Mass spectrometer

Abstract

The present invention can provide a compact mass spectrometer with improved maintainability. The mass analysis unit (40) has a first housing (206) and a second housing (208) disposed below the first housing, and an ionization unit (201), a mass analysis unit (202) provided with a quadrupole mass filter, a mass detection unit (203), and an RF output unit (205) provided with a resonance circuit (108) for applying a high-frequency voltage to the quadrupole mass filter are disposed in the first housing. The second housing is provided with a substrate housing unit (204) that houses at least a control circuit substrate that includes an RF control circuit (101) that generates a high-frequency signal, and an RF substrate that includes an RF amplifier (107) that amplifies the high-frequency signal and supplies the amplified high-frequency signal to the resonance circuit. An ionization unit, a mass analysis unit, and a mass detection unit are disposed in the first housing from the front surface toward the rear surface, and a substrate storage unit is disposed in the front surface in the second housing.

Description

Technical Field

[0001] The present invention relates to a mass analysis device. Background Art

[0002] A mass spectrometer is a device that determines the sample to be analyzed by ionizing the sample to be analyzed and analyzing the mass of the generated ions. Due to its high measurement accuracy, it has also been used in clinical examinations, pharmaceutical research and other fields in recent years. The mass spectrometer has a mass analysis unit based on mass separation of ions. Although there are multiple methods based on mass separation of ions, the method using a quadrupole shown in Patent Document 1 is a representative method. The mass analysis unit includes two sets of electrodes (quadrupole electrodes) facing each other, and a high-frequency electric field is formed inside the quadrupole electrode by applying a high-frequency voltage to the quadrupole electrodes. The ions of the sample to be analyzed move toward the detection unit while vibrating in the high-frequency electric field. Prior art literature Patent Literature

[0003] Patent Document 1: Japanese Patent Application Laid-Open No. 10-112282 Summary of the Invention Technical problem to be solved by the invention

[0004] In order to process multiple samples at high throughput, a mass spectrometer is preferably compact and capable of performing a series of operations, including pre-processing the sample loaded into the device, separating the components of the sample to be analyzed, and continuously performing mass analysis. Therefore, the device is constructed by modularizing and combining these functions. As a result, the mechanisms that the operator can access daily during analysis and maintenance need to be located on the front surface of the mass spectrometer, rather than on the side or back where they are integrated with other modules.

[0005] On the other hand, the accuracy of the high-frequency voltage applied to a quadrupole mass spectrometer (referred to herein as a quadrupole mass filter) affects the accuracy of the measurement of detected ions. Therefore, feedback control of the applied high-frequency voltage is performed. The control unit and the controlled unit performing the feedback control are preferably arranged as close together as possible. If this is not possible, the accuracy of the feedback control may be reduced due to the influence of noise generated during communication between the control unit and the controlled unit. Technical solutions to technical problems

[0006] A mass spectrometer according to one embodiment of the present invention is a mass spectrometer including a mass spectrometer section, the mass spectrometer section having a first frame and a second frame arranged below the first frame, wherein the first frame comprises an ionization unit for ionizing an analysis target sample, a mass spectrometer having a quadrupole mass filter for introducing ions from the ionization unit and allowing ions of a specified mass-to-charge ratio (m / z) to pass therethrough, a mass detection unit for detecting ions after passing through the mass spectrometer, and an RF output unit having a resonant circuit for applying a DC voltage and a high-frequency voltage to the quadrupole mass filter in a superimposed manner, and the second frame comprises a substrate storage unit for storing at least a control circuit substrate including an RF control circuit for generating a high-frequency signal and an RF substrate including an RF amplifier for amplifying the high-frequency signal and supplying it to the resonant circuit, wherein the ionization unit, the mass spectrometer, and the mass detection unit are arranged from the front surface toward the rear surface of the first frame, and the substrate storage unit is arranged on the front surface of the second frame. Effects of the Invention

