Automated analyzer and mass sensor

Abstract

To accurately dispense a fixed dispensation amount specimen and sample to ensure the reliability of an analysis result.SOLUTION: An autoanalyzer comprises: a reagent holding unit that holds reagent containers storing a reagent; a specimen holding unit that holds specimen containers storing a specimen; a dispensation mechanism that dispenses the reagent and the specimen to reaction containers; and a mass sensor that measures the mass of the reaction containers. The mass sensor includes a stationary part, a diaphragm that is at least partially fixed to the stationary part, a piezoelectric element that is joined to the diaphragm, and a container installation part that is supported on the diaphragm and allows installation of reaction containers to which liquid to be measured is discharged.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to an automatic analyzer and a mass sensor.

Background Art

[0002] Quantitative measurements of the concentrations of chemical substances, such as proteins, lipids, sugars, ions, and various components constituting these, contained in body fluid components such as blood and urine, are carried out clinically. An automatic analyzer is known as a device for automating the processes necessary for this measurement (for example, quantitative dispensing of a specimen sample, mixing with a reagent, determination of the reaction result, measurement of changes in substances contained in the reagent, etc.).

[0003] The automatic analyzer performs component analysis of a specimen by reacting a specified amount of the specimen and a reagent in a reaction vessel and measuring the absorbance or luminescence of the specimen. Inside the device, a dispensing mechanism for distributing the specimen and the reagent to the reaction vessels is installed. The dispensing mechanism is required to be configured to dispense a predetermined amount of the specimen and the reagent.

[0004] In an automatic analyzer, the mass of the 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 some abnormality occurs in the dispensing mechanism and the analysis is performed without obtaining the predetermined dispensing amount, a correct analysis result cannot be obtained.

[0005] In addition, since the automatic analyzer has various motors and movable parts including a dispensing mechanism, there is a problem that there are many disturbances due to vibration. In order to measure the accurate masses of the dispensed specimen and reagent without being affected by disturbance vibration, it is also conceivable to install a vibration isolation table or the like and provide an electronic balance or the like on the vibration isolation table. However, since the vibration isolation table is large, providing a vibration isolation table for the automatic analyzer is not practical because it causes the automatic analyzer to become larger. From such a situation, in order to ensure the reliability of the analysis results, an automatic analyzer and a mass sensor that accurately dispense the specimen and the sample and ensure the reliability of the analysis results are required.

Prior Art Documents

[0006] [Patent Document 1] Japanese Patent Publication No. 2010-217048 [Overview of the project] [Problems that the invention aims to solve]

[0007] The present invention provides an automated analyzer and a mass sensor that can accurately dispense predetermined amounts of specimens and samples to ensure the reliability of analytical results. [Means for solving the problem]

[0008] The automated analyzer according to the present invention comprises a reagent holding unit for holding reagent containers for storing reagents, a sample holding unit for holding sample containers for storing samples, a dispensing mechanism for dispensing the reagents and samples into a reaction vessel, and a mass sensor for measuring the mass of the reaction vessel. The mass sensor comprises a fixed unit, a diaphragm to which at least a portion is fixed to the fixed unit, a piezoelectric element joined to the diaphragm, and a container mounting unit configured to accommodate the reaction vessel supported by the diaphragm and from which the liquid to be measured is discharged.

[0009] The mass sensor according to the present invention is a mass sensor for measuring the mass of a liquid discharged into a reaction vessel, and is characterized by comprising: a fixed part; a diaphragm to which at least a portion is fixed to the fixed part; a piezoelectric element joined to the diaphragm; and a container mounting part supported by the diaphragm and configured to accommodate a reaction vessel from which reagents and samples are discharged. [Effects of the Invention]

[0010] According to the present invention, it is possible to provide an automated analyzer and a mass sensor that can accurately dispense predetermined amounts of specimens and samples to ensure the reliability of the analysis results. [Brief explanation of the drawing]

[0011] [Figure 1] This is a schematic diagram of the automated analyzer 1 according to the first embodiment. [Figure 2] This is a perspective view showing the detailed configuration of mass sensor 2. [Figure 3] This graph illustrates the operation of mass sensor 2. [Figure 4] This is a flowchart illustrating the operation of the automated analyzer 1 according to the first embodiment. [Figure 5] This is a flowchart illustrating the operation of the automated analyzer 1 according to the second embodiment. [Modes for carrying out the invention]

[0012] This embodiment will be described below with reference to the attached drawings. In the attached drawings, functionally identical elements may be indicated by the same or corresponding numbers. The attached drawings show embodiments and implementation examples in accordance with the principles of this disclosure, but they are for the purpose of understanding this disclosure and are not to be used in any way to restrict the interpretation of this disclosure. The descriptions in this specification are merely typical examples and do not limit the claims or applications of this disclosure in any way.

