the mass of the reaction vessel. The mass sensor (2) is provided with: a fixed part (204); a vibration plate (203), at least a part of which is fixed to the fixing part; a piezoelectric element (202) that is bonded to the vibration plate (203); and a container installation unit (205) which is supported by the vibration plate (203) and is configured so as to be able to install the reaction container (205) from which the liquid to be measured is discharged.

Description

Technical Field

[0001] The present invention relates to an automatic analyzing device and a mass sensor. Background Art

[0002] Clinically, the concentration of chemical substances such as proteins, lipids, sugars, ions, and various components constituting them contained in body fluids such as blood and urine is quantitatively measured. An automatic analyzer is known as a device for automating the steps required for the measurement (e.g., quantitative separation of specimen samples, mixing with reagents, determination of reaction results, measurement of changes in substances contained in reagents, etc.).

[0003] The automatic analyzer reacts a predetermined amount of sample with a reagent in a reaction container, measures the absorbance or luminescence of the sample, and thereby analyzes the components of the sample. The device is equipped with a dispensing mechanism for dispensing the sample and the reagent into the reaction container. The dispensing mechanism is required to be configured to dispense a predetermined amount of sample and reagent.

[0004] In an automatic analyzer, the mass of liquid dispensed in one dispensing operation is as small as about 4 to 60 mg. Therefore, it is difficult to accurately measure the mass of the dispensed liquid. If an abnormality occurs in the dispensing mechanism and the analysis is performed without obtaining the predetermined dispensing amount, the correct analysis result cannot be obtained.

[0005] In addition, the automatic analyzer has various motors and movable parts, including a dispensing mechanism, and therefore has a problem of many interferences caused by vibrations. In order to measure the accurate mass of the dispensed specimens and reagents without being affected by interfering vibrations, it is also considered to provide an anti-vibration table, on which an electronic balance is provided. However, the anti-vibration table is large in size, and therefore providing the anti-vibration table in the automatic analyzer will lead to the enlargement of the automatic analyzer, which is not realistic. In view of such a situation, in order to ensure the reliability of the analysis results, an automatic analyzer and a mass sensor are required that can accurately dispense specimens and samples to ensure the reliability of the analysis results.

[0006] Prior art literature

[0007] Patent Literature

[0008] Patent Document 1: Japanese Patent Application Publication No. 2010-217048 Summary of the invention

[0009] Problems to be solved by the invention

[0010] The present invention provides an automatic analyzer and a mass sensor capable of accurately dispensing a predetermined amount of a specimen and a sample to ensure the reliability of the analysis result.

[0011] Means for solving problems

[0012] The automatic analyzer of the present invention comprises: a reagent holding part that holds a reagent container containing a reagent; a specimen holding part that holds a specimen container containing a specimen; a dispensing mechanism that dispenses the reagent and the specimen into a reaction container; and a mass sensor that measures the mass of the reaction container. The mass sensor comprises: a fixing part; a vibration plate at least a part of which is fixed to the fixing part; a piezoelectric element that is joined to the vibration plate; and a container setting part that is supported on the vibration plate and is configured to be able to set the reaction container into which the liquid to be measured is discharged.

[0013] The mass sensor of the present invention measures the mass of liquid discharged into a reaction container, and comprises: a fixing portion; a vibration plate, at least a portion of which is fixed to the fixing portion; a piezoelectric element connected to the vibration plate; and a container setting portion, which is supported on the vibration plate and is configured to be able to set the reaction container for the discharged reagent and the specimen.

[0014] Effects of the Invention

[0015] According to the present invention, it is possible to provide an automatic analyzer and a mass sensor that can accurately dispense a predetermined amount of a specimen and a sample and ensure the reliability of the analysis result. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 It is an overall schematic diagram of the automatic analyzer 1 according to the first embodiment.

[0017] Figure 2 It is a perspective view showing a detailed structure of the mass sensor 2 .

[0018] Figure 3 : is a graph for explaining the operation of the mass sensor 2 .

[0019] Figure 4 This is a flowchart for explaining the operation of the automatic analyzer 1 according to the first embodiment.

