Automated analysis device

Abstract

An object of the present disclosure is to provide an automatic analysis device capable of reducing the influence of a previously produced mixed solution when a new mixed solution is produced. The automatic analysis device of the present disclosure is configured to produce a second mixed solution after a first mixed solution is produced, and introduce a buffer reagent for reducing the influence of the first reagent remaining in a mixed solution chamber when the second mixed solution is produced, to the mixed solution chamber based on the characteristics of the first mixed solution (see FIG. 2B).

Description

Technical Field

[0001] This disclosure relates to an automatic analysis device. Background Technology

[0002] An automated analytical apparatus is, for example, a device that reacts a sample with reagents and analyzes the reaction to determine the composition and properties of the sample. Sometimes, a mixture is prepared by mixing multiple reagents. In this case, multiple reagents are introduced into a mixing chamber, where they are mixed to prepare a mixture, which is then supplied to the analytical process.

[0003] Patent Document 1 describes a reagent preparation apparatus. This document, with the subject matter of "easily preparing reagents with high-precision concentrations using a simple structure," discloses the following technology: "It is characterized by comprising: a preparation vessel for containing the reagent and a diluent; a reagent supply unit for supplying a predetermined amount of reagent to the preparation vessel; a diluent supply unit for supplying the preparation vessel with a diluent amount less than the amount required to dilute the supplied reagent to the desired concentration; a diluent replenishment unit for replenishing the preparation vessel with an arbitrary amount of diluent; a detection unit for detecting the reagent concentration within the vessel; and a control unit for controlling the replenishment operation of the diluent replenishment unit. When the detected reagent concentration is higher than the desired concentration, the control unit repeatedly performs the following control: calculating the amount of diluent to replenish the reagent concentration to the desired concentration based on the difference between the detected concentration and the desired concentration, and replenishing the preparation vessel with a diluent amount less than the calculated amount until the desired concentration is reached." (See abstract).

[0004] Existing technical documents

[0005] Patent documents

[0006] Patent Document 1: Japanese Patent Application Publication No. 9-033538 Summary of the Invention

[0007] The technical problem that the invention aims to solve

[0008] In Patent Document 1, the desired reagent is prepared by adjusting the reagent to a high concentration in the preparation tank 7 (mixing chamber) and then further injecting pure water. When the mixture is prepared in this way within the mixing chamber, the residue remaining in the mixing chamber may have an impact on the next preparation of the mixture.

[0009] This disclosure is made in view of the above-mentioned problems, and its purpose is to provide an automatic analysis apparatus that can mitigate the influence of previously prepared mixtures when preparing new mixtures.

[0010] Technical means for solving technical problems

[0011] The automatic analysis apparatus disclosed herein is configured to produce a second mixture after producing a first mixture, and based on the characteristics of the first mixture, a buffer reagent for mitigating the influence of the first reagent remaining in the mixing chamber during the production of the second mixture is introduced into the mixing chamber.

[0012] Invention Effects

[0013] According to the automatic analysis apparatus disclosed herein, the influence of previously prepared mixtures can be mitigated when preparing mixtures. Other features, advantages, structures, etc., of this disclosure will become clear from the following detailed description. Attached Figure Description

[0014] Figure 1 This is a schematic diagram showing an example of the structure of the automatic analysis device 100 according to Embodiment 1.

[0015] Figure 2A This is a schematic diagram illustrating the steps involved in preparing a mixture using a conventional automated analyzer.

[0016] Figure 2B This is a schematic diagram illustrating the steps of the automatic analysis device 100 in Embodiment 1 to prepare a mixture.

[0017] Figure 3 An example illustrating the volume of buffer reagent 133 is shown.

[0018] Figure 4 This is a diagram illustrating the steps for preparing the mixture in Embodiment 2.

[0019] Figure 5 An example illustrating the volume of buffer reagent 133 is shown.

