Quality analysis device

The mass spectrometer addresses contamination in the reagent refrigerator by using an inert gas supply system to reduce oxygen concentration and prevent condensation, thereby maintaining a clean and sterile reagent storage environment.

JP7886426B2Active Publication Date: 2026-07-07HITACHI HIGH TECH CORP

Patent Information

Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
HITACHI HIGH TECH CORP
Filing Date
2023-11-16
Publication Date
2026-07-07

AI Technical Summary

Technical Problem

Existing mass spectrometers face contamination issues within the reagent refrigerator due to the ingress of outside air during reagent replacement, leading to condensation and potential mold or bacterial growth.

Method used

A mass spectrometer design that incorporates an inert gas supply system, branching into separate paths for the mass spectrometry unit and reagent refrigerator, using nitrogen gas to maintain cleanliness by reducing oxygen concentration and preventing contamination.

Benefits of technology

The inert gas system effectively maintains the reagent refrigerator's cleanliness, preventing condensation and microbial growth, ensuring a sterile environment for reagents.

✦ Generated by Eureka AI based on patent content.

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Patent Text Reader

Abstract

This mass spectrometer comprises: a reagent refrigerator 21 that stores a reagent container; a mass spectrometry unit 40 that conducts mass spectrometry on a specimen that has been pretreated by reaction with a reagent stored in the reagent container; and gas piping 71 that is connected to a gas source 50 to supply an inert gas from the gas source. The gas piping branches off into: a first inert gas flow path for supplying inert gas to the mass spectrometry unit; and a second inert gas flow path for supplying inert gas to the reagent refrigerator. This configuration makes it possible to keep the inside of the reagent refrigerator clean.
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Description

Technical Field

[0001] The present invention relates to a mass spectrometer.

Background Art

[0002] Patent Document 1 discloses an automatic analyzer that keeps the inside of a reagent cooler where reagent containers are stored clean. When outside air flows into a reagent cooler that stores reagent containers containing analysis reagents at a low temperature for a long time, it may cause contamination inside the reagent cooler due to the intrusion of dust, miscellaneous bacteria, etc. contained in the outside air and condensation due to the temperature difference between the inside and outside of the reagent cooler. Therefore, when the reagent container replacement part for replacing the reagent container is open, the inside of the reagent cooler is made positive pressure with respect to the surroundings of the reagent cooler, or the contamination of the reagent cooler is suppressed by removing dust or miscellaneous bacteria adhering to the reagent container.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0004] In Patent Document 1, when replacing the reagent container, the inside of the reagent cooler is made positive pressure to suppress the inflow of normal-temperature air, thereby suppressing the occurrence of condensation inside the reagent cooler. However, during reagent replacement, the reagent cooler opens wide, and due to the agitation of the air inside the reagent cooler accompanying the operation of the mechanism for reagent replacement, it is inevitable that a certain amount of outside air will flow in.

[0005] A mass spectrometer is a device that ionizes a liquid sample, introduces it into a vacuum chamber, and separates the ions according to their mass-to-charge ratio (m / z). When a mass spectrometer generates ions using, for example, electrospray ionization (ESI), a heated inert gas (e.g., nitrogen gas) is sprayed onto the sample droplets. Therefore, an inert gas is introduced into the mass spectrometer from a gas source.

[0006] Therefore, the inventors considered using an inert gas from a gas source to keep the inside of the reagent refrigerator clean. The object of the present invention is to provide a mass spectrometer capable of keeping the inside of the reagent refrigerator clean using an inert gas. [Means for solving the problem]

[0007] A mass spectrometer according to one embodiment of the present invention comprises a reagent refrigerator for storing reagent containers, a mass spectrometry unit for performing mass analysis on a sample that has been pre-treated by reacting with reagents contained in the reagent containers, and a gas pipe connected to a gas source for supplying inert gas from the gas source. The gas pipe is branched into a first inert gas passage for supplying inert gas to the mass spectrometry unit and a second inert gas passage for supplying inert gas to the reagent refrigerator. [Effects of the Invention]

[0008] This invention provides a mass spectrometer capable of maintaining cleanliness inside a reagent refrigerator using an inert gas. Other challenges and novel features will become apparent from the description and accompanying drawings herein. [Brief explanation of the drawing]

[0009] [Figure 1] This is an example of a mass spectrometer configuration. [Figure 2] This is a diagram showing the configuration of the inert gas flow path in a mass spectrometer. [Figure 3] This is a diagram showing the configuration of the cooling water channel and inert gas channel in a reagent refrigerator. [Modes for carrying out the invention]

[0010] The embodiments of the present invention will be described below with reference to the drawings.