[0007] A mass analyzer is provided that is compact and has improved maintainability. Other problems and novel features will become apparent from the description of this specification and the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1 This is an example of the structure of a mass spectrometer. Figure 2 This is an example of the arrangement of units constituting the mass analysis unit. Figure 3A This is a diagram for explaining the structure of a quadrupole mass filter. Figure 3B This is a diagram for explaining the structure of a quadrupole mass filter. Figure 4 This is an example of the configuration of a power supply circuit for a quadrupole mass filter. Figure 5 This is the control circuit for the RF voltage applied to the quadrupole mass filter. Figure 6 1 is a diagram showing a first feedback method for RF voltage control. Figure 7 2 is a diagram showing a second feedback method for RF voltage control. Figure 8 This is a diagram showing a third feedback method for RF voltage control. DETAILED DESCRIPTION

[0009] Figure 1The following shows an example configuration of an automatic analyzer 1 according to this embodiment. The mass analyzer 1 primarily comprises a sample input section 10, a pretreatment section 20, a separation section 30, and a mass analyzer 40. The sample to be analyzed is contained in a sample container, which is mounted on a sample holder 16 and then introduced into the mass analyzer 1 from the sample input section 10.

[0010] The sample input section 10 includes a sample loading and unloading section 11 and a buffer section 14. The sample rack 16 loaded into the sample loading and unloading section 11 is unloaded to the pretreatment section 20 by the rack conveying mechanism 12. In the pretreatment section 20, the sample rack 16 is transferred to the rack conveying mechanism 15, and at the dispensing position on the rack conveying mechanism 15, the necessary amount of sample is dispensed from the sample container to the reaction container on the incubator 23. When the dispensing of the samples contained in the multiple sample containers carried on the sample rack 16 is completed, the sample rack 16 is transferred from the rack conveying mechanism 15 to the rack conveying mechanism 13, and is returned to the sample loading and unloading section 11 by the rack conveying mechanism 13, and then recovered by the operator. The buffer section 14 is used to temporarily retreat the sample rack 16 when the number of sample racks 16 loaded into the sample loading and unloading section 11 is too large to catch up with the analysis and processing of the mass spectrometer 1, so that the sample rack 16 will not be stranded on the rack conveying mechanism 12. In addition, Figure 1 In the example, a belt conveyor type conveying mechanism is illustrated as the rack conveying mechanism, but the present invention is not limited to this method.

[0011] The pretreatment unit 20 is a unit that performs pretreatment for mass analysis. The content of the pretreatment is not limited. For example, the pretreatment unit 20 performs a process to amplify the target analysis component in the sample. The pretreatment unit 20 includes a reagent cold storage 21 that stores the reagents required for the pretreatment, an incubator 23 that maintains the mixed solution of the reagent and sample at a certain temperature and promotes the reaction, a reaction container supply mechanism 24 that stores the reaction container for mixing the reagent and sample and supplies the reaction container to the incubator 23, a reagent dispensing mechanism 25 that dispenses the reagent from the reagent container stored in the reagent cold storage 21 to the reaction container on the incubator 23, a sample dispensing mechanism 26 that dispenses the sample from the sample container on the sample rack 16 to the reaction container on the incubator 23, and a sample extraction unit 27 that removes components unnecessary for subsequent analysis from the reaction solution of the reagent and sample after the reaction in the incubator 23 is completed.

[0012] The separation unit 30 is a unit that separates the sample pre-processed by the pre-processing unit 20 into multiple components, and the mass spectrometer 40 is a unit (mass spectrometer) that performs mass analysis on the multiple components separated by the separation unit 30. An analysis method using 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).

[0013] Thus, in the mass spectrometer 1, the sample input unit 10, pre-processing unit 20, separation unit 30, and mass spectrometer 40 are modularized, and the device is constructed by combining the modules. Therefore, the overall structure of the device is compact, and by adding modules, the processing capacity of the device can be customized according to the method of use of the device. For example, in Figure 1 In the example of , the modules are combined one by one to form the device, but by combining the separation unit 30 and the mass spectrometer 40 into a set to form the device, the LC-MS analysis capability can be enhanced.

[0014] Figure 2 : shows an example of the arrangement of the units constituting the mass analysis unit 40. The mass analysis unit 40 is composed of a plurality of units, and the main units are shown here. Figure 2 In the illustrated configuration, the mass spectrometer 40 is comprised of an upper housing 206 and a lower housing 208. The upper housing 206 and the lower housing 208 each have metal frames 207 and 209, respectively, which support the units disposed therein. Panels (not shown) are attached to the frames 207 and 209 to protect the interior of the housings. This upper and lower housing structure reduces the front surface area of the mass spectrometer 40, thereby enabling a more compact mass spectrometer 1.