[0020] Figure 6 This is an example of the user interface provided by the control unit 161. Detailed Implementation

[0021] <Implementation Method 1>

[0022] Figure 1 This is a schematic diagram illustrating a structural example of the automatic analysis apparatus 100 according to Embodiment 1 of the present invention. The automatic analysis apparatus 100 is a device that analyzes the reaction between a sample and a reagent to determine the characteristics of the sample. The automatic analysis apparatus 100 includes a mixing chamber 110, a reagent introduction mechanism 120, a reagent container 130, a mixing dispensing mechanism 140, a reaction container 150, a control unit 161, and a storage unit 162.

[0023] The mixing chamber 110 is a container used to prepare a mixture by introducing multiple reagents into it (sometimes only one reagent is used). The reagent introduction mechanism 120 draws reagent from the reagent container 130 and introduces it into the mixing chamber 110. The reagent introduction mechanism 120 may be constructed, for example, by a liquid dispensing nozzle. The mixing chamber 110 and the reagent container 130 may be configured according to the type of reagent or mixture.

[0024] The mixing solution dispensing mechanism 140 dispenses the mixing solution in the mixing chamber 110 into the reaction vessel 150. The sample is introduced into the reaction vessel 150 through a sample introduction mechanism (not shown), and the mixing solution and the sample react on the reaction vessel 150.

[0025] The control unit 161 controls the various components of the automatic analysis device 100 (e.g., the reagent introduction mechanism 120 and the mixture dispensing mechanism 140). The storage unit 162 is a storage device that stores the data used by the control unit 161. The control unit 161 can be configured using hardware such as circuit devices with this function installed, or it can be configured by using a computing device such as a CPU (Central Processing Unit) to execute software with this function installed.

[0026] Figure 2A This is a schematic diagram illustrating the steps of preparing a mixture using a conventional automated analytical device. In the conventional mixture preparation process, a first mixture is prepared by introducing a first reagent 131 into the mixture chamber 110. Figure 2A (Left) The first mixture is drawn from the mixing chamber 110 and supplied to subsequent processes. At this time, the first mixture remains in the mixing chamber 110 as a residual liquid 131'. The automated analyzer also prepares a second mixture by introducing a second reagent 132 into the mixing chamber 110 where the residual liquid 131' remains. The residual liquid 131' contains components of the first reagent 131, which may affect the second reagent 132 (or subsequent processes using the second reagent 132) and may prevent the analysis from being performed correctly.

[0027] Figure 2B This is a schematic diagram illustrating the steps of preparing the mixture using the automatic analysis apparatus 100 of Embodiment 1. In Embodiment 1, after the reagent introduction mechanism 120 draws out the first mixture prepared from the first reagent 131 from the mixing chamber 110, a buffer reagent 133 is introduced into the mixing chamber 110 before the second reagent 132 is introduced. The buffer reagent 133 is a reagent capable of mitigating the impact of residual liquid 131' (i.e., residual components of the first reagent 131) on the second reagent 132 (or subsequent processes using the second reagent 132).

[0028] By introducing buffer reagent 133, even if residual liquid 131' remains in the mixing chamber 110, its impact can be mitigated, and subsequent processes can be carried out correctly. This solves the problem of... Figure 2A The problem caused by residual liquid 131' in the conventional mixture preparation process is shown.

[0029] When the buffer reagent 133 is introduced into the mixing chamber 110, the control unit 161 needs to know the characteristics of the residual liquid 131'. That is, it needs to know in advance the component characteristics of the residual liquid 131' that affect the second reagent 132 (or subsequent steps such as the step of reacting the second reagent 132 with the sample). Specifically, the pH value and molecular polarity of the residual liquid 131' are the aforementioned component characteristics. These characteristics of the residual liquid 131' can be described in advance as characteristics of the first reagent 131 in data, and this data is pre-stored in the storage unit 162. The control unit 161 can know the characteristics of the residual liquid 131' based on this data.

[0030] When the pH of the residual solution 131' is moderated by buffer reagent 133, buffer reagent 133 only needs to have a pH value with the opposite polarity to that of the residual solution 131'. That is, if the first reagent 131 is acidic, then buffer reagent 133 can be alkaline, and if the first reagent 131 is alkaline, then buffer reagent 133 can be acidic.