[0011] Figure 1 shows an example of the configuration of the mass spectrometer 1 in this embodiment. The mass spectrometer 1 mainly consists of a sample input unit 10, a pre-processing unit 20, a separation unit 30, and a mass spectrometry unit 40. The sample to be analyzed is contained in a sample container, which is mounted on a sample rack 16 and then fed into the mass spectrometer 1 from the sample input unit 10.

[0012] The sample input unit 10 includes a sample loading / unloading unit 11 and a buffer unit 14. Sample racks 16 loaded into the sample loading / unloading unit 11 are transported to the pre-processing unit 20 by a rack transport mechanism 12. In the pre-processing unit 20, the sample racks 16 are transported to a rack transport mechanism 15, and at the dispensing position on the rack transport mechanism 15, the required amount of sample is dispensed from the sample containers into the reaction vessel on the incubator 23. Once dispensing to all the samples contained in the multiple sample containers loaded on the sample rack 16 is completed, the sample rack 16 is transported from the rack transport mechanism 15 to a rack transport mechanism 13, returned to the sample loading / unloading unit 11 by the rack transport mechanism 13, and then collected by the operator. The buffer unit 14 is used to temporarily move the sample racks 16 to the rack transport mechanism 12 to prevent them from accumulating on the rack transport mechanism 12 when there are too many sample racks 16 loaded into the sample loading / unloading unit 11 and the analysis processing of the device 1 cannot keep up. In the example shown in Figure 1, a belt conveyor type conveying mechanism is used as an example of a rack transport mechanism, but the system is not limited to this method.

[0013] The pre-processing unit 20 is a unit that performs pre-processing for mass spectrometry. The content of the pre-processing is not limited. For example, the pre-processing unit 20 performs processing to amplify the analyte in the sample. The pre-processing unit 20 includes a reagent refrigerator 21 for storing reagents necessary for pre-processing, an incubator 23 for maintaining a constant temperature of the reagent-sample mixture to promote the reaction, a reaction vessel supply mechanism 24 for storing reaction vessels for mixing reagents and samples and supplying reaction vessels to the incubator 23, a reagent dispensing mechanism 25 for dispensing reagents from reagent containers stored in the reagent refrigerator 21 to the reaction vessels on the incubator 23, a sample dispensing mechanism 26 for dispensing samples from sample containers on the sample rack 16 to the reaction vessels on the incubator 23, and a sample extraction unit 27 for removing components unnecessary for subsequent analysis from the reaction solution of reagents and samples after the reaction in the incubator 23 has finished.

[0014] The separation unit 30 is a unit that separates the sample, which has been pre-treated in the pre-treatment unit 20, into multiple components, and the mass spectrometry unit 40 is a unit (mass spectrometer) that performs mass spectrometry on the multiple components separated by the separation unit 30. The analytical method that uses a liquid chromatograph as the separation unit 30 and a mass spectrometer as the detector of the liquid chromatograph is known as liquid chromatography-mass spectrometry (LC-MS).

[0015] The structure of the reagent refrigerator 21 will be briefly explained using Figures 1 and 3. Figure 3 shows a cross-sectional view of the reagent refrigerator 21. Cooling water is supplied to the reagent refrigerator 21 to maintain a low temperature inside. A lid 28 is fixed to the reagent refrigerator 21, and the lid 28 is provided with a reagent exchange mechanism 22 and a dispensing port 29. Although not shown, a reagent disc for holding reagents is rotatably provided inside the reagent refrigerator 21. The reagent exchange mechanism 22 is normally isolated from the reagent refrigerator 21 to prevent outside air from flowing into it. However, when exchanging reagents, reagents are added to and removed from the reagent disc inside the refrigerator through the opening 22o, and at this time, outside air flows into the reagent refrigerator 21. Also, since the reagent dispensing mechanism 25 dispenses reagents from the reagent container, the dispensing port 29 for passing the probe through is always open, although its opening area is small.

[0016] As described above, it is difficult to keep the inside of the reagent refrigerator 21 completely isolated from the outside air. Therefore, if condensation occurs inside the reagent refrigerator 21, there is a risk of mold and bacteria growing. In this embodiment, we focused on the fact that the mass spectrometer 1 is supplied with inert gas from the gas source 50, and by supplying the inert gas from the gas source 50, which does not contain oxygen like the outside air, not only to the mass spectrometry unit 40 but also to the reagent refrigerator 21, we have created a configuration that keeps the inside of the reagent refrigerator clean.