[0013] While this embodiment is described in sufficient detail for those skilled in the art to implement the disclosure, it is important to understand that other implementations and forms are possible, and that the configuration and structure can be modified and various elements replaced without departing from the scope and spirit of the technical idea of ​​this disclosure. Therefore, the following description should not be construed as limiting to this.

[0014] [First Embodiment] Referring to Figure 1, the overall configuration of the automated analyzer 1 of the first embodiment will be described. This automated analyzer 1 is generally composed of, as an example, a reagent disk (reagent holding unit) 102, a sample disk (sample holding unit) 104, an incubator 106, a reaction vessel tray 107, a gripper 108, a detection unit 109, a reaction vessel waste port 110, a dispensing mechanism 111, a mass sensor 2, and a washing tank 117.

[0015] The reagent disk 102 is a reagent holder that holds a reagent container 101 containing reagents used for analysis. The sample disk 104 is a sample holder that holds a sample container 103 containing a sample to be tested. The reagent disk 102 and the sample disk 104 are configured to be movable (for example, rotatable around a rotation axis) by moving mechanisms 102a and 104a, respectively. As the reagent disk 102 and the sample disk 104 move, the dispensing mechanism 111 can access the reagent container 101 and the sample container 103 and aspirate the reagent and the sample (liquid). After aspiration, the dispensing mechanism 111 can access the reaction vessel 105 located at the discharge position 112 of the mass sensor 2 and discharge the aspirated liquid.

[0016] The incubator 106 has the function of promoting the reaction in the reaction vessel 105, into which reagents and samples have been injected, in a temperature-controlled environment. The reaction vessel tray 107 holds unused reaction vessels 105. The gripper 108 has the function of grasping the reaction vessel 105 and transporting it to the mass sensor 2, detection unit 109, reaction vessel disposal port 110, etc. The detection unit 109 receives the reaction vessel 105 after a predetermined reaction time in the incubator 106 and performs the analysis of the sample. The reaction vessel disposal port 110 constitutes a disposal section for discarding the used reaction vessel 105 after the analysis is completed. The washing tank 117 can wash the dispensing mechanism 111. Washing prevents the carryover of components when dispensing different liquids.

[0017] The mass sensor 2 is a measuring unit that measures the mass of the liquid discharged into the reaction vessel 105 located at the discharge position 112. Figure 2 is a perspective view showing the details of the configuration of the mass sensor 2. This mass sensor 2 is configured, for example, with a piezoelectric element 202, a vibrating plate 203, a fixing part 204, a container mounting part 205, and a control unit 206.

[0018] As shown in FIG. 2, for example, the piezoelectric element 202 can be joined at a position concentric with the diaphragm 203 on one or both sides of the diaphragm 203 configured in a disc shape as an example. The piezoelectric element 202 is polarized in the thickness direction. When an alternating voltage is applied to the electrodes formed on both sides, the piezoelectric element 202 expands and contracts, causing the diaphragm 203 to generate a flexural vibration with the center position of the disc as the antinode. Note that the diaphragm 203 can be made of a metal material such as aluminum or titanium, for example.

[0019] The fixing portion 204 constitutes the base portion of the mass sensor 2. For example, as shown in FIG. 2, it has an upper fixing member and a lower fixing member, and the outer peripheral portion of the diaphragm 203 can be fixed by sandwiching it from above and below with the upper and lower fixing members. That is, the diaphragm 203 is configured to obtain a vibration with the fixing portion 204 as the fixed end. The outer peripheral portion of the diaphragm 203 does not need to be fixed to the fixing portion 204 over the entire circumference, and it is sufficient that at least a part is fixed as long as the vibration of the diaphragm 203 can be obtained.