[0031] When the molecular polarity of the residual liquid 131' is mitigated by buffer reagent 133, a reagent capable of diluting the molecular polarity of the residual liquid 131' can be used as buffer reagent 133. For example, if the first reagent 131 is an organic solvent, pure water can be used as buffer reagent 133. Other suitable diluents can also be used. That is, if the molecular polarity of the first reagent 131 is high, a reagent with relatively low molecular polarity can be used as buffer reagent 133, and if the molecular polarity of the first reagent 131 is low, a reagent with relatively high molecular polarity can be used as buffer reagent 133.

[0032] When introducing buffer reagent 133 into mixing chamber 110, control unit 161 needs to determine the amount of residual liquid 131'. Because the amount of residual liquid 131' varies, the amount of buffer reagent 133 also varies. The amount of residual liquid 131' can typically be defined as the dead volume in mixing chamber 110. Dead volume is the amount of liquid that inevitably remains in mixing chamber 110 because the reagent introduction mechanism 120 cannot completely draw the reagent from the mixing chamber 110. Dead volume can be calculated based on the shape of mixing chamber 110 and the shape of reagent introduction mechanism 120 (specifically, nozzle shape). Data describing dead volume can be pre-stored in storage unit 162. Therefore, control unit 161 can determine the dead volume based on this data, eliminating the need for calculation each time.

[0033] If only a portion of the components in residue 131' will affect subsequent processes using the second reagent 132, the proportion of that component in residue 131' needs to be determined in advance. This proportion can be determined based on the proportions of the various reagents used in preparing the first mixture. For example, this proportion can be described in the data describing the dead zone volume.

[0034] Figure 3 An example illustrating the volume of buffer reagent 133 is shown. Here, the following examples are used as the first reagent 131: (a) for the step of analyzing sample A (cycle 1), a mixture of pure water and organic solvent = 0:100 [μL] is provided as the first mixture; (b) for the step of analyzing sample B (cycle 2), a mixture of pure water and organic solvent = 20:80 [μL] is provided as the second mixture. In these examples, the organic solvent in cycle 1 corresponds to the first reagent 131, and the organic solvent in cycle 2 corresponds to the second reagent 132.

[0035] After cycle 1, it is assumed that 10 μL of organic solvent remains in the mixing chamber 110 as residual liquid 131'. In cycle 2, a mixture needs to be prepared with a ratio of pure water: organic solvent = 20:80 = 1:4, therefore, it is necessary to maintain this ratio by mitigating the influence of residual liquid 131'. Therefore, in cycle 2, 2.5 μL of pure water is introduced as buffer reagent 133. Thus, the ratio of pure water: organic solvent (residual liquid 131') is 1:4, so even if a mixture of pure water: organic solvent = 20:80 [μL] is further supplied as a second reagent 132, the ratio of pure water: organic solvent = 1:4 can be maintained. Therefore, the influence of residual liquid 131' can be mitigated.

[0036] When neutralizing the pH of the residual solution 131' using the pH of buffer reagent 133, the volume of buffer reagent 133 is determined to maintain the amount of either acidic or alkaline solvent in the second reagent 132. For example, if the second reagent 132 contains neither acidic nor alkaline solvent, then buffer reagent 133 sufficient to completely neutralize the pH of the residual solution 131' is introduced. For example, if the residual solution 131' has a pH of 6.0 and a volume of 10 μL, then buffer reagent 133 should have a pH of 8.0 and a volume of 10 μL.