[0020] Figure 5 This is a flowchart for explaining the operation of the automatic analyzer 1 according to the second embodiment. DETAILED DESCRIPTION

[0021] Hereinafter, the present embodiment will be described with reference to the accompanying drawings. In the accompanying drawings, functionally identical elements are sometimes shown with the same number or corresponding number. In addition, the accompanying drawings show implementations and installation examples that follow the principles of the present disclosure, but they are used to understand the present disclosure and are by no means used to interpret the present disclosure in a limiting manner. The descriptions in this specification are merely typical examples and do not limit the patent protection scope or application examples of the present disclosure in any sense.

[0022] In the present embodiment, the present disclosure is described in sufficient detail so that those skilled in the art can implement the present disclosure, but other installations and methods are also possible, and it is necessary to understand that the structure and construction can be changed and various elements can be replaced without departing from the scope and spirit of the technical idea of ​​the present disclosure. Therefore, the following description should not be interpreted as being limited to this.

[0023] [First embodiment]

[0024] Reference Figure 1 , the overall structure of the automatic analyzer 1 of the first embodiment is described. As an example, the automatic analyzer 1 is roughly composed of the following structures: a reagent disk (reagent holding part) 102, a specimen disk (specimen holding part) 104, an incubator 106, a reaction container tray 107, a clamp 108, a detection unit 109, a reaction container waste port 110, a dispensing mechanism 111, a mass sensor 2, and a cleaning tank 117.

[0025] The reagent disk 102 is a reagent holding unit for holding a reagent container 101 containing a reagent used in the analysis. The specimen disk 104 is a specimen holding unit for holding a specimen container 103 containing a specimen to be inspected. The reagent disk 102 and the specimen disk 104 are respectively configured to be movable (e.g., rotatable around a rotation axis) by moving mechanisms 102a and 104a. By moving the reagent disk 102 and the specimen disk 104, the dispensing mechanism 111 accesses the reagent container 101 and the specimen container 103, and can aspirate the reagent and the specimen (liquid). In addition, after aspiration, the dispensing mechanism 111 can access the reaction container 105 configured at the discharge position 112 of the mass sensor 2, and discharge the aspirated liquid.

[0026] The incubator 106 has the following functions: promoting the reaction of the reaction container 105 injected with the reagent and the specimen in an environment where the temperature is adjusted to a constant temperature. The reaction container tray 107 holds the unused reaction container 105. The clamp 108 has the following functions: grasping the reaction container 105 and transporting it to the mass sensor 2, the detection unit 109, the reaction container disposal port 110, etc. The detection unit 109 receives the reaction container 105 that has passed the predetermined reaction time in the incubator 106 and performs the analysis of the specimen. The reaction container disposal port 110 constitutes a disposal part for discarding the used reaction container 105 after the analysis is completed. The cleaning tank 117 can clean the dispensing mechanism 111. By cleaning, it is possible to prevent the residue of components when dispensing different liquids.

[0027] The mass sensor 2 is a measuring unit that measures the mass of the liquid discharged into the reaction container 105 disposed at the discharge position 112 . Figure 22 is a perspective view showing a detailed structure of the mass sensor 2. As an example, the mass sensor 2 includes a piezoelectric element 202, a vibration plate 203, a fixing portion 204, a container installation portion 205, and a control portion 206.

[0028] like Figure 2 As shown in the figure, as an example, the piezoelectric element 202 can be bonded to one or both surfaces of the vibration plate 203 at a position concentric with the vibration plate 203 formed in a circular plate shape. The piezoelectric element 202 is polarized in the thickness direction, and when an AC voltage is applied to the electrodes formed on both surfaces, the vibration plate 203 can generate a flexural vibration with the center position of the circular plate as an antinode through the expansion and contraction of the piezoelectric element 202. In addition, the vibration plate 203 can be made of a metal material such as aluminum or titanium.

[0029] The fixing part 204 constitutes the base part of the mass sensor 2, for example Figure 2 As shown, the upper fixing member and the lower fixing member are provided, and the vibration plate 203 can be fixed by sandwiching the outer peripheral portion of the vibration plate 203 from the upper and lower sides using the upper and lower fixing members. That is, the vibration plate 203 is configured so that vibration can be obtained with the fixing portion 204 as the fixed end. The outer peripheral portion of the vibration plate 203 does not need to be fixed to the fixing portion 204 over the entire circumference, and at least a portion of it can be fixed as long as the vibration of the vibration plate 203 can be obtained.