[0020] The reaction vessel installation portion 205 is configured to be able to install the reaction vessel 105. Specifically, it has a housing portion inside which the reaction vessel 105 can be housed, and is fixed to approximately the center of the diaphragm 203. In other words, the reaction vessel installation portion 205 is installed at approximately the center of the flexural vibrator formed by bonding the piezoelectric element 202 and the diaphragm 203. The reaction vessel installation portion 2 is installed on the diaphragm 203 so as to be able to vibrate together with the flexural vibration of the diaphragm 203. The reaction vessel installation portion 205 is preferably fixed at a position where the vibration amplitude of the diaphragm 203 becomes almost maximum when an alternating voltage of a predetermined frequency is applied to the piezoelectric element 202.

[0021] A 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 alternating voltage to the piezoelectric element 202, and also constitutes a detection unit that detects the resonance frequency f of a resonance unit 207 composed of the piezoelectric element 202, the diaphragm 203, the container installation unit 205, and the reaction container 105, and a mass calculation unit that calculates the mass of the reaction container 105 based on the detected resonance frequency. By detecting the absolute value |Δf| of the change amount of the resonance frequency before and after dispensing, the change amount Δm of the mass before and after ejection, that is, the mass of the ejected liquid can be measured (see Fig. 3).

[0022] When the resonance unit 207 vibrates near the resonance frequency of a specific vibration mode, the vibration system can be approximated as a one-degree-of-freedom spring-mass-damper system. At this time, the resonance frequency fr at which the vibration velocity v becomes maximum when a harmonic excitation force F is applied to the vibration system is represented by the following [Equation 1]. Here, k and m are the equivalent spring constant and the equivalent mass of the vibration system, respectively.

[0023]

Equation

[0024] When liquid is ejected into the reaction container 105 and the mass of the vibration system changes by Δm (dispensing mass), the change amount Δf of the resonance frequency fr is represented by Equation 2 when the dispensing mass Δm is sufficiently smaller than the mass m of the entire vibration system. Since the difference Δf between the resonance frequencies before and after dispensing is proportional to the dispensing mass Δm, the dispensing mass Δm can be calculated based on the change amount Δf. Due to manufacturing variations, the mass of the reaction container 105 has variations. The mass variation of the reaction container 105 is so large that it cannot be ignored with respect to the dispensing mass. By using the difference Δf between the resonance frequencies before and after dispensing, the influence of the mass variation of the reaction container 105 can be reduced and the dispensing mass Δm can be calculated.

[0025]

Equation

[0026] The resonant frequency fr used by the mass sensor 2 to measure the dispensing volume is preferably 1 kHz or higher to avoid the influence of disturbance vibrations caused by the operation of the automatic analyzer 1, and preferably 6 kHz or lower, which is the first natural frequency of the reaction vessel 105, as this frequency allows the deformation of the reaction vessel 105 to be ignored. By using a disc shape for the diaphragm 203 and piezoelectric element 202, and by utilizing flexural vibration with the outer circumference of the diaphragm 203 fixed, a compact and lightweight configuration that can be mounted on an automatic analyzer can be achieved, with a resonant frequency of 1 kHz to 6 kHz.

[0027] The reaction vessel 105 is installed (attached) to the vessel mounting section 205 by the gripper 108, and is also removed (detached) from the vessel mounting section 205. When the reaction vessel 105 is attached or detached, an external force much larger than the load due to the dispensing mass is applied to the mass sensor 2. By supporting the outer circumference of the vibrating plate 203 with the fixing section 204, the load due to the attachment or detachment of the reaction vessel 105 is distributed across the entire outer circumference, thus preventing the vibrating plate 203 and piezoelectric element from being damaged by the external force.

[0028] As described above, if the specified amount of liquid is not dispensed to the reaction vessel 105 located at the discharge position 112 due to abnormal operation of the dispensing mechanism 111, the mass sensor 2 can detect the abnormality in the dispensed amount. Specifically, the control unit 206 can determine whether the dispensed amount is normal or not based on the result of comparing the predetermined discharge amount with the discharge amount calculated by the control unit 206.

[0029] Referring to the flowchart in Figure 4, the operation of measuring the mass of the liquid dispensed into the reaction vessel 105 in the automatic analyzer 1 of the first embodiment will be explained. When automatic analysis is performed by the automatic analyzer 1, first, an empty reaction vessel 105 is placed in the container mounting section 205 of the mass sensor 2 (step S301). Then, with the empty reaction vessel 105 in place, the resonance frequency f1 is measured in the mass sensor 2 (step S302).