[0037] Control unit 161 mitigates the impact of residual liquid 131' when using the second reagent 132 through the above steps. Then, control unit 161 analyzes the sample by reacting the second reagent 132 with the sample and obtains the results. For example, the spectral values ​​of the components contained in the sample can be obtained as the analysis results. If the spectral area of ​​the sample component converges within the allowable range (assuming the amount of component in the sample), control unit 161 determines that buffer reagent 133 has adequately mitigated the impact of residual liquid 131'. If it does not converge within the allowable range, it determines that buffer reagent 133 has failed to adequately mitigate the impact of residual liquid 131' and outputs an alarm indicating this. The spectral area of ​​the components of the internal standard substance can be used instead of the spectral area of ​​the sample component, or used together with the spectral area of ​​the sample component. Alternatively, the spectral peak can be used instead of the spectral area. The same applies in the following embodiments.

[0038] <Implementation Method 1: Summary>

[0039] In the automatic analysis apparatus 100 of this embodiment 1, after the first reagent 131 is discharged from the mixing chamber 110 and before the second reagent 132 is introduced into the mixing chamber 110, a buffer reagent 133 for mitigating the influence of the first reagent 131 is introduced into the mixing chamber 110. This reduces the influence of the residual liquid 131', allowing subsequent processes such as analysis using the second reagent 132 to be performed appropriately.

[0040] <Implementation Method 2>

[0041] Figure 4 This diagram illustrates the steps for preparing the mixture in Embodiment 2 of this disclosure. In Embodiment 1, an example is shown where, after the first reagent 131 is discharged from the mixing chamber 110, a buffer reagent 133 is introduced into the mixing chamber 110, followed by the introduction of a second reagent 132 into the mixing chamber 110. In this Embodiment 2, after the first reagent 131 is discharged from the mixing chamber 110, the same component as the buffer reagent 133 is pre-mixed into the second reagent 132, and then the second reagent 132 is introduced into the mixing chamber 110. This shortens the step of introducing the buffer reagent 133 into the mixing chamber 110. Other structures are the same as in Embodiment 1.

[0042] <Implementation Method 3>

[0043] Figure 5 An example illustrating the volume of buffer reagent 133 is shown. The first reagent 131 and the second reagent 132 sometimes possess multiple characteristics that affect the sample analysis process. Figure 5 In this process, two characteristics—(a) the molecular polarity of the organic solvent and (b) the pH values ​​of the acidic and basic solvents—each have an impact. The amounts of the components constituting buffer reagent 133 are determined according to each of these impacting characteristics, and they are added together to form the final buffer reagent 133.

[0044] exist Figure 5 In the example shown, the second reagent 132 in cycle 2 is a mixture obtained by mixing pure water and organic solvent in a ratio of 20:80 [μL]. Since 9 μL of pure water remains as the residual liquid 131', 36 μL of organic solvent is used as the buffer reagent 133. Thus, since the ratio of pure water to organic solvent is 9:36 = 1:4, the ratio of these reagents in the second reagent 132 can be maintained.

[0045] Sometimes, only one of the acidic or basic solvents is used to form the mixture. In this case, the mixture contains only one of the acidic or basic solvents, and may contain components other than those solvents as needed. Figure 5 In the example shown, it is assumed that the second reagent 132 in cycle 2 contains 0 μL of both acidic and alkaline solvents (i.e., neutral). Since 1 μL of acidic solvent remains as residual liquid 131', 1 μL of alkaline solvent is used as buffer reagent 133. Therefore, the pH values ​​of both the acidic and alkaline solvents in cycle 2 are substantially neutral, thus maintaining the pH values ​​of these solvents in the second reagent 132 as intended. That is, the control unit 161 selects the characteristics and volume of the buffer reagent 133 that can pre-neutralize the residual liquid 131', ensuring that the pH values ​​of the acidic and alkaline solvents in the second reagent 132 do not change when the second reagent 132 is introduced into the mixing chamber 110.

[0046] <Implementation Method 4>

[0047] Figure 6 This is an example of a user interface provided by the control unit 161. This user interface displays the reagent amount in each analysis cycle and provides information indicating whether the buffer reagent 133 has adequately mitigated the effect of the first reagent 131. The criteria for determining whether the effect has been adequately mitigated are as described in Embodiment 1.