[0030] The container setting part 205 is configured to be able to set the reaction container 105. Specifically, it has a storage part capable of storing the reaction container 105 inside, and is fixed to the approximate center of the vibration plate 203. In other words, the container setting part 205 is set to the approximate center of the flexural vibrator formed by bonding the piezoelectric element 202 and the vibration plate 203. The container setting part 205 is set on the vibration plate 203 so that it can vibrate together with the flexural vibration of the vibration plate 203. It is preferred that the container setting part 205 is fixed to a position where the vibration amplitude of the vibration plate 203 is approximately the maximum when an AC voltage of a predetermined frequency is applied to the piezoelectric element 202.

[0031] The control unit 206 is connected to the electrodes of the piezoelectric element 202. The control unit 206 functions as a power supply unit that supplies an AC voltage to the piezoelectric element 202, and also constitutes a detection unit and a mass calculation unit. The detection unit detects the resonance frequency f of the resonance unit 207 composed of the piezoelectric element 202, the vibration plate 203, the container setting unit 205, and the reaction container 105, and the mass calculation unit calculates the mass of the reaction container 105 based on the detected resonance frequency. By detecting the absolute value |Δf| of the change in the resonance frequency before and after dispensing, the change Δm of the mass before and after dispensing, that is, the mass of the discharged liquid, can be measured (refer to Figure 3 ).

[0032] When the resonator 207 vibrates near the resonant frequency of a specific vibration mode, the vibration system can be approximated to a spring-mass damper system with 1 degree of freedom. At this time, the resonant frequency fr at which the vibration velocity v becomes the maximum when the regulated excitation force F is applied to the vibration system is expressed by the following [Formula 1]. Here, k and m are the equivalent spring constant and equivalent mass of the vibration system, respectively.

[0033] [Formula 1]

[0034]

[0035] When the mass of the vibration system changes by Δm (dispensing mass) by discharging liquid into the reaction container 105, when the dispensing mass Δm is sufficiently small compared to the mass m of the entire vibration system, the change Δf of the resonance frequency fr is expressed by Formula 2. The difference Δf between the resonance frequencies before and after dispensing is proportional to the dispensing mass Δm, so the dispensing mass Δm can be calculated based on the change Δf. The reaction container 105 has a mass deviation due to manufacturing deviation. The mass deviation of the reaction container 105 is so large that it cannot be ignored relative to the dispensing mass. By using the difference Δf between the resonance frequencies before and after dispensing, the influence of the mass deviation of the reaction container 105 can be reduced to calculate the dispensing mass Δm.

[0036] [Formula 2]

[0037]

[0038] In order to avoid the influence of disturbance vibration caused by the operation of the automatic analyzer 1, the resonant frequency fr used by the mass sensor 2 in the measurement of the dispensing amount is preferably 1 kHz or more, and as a vibration frequency that can ignore the deformation of the reaction container 105, it is preferably 6 kHz or less, which is the primary natural vibration frequency of the reaction container 105. By making the vibration plate 203 and the piezoelectric element 202 in the shape of a circular plate and utilizing the flexural vibration by fixing the outer periphery of the vibration plate 203, the resonant frequency of the resonance part can be 1 kHz to 6 kHz with a small and lightweight structure that can be mounted on the automatic analyzer.

[0039] The reaction container 105 is set (installed) on the container setting part 205 or removed (detached) from the container setting part 205 by the jig 108. When the reaction container 105 is loaded and unloaded, an external force much larger than the load caused by the dispensed mass is applied to the mass sensor 2. Since the outer periphery of the vibration plate 203 is supported by the fixing part 204, the load caused by loading and unloading the reaction container 105 is dispersed to the entire outer periphery, thereby having the effect of preventing the vibration plate 203 and the piezoelectric element from being damaged by the external force.

[0040] As described above, for the reaction container 105 arranged at the discharge position 112, when a predetermined amount of liquid is not dispensed into the reaction container 105 at the discharge position 112 due to an abnormal operation of the dispensing mechanism 111, the mass sensor 2 can detect the abnormality of the dispensing amount. Specifically, according to the comparison result between the predetermined dispensing amount and the dispensing amount calculated by the control unit 206, the control unit 206 can determine whether the dispensing amount is normal.

[0041] Reference Figure 4 The flow chart of the first embodiment is used to describe the operation of measuring the mass of the liquid dispensed into the reaction container 105 in the automatic analyzer 1. When the automatic analyzer 1 performs automatic analysis, first, the empty reaction container 105 is set in the container setting part 205 of the mass sensor 2 (step S301). Then, in the state where the empty reaction container 105 is set, the resonance frequency f1 is measured in the mass sensor 2 (step S302).