[0030] Next, the sample and reagent (liquid) are dispensed into the reaction vessel 105 (step S303), and then the resonant frequency f2 of the reaction vessel 105 after dispensing is measured by the mass sensor 2 (step S304). Based on the measured resonant frequencies f1 and f2, the mass (Δm) of the liquid dispensed in step S303 is calculated (step S305). If the difference between the calculated mass and the predetermined dispensing volume exceeds a threshold, the control unit 206 determines that the dispensing volume is abnormal and can notify the operator by displaying this information on a display (not shown) or the like.

[0031] Thus, the automatic analyzer 1 of the first embodiment calculates the mass of the liquid discharged into the reaction vessel 105 based on the first resonant frequency of the resonant section before the liquid is discharged into the reaction vessel and the second resonant frequency of the resonant section after the liquid is discharged. The mass sensor 2 comprises a fixed part 204, a diaphragm 203 to which at least a part is fixed to the fixed part 204, a piezoelectric element 202 joined to the diaphragm 203, and a container mounting part 205 supported by the diaphragm 203 and configured to accommodate the reaction vessel 105. As the mass of the liquid dispensed into the reaction vessel 105 changes the resonant frequency f of the resonant section 207, which is composed of the piezoelectric element 202, the diaphragm 203, the container mounting part 205, and the reaction vessel 105, the control unit 206 can detect the mass of the dispensed liquid and detect any abnormalities by detecting this change in resonant frequency f. This configuration makes it possible to accurately measure the mass of the discharged liquid without being affected by manufacturing variations in the reaction vessel 105.

[0032] As described above, the automated analyzer 1 and mass sensor 2 of the first embodiment can accurately dispense predetermined amounts of specimens and samples, thereby ensuring the reliability of the analysis results.

[0033] [Second Embodiment] Next, with reference to Figure 5, an automated analyzer according to the second embodiment will be described. The automated analyzer 1 of the second embodiment may have the same overall configuration as the first embodiment (Figure 1), and the structure of the mass sensor 2 may also be the same (Figure 2). However, the automated analyzer 1 of this second embodiment differs from the first embodiment in the operation of measuring the mass of the liquid dispensed into the reaction vessel 105. Specifically, in the automated analyzer 1 of this second embodiment, the liquid (sample and reagent) is dispensed into a single reaction vessel 105 multiple times, and it is determined whether the dispensed liquid mass is normal for each dispensing operation.

[0034] Referring to the flowchart in Figure 5, the operation of measuring the mass of the liquid dispensed into the reaction vessel 105 in the automated analyzer 1 of the second embodiment will be explained. Steps S401 to S405 are the same as steps S301 to S305 of the first embodiment, so redundant explanations will be omitted here.

[0035] If, in step S406, some of the multiple dispensing operations to the reaction vessel 105 mounted on the mass sensor 2 have not yet been completed and there is still liquid to be dispensed (NO), the process proceeds to step S407, where the resonance frequency f2 from the previous measurement is replaced with f1 (i.e., the resonance frequency f2 after the dispensing operation in the previous dispensing and mass measurement is set to the resonance frequency f1 before the dispensing operation in the next measurement).

[0036] Next, in step S403, a new liquid is discharged into the reaction vessel 105, and the resonant frequency f2 after the discharge is measured again (step S404). Then, based on the resonant frequency f1 (before the new discharge operation) set in step S407 and the newly obtained resonant frequency f2, the discharge mass of the liquid in the new discharge operation is calculated (step S405). The above is repeated until a specified number of discharge operations are completed.

[0037] As described above, in the automatic analyzer 1 of the second embodiment, the dispensing operation into a single reaction vessel 105 is performed multiple times, and the dispensing mass for each of these multiple dispensing operations is measured by the mass sensor 2. Therefore, according to the second embodiment, in addition to obtaining the same effects as the first embodiment, each of the multiple dispensing operations is managed, so the dispensing operation can be managed more accurately.