[0048] exist Figure 6In loop 2 shown, an alarm indicating this meaning is triggered because a region where the spectral area of ​​the sample component did not converge within the allowable range was detected. For example, control unit 161 can describe... Figure 6 The data shown above is output to the storage unit 162. The controller 161 can also provide services such as outputting this data to devices like a display. Figure 6 The user interface shown. Additionally, as... Figure 6 The underlined section at the bottom indicates which part of the component spectrum is outside the allowed range, which can be displayed on the user interface. Figure 6 In the example shown below, it can be inferred that the component in the first reagent 131, which would affect the component corresponding to the slashed portion, was not adequately buffered.

[0049] The user interface can be provided by a device other than the automatic analysis device 100. For example, the control unit 161 can describe... Figure 6 The data showing the content is stored in the storage unit 162, and other devices can read the data to provide prompts, such as... Figure 6 The user interface shown.

[0050] <Variations on this disclosure>

[0051] This disclosure is not limited to the embodiments described above, and includes various modifications. For example, the above-described embodiments are detailed for ease of understanding and illustration of the invention, and the invention is not necessarily limited to including all the structures described. Furthermore, a portion of one embodiment may be replaced with a structure from another embodiment. Additionally, structures from other embodiments may be incorporated into the structure of one embodiment. Furthermore, for a portion of the structure of each embodiment, a portion of the structure from another embodiment may be added, deleted, or replaced.

[0052] In the above implementation, for example, in a certain loop, it can be as follows: Figure 2B As described, buffer reagent 133 is introduced between the first reagent 131 and the second reagent 132, while in another cycle, as... Figure 4 As described, the second reagent 132 and the buffer reagent 133 are introduced together.

[0053] In the above embodiments, the mixture in the mixing chamber 110 can be stirred by a stirrer. For example, it can function as a stirrer by vibrating the entire plate in which the mixing chamber 110 is placed.

[0054] In the above embodiments, the characteristics of the residual liquid 131' and the buffer reagent 133 do not have to be completely opposite. For example, even if the pH of the residual liquid 131' is 6.0 and the pH of the buffer reagent 133 is 7.5, the pH of the residual liquid 131' can be neutralized as long as the volume of the buffer reagent 133 is twice the volume of the residual liquid 131'. Furthermore, even if complete neutralization is not possible, it is sufficient if the pH can be buffered to a level where it has no effect in subsequent steps using the second reagent 132. The same applies to other characteristics of the residual liquid 131', such as its molecular polarity.

[0055] In the above embodiments, the first reagent 131 and the second reagent 132 can be configured to achieve the optimal component ratio in each sample analysis step. For example, if a reagent with pH=8.0 (alkaline) is required in the analysis step of sample A, the first reagent 131 can be made with a stronger alkaline solution, and the analysis step can be performed after neutralizing the pH value in a subsequent step.

[0056] In the above embodiments, examples of reagents constituting the mixture may include ACN (acetonitrile), MeOH (methanol), and appropriate acidic or alkaline buffer solutions.

[0057] In the above embodiments, pH value and molecular polarity are used as examples of characteristics that affect the subsequent processes of the residual liquid 131'. However, for other characteristics that affect the subsequent processes, a reagent that can mitigate the effect can also be used as a buffer reagent 133.

[0058] Label Explanation

[0059] 100: Automatic Analysis Device

[0060] 110: Mixing chamber

[0061] 120: Reagent delivery mechanism

[0062] 130: Reagent container

[0063] 140: Mixture dispensing mechanism

[0064] 150: Reaction vessel

[0065] 161: Control Department

[0066] 162: Storage Department.