[0017] Figure 2 shows a diagram of the inert gas flow path of the mass spectrometer 1. The boundary line 60, indicated by a dashed line, conceptually represents the boundary between the mass spectrometer 1 and an external device. The gas source 50 may be a gas generator that produces inert gas, or a cylinder that stores inert gas. Here, nitrogen gas will be used as the inert gas. The gas source 50 is connected to the gas piping 71 via a connection part 62. Here, the gas piping 71 will be described by dividing it into three sections A to C. Note that the flow path configuration shown in Figure 2 is just one example and is not limited to this flow path configuration.

[0018] Section A is connected to the gas source 50 via the connection part 62 and is branched into two, with the branched gas pipes leading to regulators 54a and 54b, respectively. The gas pipe 71 in section A is denoted as gas pipe 71A. A filter 51 and a pressure sensor 52 are provided in gas pipe 71A from upstream. The filter 51 is provided to protect the mechanism supplying inert gas by capturing dust and particulate matter if they are mixed in with the gas supplied to gas pipe 71. The pressure sensor 52 is provided to monitor the pressure of the inert gas supplied from the gas source 50. Downstream of the pressure sensor 52, gas pipe 71A is branched, with one channel connected to the regulator 54a for the mass spectrometry unit and the other channel connected to the regulator 54b for the reagent refrigerator. Manual valves 53a and 53b are provided in the branched channels, respectively. These are used when it is desired to stop the supply of inert gas to the mass spectrometry unit 40 or the reagent refrigerator 21 during equipment maintenance.

[0019] Section B is the section from regulator 54a to mass spectrometer 40. The gas pipe 71 in section B is denoted as gas pipe 71B. Regulator 54a is provided to reduce the gas pressure of the inert gas compared to section A and supply the inert gas to mass spectrometer 40 at a stable gas pressure. The inert gas supplied to mass spectrometer 40 is, for example, exhausted by vacuum pump 55 after being used for ionization of the sample, and is processed by exhaust equipment 65 connected via connection part 63.

[0020] Section C is the section from regulator 54b to reagent cooler 21. The gas pipe 71 in section C is denoted as gas pipe 71C. Regulator 54b is provided to reduce the gas pressure of the inert gas compared to section A and supply the inert gas to reagent cooler 21 at a stable gas pressure. The gas pressure in section C may be lower than the gas pressure in section B. A needle valve 56, a flow meter 57, and a gas cooler 58 are provided in gas pipe 71C from upstream. Needle valve 56 is provided to adjust the flow rate of the inert gas supplied to reagent cooler 21. Flow meter 57 is provided to monitor the flow rate of the inert gas supplied to reagent cooler 21. Gas cooler 58 is provided to cool the inert gas supplied to reagent cooler 21. The configuration for cooling the inert gas will be described using FIG. 3.

[0021] The inert gas supplied to reagent cooler 21 leaks out from the opening of reagent cooler 21. Therefore, by providing an exhaust fan 59 on the exterior cover 61 of the device, the inert gas leaking out from the opening of reagent cooler 21 is exhausted and processed by exhaust equipment 65 connected via connection part 64.

[0022] FIG. 3 is a configuration diagram of a cooling water flow path and an inert gas flow path in the reagent cold storage 21. The inert gas flow path is the one shown in FIG. 2, but is shown in a simplified manner here. In this embodiment, by supplying an inert gas to the reagent cold storage 21 to reduce the oxygen concentration inside the reagent cold storage 21, the generation of contamination inside the storage is suppressed. For this purpose, it is effective to reduce the oxygen concentration near the bottom surface of the reagent cold storage 21 where dew condensation tends to accumulate. However, when nitrogen gas is used as the inert gas, the specific gravity of nitrogen gas is 0.967 (air = 1), and the gas density does not differ much from that of air. Therefore, in this embodiment, the nitrogen gas is cooled to increase the gas density so that the nitrogen gas tends to stay near the bottom surface of the reagent cold storage 21.