[0042] Next, the sample and the reagent (liquid) are discharged from the reaction container 105 (step S303), and then the resonance frequency f2 of the reaction container 105 after the discharge is measured by the mass sensor 2 (step S304). Then, based on the measured resonance frequencies f1 and f2, the mass (Δm) of the liquid discharged in step S303 is calculated (step S305). When the difference between the calculated mass and the predetermined discharge amount exceeds a threshold value, the control unit 206 determines that the discharge amount is abnormal, and displays the situation on a display (not shown), etc., thereby being able to report it to the operator.

[0043] In this way, the automatic analyzer 1 of the first embodiment calculates the mass of the liquid discharged into the reaction container 105 based on the first resonance frequency of the resonance part at the time point before the liquid is discharged into the reaction container and the second resonance frequency of the resonance part at the time point after the liquid is discharged. The mass sensor 2 includes a fixing part 204, a vibration plate 203 at least part of which is fixed to the fixing part 204, a piezoelectric element 202 joined to the vibration plate 203, and a container setting part 205 supported by the vibration plate 203 and configured to be able to set the reaction container 105. The resonance frequency f of the resonance part 207 composed of the piezoelectric element 202, the vibration plate 203, the container setting part 205, and the reaction container 105 changes according to the mass of the liquid dispensed into the reaction container 105, so the control part 206 can detect the mass of the dispensed liquid by detecting the change in the resonance frequency f, and can detect abnormality. By having such a structure, even if there is a manufacturing variation in the reaction container 105, the mass of the discharged liquid can be accurately measured without being affected by it.

[0044] As described above, according to the automatic analyzer 1 and the mass sensor 2 of the first embodiment, a predetermined aliquot amount of a specimen or a sample can be accurately dispensed, thereby ensuring the reliability of the analysis result.

[0045] [Second Embodiment]

[0046] Next, refer to Figure 5 The automatic analyzer of the second embodiment is described. The overall structure of the automatic analyzer 1 of the second embodiment may be the same as that of the first embodiment ( Figure 1 ), the structure of the mass sensor 2 may also be the same ( Figure 2 ). However, the automatic analyzer 1 of the second embodiment is different from the first embodiment in the measurement operation of the mass of the liquid dispensed into the reaction container 105. Specifically, in the automatic analyzer 1 of the second embodiment, the liquid (specimen and reagent) is discharged into one reaction container 105 multiple times, and it is determined whether the discharge mass of the liquid in each discharge operation is normal.

[0047] Reference Figure 5 The operation of measuring the mass of the liquid dispensed into the reaction container 105 in the automatic analyzer 1 of the second embodiment will be described with reference to the flowchart of FIG. 1 . Steps S401 to 405 are the same as steps S301 to 305 of the first embodiment, and therefore repeated descriptions are omitted here.

[0048] In step S406, when a part of the multiple discharge actions to a reaction container 105 mounted on the mass sensor 2 has not been completed and liquid to be discharged remains (no), move to step S407 and replace the resonant frequency f2 in the previous measurement with f1 (that is, the resonant frequency f2 after the discharge action in the previous discharge and mass measurement is set to the resonant frequency f1 before the discharge action in the next measurement).

[0049] Next, in step S403, a new discharge of liquid is performed on the reaction container 105, and the resonance frequency f2 after the discharge is re-measured (step S404). Then, based on the resonance frequency f1 (before the new discharge action) set in step S407 and the newly obtained resonance frequency f2, the discharge mass of the liquid in the new discharge action is calculated (step S405). The above operation is repeated until the prescribed multiple discharge actions are completed.

[0050] As described above, in the automatic analyzer 1 of the second embodiment, the discharge operation to one reaction container 105 is performed multiple times, and the discharge mass of each of the multiple discharge operations is measured by the mass sensor 2. Therefore, according to the second embodiment, in addition to being able to obtain the same effects as the first embodiment, each of the multiple discharge operations can be managed, so the discharge operation can be managed more accurately.

[0051] The embodiments of the present invention are described above, but these embodiments are presented as examples and are not intended to limit the scope of the invention. These new embodiments can be implemented in various other ways, and various omissions, substitutions, and changes can be made without departing from the scope of the invention. These embodiments and their variations are included in the scope and spirit of the invention, and are included in the invention described in the scope of patent protection and its equivalent.