[0038] Although embodiments of the present invention have been described above, these embodiments are presented as examples and are not intended to limit the scope of the invention. These novel embodiments can be implemented in various other forms, and various omissions, substitutions, and modifications can be made without departing from the spirit of the invention. These embodiments and their variations are included in the scope and spirit of the invention, as well as in the claims of the invention and its equivalents. [Explanation of Symbols]

[0039] 1…Automatic analyzer 2…Mass sensor 101…Reagent container 102…Reagent disk 103... Specimen container 104... Sample disk 105…Reaction vessel 106... Incubator 107…Reaction vessel tray 108... Grippa 109...Detection Unit 110... Reaction vessel waste port 111… Dispensing mechanism 112...Discharge position 117... Washing tank 201…Discharge liquid 202... Piezoelectric element 203…Diaphragm 204…Fixed part 205…Container installation part 206... Control Unit 207...Resonance section

Claims

1. A reagent holder that holds a reagent container for storing reagents, A specimen holding unit that holds a specimen container containing specimens, A dispensing mechanism for dispensing the reagent and the sample into a reaction vessel, A mass sensor for measuring the mass of the reaction vessel and Equipped with, The aforementioned mass sensor is The fixing part, A diaphragm, to which at least a portion is fixed to the aforementioned fixed part, A piezoelectric element joined to the diaphragm, A container mounting section is configured to be able to install the reaction vessel, which is supported by the diaphragm and from which the liquid to be measured is discharged. Equipped with, The diaphragm, the container mounting section, and the reaction vessel constitute the resonant section. The aforementioned mass sensor is The difference between the first resonant frequency of the resonant portion before the liquid is discharged into the reaction vessel and the second resonant frequency of the resonant portion after the liquid is discharged into the reaction vessel, The equivalent spring constant of the resonant part, The equivalent mass of the resonant part, Based on the relationship between the two factors, the mass of the liquid discharged into the reaction vessel is calculated by calculating the change in mass of the resonant part before and after the liquid is discharged into the reaction vessel. An automated analyzer characterized by the following features.

2. The dispensing mechanism performs multiple dispensing operations on a single reaction vessel, and the mass sensor measures the mass of the reaction vessel after each dispensing operation. The automatic analyzer according to claim 1, wherein the mass sensor sets the previous second resonance frequency as the first resonance frequency for each of the multiple dispensing operations, and sets the resonance frequency measured after the new dispensing operation as the second resonance frequency.

3. The diaphragm is disc-shaped, The automatic analyzer according to claim 1, wherein the fixing part fixes at least a portion of the outer periphery of the diaphragm.

4. The container mounting section is fixed approximately in the center of the diaphragm. The automated analyzer according to any one of claims 1 to 3.

5. The container mounting section is fixed in a position where the vibration amplitude of the diaphragm is approximately at its maximum when an AC voltage of a predetermined frequency is applied to the piezoelectric element. The automated analyzer according to any one of claims 1 to 3.

6. A mass sensor for measuring the mass of a liquid discharged into a reaction vessel, The fixing part, A diaphragm, to which at least a portion is fixed to the aforementioned fixed part, A piezoelectric element joined to the diaphragm, A container mounting section is configured to accommodate a reaction vessel supported by the aforementioned vibrating plate, from which reagents and samples are discharged. Equipped with, The diaphragm, the container mounting section, and the reaction vessel constitute the resonant section. The aforementioned mass sensor is The difference between the first resonant frequency of the resonant portion before the liquid is discharged into the reaction vessel and the second resonant frequency of the resonant portion after the liquid is discharged into the reaction vessel, The equivalent spring constant of the resonant part, The equivalent mass of the resonant part, Based on the relationship between the two factors, the mass of the liquid discharged into the reaction vessel is calculated by calculating the change in mass of the resonant part before and after the liquid is discharged into the reaction vessel. A mass sensor characterized by the following features.

7. The dispensing mechanism performs multiple dispensing operations on a single reaction vessel, and the mass sensor measures the mass of the reaction vessel after each dispensing operation. The mass sensor according to claim 6, wherein, for each of the multiple dispensing operations, the mass sensor sets the previous second resonance frequency to the first resonance frequency, and sets the resonance frequency measured after the new dispensing operation to the second resonance frequency.

8. The diaphragm is disc-shaped, The mass sensor according to claim 6, wherein the fixing portion fixes at least a part of the outer periphery of the diaphragm.

9. The container mounting section is fixed approximately in the center of the diaphragm. The mass sensor according to any one of claims 6 to 8.

10. The container mounting section is fixed in a position where the vibration amplitude of the diaphragm is approximately at its maximum when an AC voltage of a predetermined frequency is applied to the piezoelectric element. The mass sensor according to any one of claims 6 to 8.

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