[0023] To cool the inside of the reagent cold storage 21, a water-cooled chiller 76 and a cooling water pipe 75 for circulating cooling water between the water-cooled chiller 76 and the reagent cold storage 21 are provided. This cooling water flow path is used for cooling the nitrogen gas. In the cooling water flow path for supplying cooling water from the water-cooled chiller 76 to the reagent cold storage 21, a gas cooler 58 is connected to the cooling water pipe 75, and by passing a gas pipe 71 through the gas cooler 58, the nitrogen gas is cooled. By arranging the gas cooler 58 upstream of the cooling water flow path from the reagent cold storage 21, nitrogen gas at a temperature lower than that of the reagent cold storage 21 can be supplied. Also, it is desirable to connect the gas pipe 71 at the bottom surface of the reagent cold storage 21 so that the nitrogen gas tends to stay near the bottom surface of the reagent cold storage 21. The inert gas may be supplied from a plurality of locations on the bottom surface of the reagent cold storage 21.

[0024] The present invention is not limited to the above-described embodiments and includes various modifications. For example, the above-described embodiments have been described in detail for easy understanding of the present invention and are not necessarily limited to those having all the configurations described. Also, it is possible to add, delete, or replace a part of the configuration of the embodiment with another configuration.

Explanation of Reference Numerals

[0025] 1: Mass spectrometer, 10: Sample input unit, 11: Sample loading / unloading unit, 12, 13, 15: Rack transport mechanism, 14: Buffer unit, 20: Pre-processing unit, 21: Reagent refrigerator, 22: Reagent exchange mechanism, 22o: Opening, 23: Incubator, 24: Reaction vessel supply mechanism, 25: Reagent dispensing mechanism, 26: Sample dispensing mechanism, 27: Sample extraction unit, 28: Lid, 29: Dispensing port, 30: Separation unit, 40: Mass spectrometry unit, 50: Gas source, 51: Filter, 52: Pressure sensor, 53: Manual valve, 54: Regulator, 55: Vacuum pump, 56: Needle valve, 57: Flow meter, 58: Gas cooler, 59: Exhaust fan, 60: Boundary line, 61: Outer cover, 62, 63, 64: Connection unit, 65: Exhaust equipment, 71: Gas piping, 75: Cooling water piping, 76: Water chiller.

Claims

1. A reagent refrigerator for storing reagent containers, A mass spectrometry unit that performs mass spectrometry on a sample that has been pre-treated by reacting it with the reagent contained in the reagent container, It has a gas pipe connected to a gas source and supplied with inert gas from the gas source, The gas piping of the mass spectrometer is branched into a first inert gas passage for supplying the inert gas to the mass spectrometer and a second inert gas passage for supplying the inert gas to the reagent refrigerator.

2. In claim 1, A water-cooled chiller for cooling the aforementioned reagent storage cabinet, A cooling water pipe for circulating cooling water between the water-cooled chiller and the reagent refrigerator, A mass spectrometer comprising a gas cooler arranged in a cooling water channel that supplies the cooling water to the reagent refrigerator, and which cools the inert gas.

3. In claim 2, The gas cooler is a mass spectrometer that cools the inert gas passing through the gas piping constituting the second inert gas flow path with the cooling water.

4. In claim 1, A mass spectrometer in which the gas piping constituting the second inert gas flow path is connected to the bottom surface of the reagent refrigerator.

5. In claim 1, A first regulator is connected to the first inert gas flow path, and the inert gas is supplied at a pressure lower than the gas pressure supplied from the gas source. A second regulator is connected to the second inert gas flow path, and the inert gas is supplied at a pressure lower than the gas pressure supplied from the gas source. A mass spectrometer in which the gas pressure in the second inert gas flow path is lower than the gas pressure in the first inert gas flow path.

6. In claim 5, A mass spectrometer comprising a pressure sensor for measuring the gas pressure of the inert gas supplied from the gas source, positioned upstream of the branching point between the first inert gas flow path and the second inert gas flow path in the gas piping.

7. In claim 5, A first valve capable of shutting off the supply of the inert gas to the mass spectrometry unit is provided in the first inert gas flow path. A mass spectrometer in which a second valve capable of shutting off the supply of the inert gas to the reagent refrigerator is arranged in the second inert gas flow path.

8. In claim 1, The inert gas supplied to the mass spectrometry unit is exhausted by a vacuum pump connected to the mass spectrometry unit. The inert gas supplied to the reagent refrigerator is exhausted by an exhaust fan provided on the outer cover. The exhausted inert gas is processed by an exhaust system in a mass spectrometer.

9. In claim 1, The mass spectrometry unit uses the inert gas to ionize the sample, The aforementioned inert gas is nitrogen gas in the mass spectrometer.