Claims

1. An automatic analysis device that analyzes a sample using a reagent, characterized by comprising: include: A mixing chamber for preparing a mixture by mixing the reagent with other liquids; as well as The reagent introduction mechanism introduces the reagent into the mixing chamber. A control unit that controls the reagent introduction mechanism; as well as The storage unit stores data describing the properties of the first reagent. The reagent introduction mechanism introduces the first reagent into the mixing chamber to prepare the first mixture. After the first mixture is discharged from the mixing chamber, the reagent introduction mechanism introduces a second reagent into the mixing chamber to prepare a second mixture. The control unit Based on the characteristics of the first reagent described in the data, a reagent for mitigating the effect of the first reagent remaining in the mixing chamber during the preparation of the second mixture is determined, and this determined reagent is used as a buffer reagent. The reagent introduction mechanism is then controlled to introduce the buffer reagent into the mixing chamber. The amount of buffer reagent is determined based on the amount of the first reagent remaining in the mixing chamber after the action of discharging the first mixture from the mixing chamber is performed.

2. The automatic analysis device as described in claim 1, characterized in that, After the first mixture is discharged from the mixing chamber, the reagent introduction mechanism introduces the buffer reagent into the mixing chamber before introducing the second reagent into the mixing chamber.

3. The automatic analysis device as described in claim 1, characterized in that, The reagent introduction mechanism introduces the buffer reagent into the mixing chamber as at least a part of the second reagent.

4. The automatic analysis device as described in claim 1, characterized in that, The reagent delivery mechanism determines the characteristics and amount of the buffer reagent, such that by mitigating the effects of the first reagent, the characteristics of the second mixture required in the analytical process using the second mixture can be ensured.

5. The automatic analysis device as described in claim 1, characterized in that, The first reagent has the characteristic of pH value as the first reagent. The reagent delivery mechanism uses a buffer reagent with a pH value that can neutralize the pH value of the first reagent.

6. The automatic analysis device as described in claim 1, characterized in that, The first reagent has the characteristic of molecular polarity. The reagent delivery mechanism uses a reagent with molecular polarity capable of diluting the molecular polarity of the first reagent as the buffer reagent.

7. The automatic analysis device as described in claim 1, characterized in that, The first reagent has a first pH value and a first molecular polarity. The reagent delivery mechanism uses a mixed reagent as the buffer reagent, which is obtained by mixing a reagent having a second pH value capable of neutralizing the first pH value and a reagent having a second molecular polarity capable of diluting the first molecular polarity.

8. The automatic analysis device as described in claim 1, characterized in that, The second reagent is a reagent containing at least one of an acidic solvent or a basic solvent. The reagent introduction mechanism selects the following reagent as the buffer reagent, which neutralizes the first reagent remaining in the mixing chamber after the action of discharging the first mixture from the mixing chamber, thereby ensuring that the pH value of the acidic solvent and the pH value of the alkaline solvent contained in the second reagent during the preparation of the second mixture are not changed due to the first reagent remaining in the mixing chamber.

9. The automatic analysis device as described in claim 1, characterized in that, The second reagent is obtained by mixing organic and non-organic solvents in a specified ratio. The reagent introduction mechanism selects the buffer reagent based on the respective amounts of the organic solvent and the non-organic solvent remaining in the mixing chamber after the action of discharging the first mixture from the mixing chamber, such that the ratio of the organic solvent and the non-organic solvent present in the mixing chamber during the preparation of the second mixture is the predetermined ratio.

10. The automatic analysis device as described in claim 1, characterized in that, The automatic analysis device outputs information indicating whether the influence of the first reagent in the preparation of the second mixture has been mitigated to an acceptable level, based on whether the spectral peak or spectral area of ​​the components contained in the sample or the components contained in the internal standard material analyzed together with the sample converges within an acceptable range.

11. The automatic analysis device as described in claim 10, characterized in that, If the influence of the first reagent is not mitigated to an acceptable level during the preparation of the second mixture, the automatic analysis device outputs an alarm indicating this.

12. The automatic analysis device as described in claim 10, characterized in that, The automated analysis device performs the process of analyzing the sample using the mixture multiple times. For processes in which the effect of the first reagent remaining in the mixing chamber is not mitigated to an acceptable level during repeated implementations, the automated analysis device adds a label to the data describing the process results that expresses this meaning.

13. The automatic analysis device as described in claim 10, characterized in that, The automated analysis device includes a user interface for displaying the information.

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