[0052] Description of Reference Numerals

[0053] 1…Automatic analysis device

[0054] 2…Mass sensor

[0055] 101…reagent container

[0056] 102…Reagent disk

[0057] 103…Specimen container

[0058] 104…Specimen plate

[0059] 105…Reaction vessel

[0060] 106···Incubator

[0061] 107…Reaction vessel tray

[0062] 108…Clamp

[0063] 109…Detection unit

[0064] 110…Reaction vessel waste port

[0065] 111…Injection mechanism

[0066] 112…Discharge position

[0067] 117…Cleaning tank

[0068] 201…Discharge of liquid

[0069] 202…Piezoelectric element

[0070] 203…Vibration plate

[0071] 204…Fixed part

[0072] 205…Container installation part

[0073] 206…Control Department

[0074] 207 ...resonance section.

Claims

1. An automatic analysis device, characterized in that: have: a reagent holding unit that holds a reagent container containing a reagent; a specimen holding unit that holds a specimen container containing the specimen; A dispensing mechanism that dispenses the reagent and the sample into a reaction container; and a mass sensor, which determines the mass of the reaction vessel, The mass sensor has: Fixed part; a vibration plate, at least a portion of which is fixed to the fixing portion; a piezoelectric element joined to the vibration plate; and The container setting portion is supported on the vibration plate and is configured to be able to set the reaction container into which the liquid to be measured is discharged.

2. The automatic analysis device according to claim 1, characterized in that The vibration plate, the container installation part and the reaction container constitute a resonance part. The mass of the liquid discharged into the reaction container is calculated based on the first resonance frequency of the resonance section at a time point before the liquid is discharged into the reaction container and the second resonance frequency of the resonance section at a time point after the liquid is discharged into the reaction container.

3. The automatic analysis device according to claim 2, characterized in that: The dispensing mechanism performs a plurality of discharge operations on one reaction container, and the mass sensor measures the mass of the reaction container for each of the discharge operations. The mass sensor sets the previous second resonance frequency as the first resonance frequency for each of the plurality of discharge operations, and sets the resonance frequency measured after a new discharge operation as the second resonance frequency.

4. The automatic analysis device according to claim 1, characterized in that The vibration plate is in the shape of a circular plate. The fixing portion fixes at least a portion of an outer peripheral portion of the vibration plate.

5. The automatic analysis device according to any one of claims 1 to 4, characterized in that: The container installation portion is fixed to a substantially center of the vibration plate.

6. The automatic analysis device according to any one of claims 1 to 4, characterized in that: The container installation portion is fixed at a position where the vibration amplitude of the vibration plate is substantially maximized when an alternating voltage of a predetermined frequency is applied to the piezoelectric element.

7. A mass sensor for measuring the mass of a liquid discharged into a reaction container, characterized in that: The mass sensor has: Fixed part; a vibration plate, at least a portion of which is fixed to the fixing portion; a piezoelectric element joined to the vibration plate; and The container setting portion is supported on the vibration plate and is configured to be able to set the reaction container to which the discharged reagent and the sample are to be placed.

8. The mass sensor according to claim 7, characterized in that: The vibration plate, the container installation part and the reaction container constitute a resonance part. The mass of the liquid discharged into the reaction container is calculated based on the first resonance frequency of the resonance section at a time point before the liquid is discharged into the reaction container and the second resonance frequency of the resonance section at a time point after the liquid is discharged into the reaction container.

9. The mass sensor according to claim 8, characterized in that: The dispensing mechanism performs a plurality of discharge operations on one reaction container, and the mass sensor measures the mass of the reaction container for each of the discharge operations. The mass sensor sets the previous second resonance frequency as the first resonance frequency for each of the plurality of discharge operations, and sets the resonance frequency measured after a new discharge operation as the second resonance frequency.

10. The mass sensor according to claim 7, characterized in that: The vibration plate is in the shape of a circular plate. The fixing portion fixes at least a portion of an outer peripheral portion of the vibration plate.

11. The mass sensor according to any one of claims 7 to 10, characterized in that: The container installation portion is fixed to a substantially center of the vibration plate.

12. The mass sensor according to any one of claims 7 to 10, characterized in that: The container installation portion is fixed at a position where the vibration amplitude of the vibration plate is substantially maximized when an alternating voltage of a predetermined frequency is applied to the piezoelectric element.

Images