[0015] An ionization unit 201, a mass spectrometer 202, a mass detection unit 203, and an RF output unit 205 are arranged in the upper housing 206. The ionization unit 201 is a unit that ionizes the sample to be analyzed. In the LC-MS method, the sample separated by a liquid chromatograph is used as the sample to be analyzed. The ions generated in the ionization unit 201 are introduced into the mass spectrometer 202. The mass spectrometer 202 allows ions of a specified mass-to-charge ratio (m / z) among the introduced ions to pass through and introduce them into the mass detection unit 203, where the introduced ions are detected and counted. In this embodiment, a quadrupole mass filter is assumed as an example of the mass spectrometer 202.

[0016] use Figure 3A 、 Figure 3B Describe the structure of a quadrupole mass filter. Figure 3B yes Figure 3AThe quadrupole mass filter shown is a cross-sectional view of a surface perpendicular to the central axis. The four cylindrical electrodes 51 to 54 constituting the quadrupole mass filter 41 are arranged parallel to each other in the longitudinal direction at positions equidistant from the central axis (ion light axis). Here, an example is shown in which the first electrode 51 and the third electrode 53 are an electrode pair facing each other in the y-axis direction, and the second electrode 52 and the fourth electrode 54 are an electrode pair facing each other in the x-axis direction. In the quadrupole mass filter 41, a DC voltage U and a high-frequency voltage (hereinafter referred to as RF voltage) Vcosωt (ω: frequency, t: time) are applied in a superimposed manner. In addition, a DC voltage of the same polarity (first polarity) is applied to electrodes facing each other, and a DC voltage of opposite polarity (second polarity) is applied to adjacent electrodes.

[0017] By applying this voltage to the quadrupole mass filter 41, an electric field is generated within it, causing ions introduced from the ionization unit 201 to vibrate in the x-axis or y-axis direction. Ions with a mass-to-charge ratio within a specific range, determined by the applied voltage (U, V, ω), enter a stable vibration state and pass through the quadrupole mass filter 41 to reach the mass detection unit 203. On the other hand, ions with other mass-to-charge ratios undergo unstable vibrations and, due to collisions with electrodes or flight out of the system, do not reach the mass detection unit 203.

[0018] exist Figure 4 Figure 2 shows an example of the configuration of a power supply circuit that applies a superimposed DC voltage U and RF voltage Vcosωt (ω: frequency, t: time) to a quadrupole mass filter 41. The power supply circuit includes a DC control circuit 55, DC amplifiers 56 and 57, an RF control circuit 101, an RF amplifier 107, and a resonant circuit 108. Resonant circuit 108 includes a transformer, and RF amplifier 107 applies RF voltage Vcosωt to the primary coil of the transformer. Furthermore, the transformer includes two secondary coils, one end of which is connected to the y-axis electrode pair 51 and 53 and the x-axis electrode pair 52 and 54, respectively. The other end of one secondary coil is connected to the DC amplifier 56, to which a DC voltage -U is applied. The other end of the other secondary coil is connected to the DC amplifier 57, to which a DC voltage +U is applied. The DC control circuit 55 controls the magnitude of the applied DC voltage, and the RF control circuit 101 controls the amplitude and frequency of the applied RF voltage.

[0019] Back again Figure 2 The following describes the configuration of the units constituting the mass spectrometer 40. Since the ionization unit 201 is assumed to be regularly maintained by an operator, it is configured in a location that is easily accessible to the operator (see Figure 1 ), the front surface of the upper housing 206, so that the operator can easily perform operations. As a result, the mass spectrometer unit 202 and the mass detection unit 203 are necessarily arranged behind the ionization unit 201 in the upper housing 206.

[0020] On the other hand, the control unit that controls the mass spectrometer 40 is arranged in the lower housing 208. The control unit is installed as a plurality of circuit substrates. The plurality of circuit substrates are mounted in a substrate storage unit 204 arranged on the front surface of the lower housing 208. The plurality of circuit substrates include, in addition to the control substrate, an RF substrate carrying the above-mentioned RF amplifier 107, a DC substrate carrying DC amplifiers 56 and 57, and a communication substrate for communicating with external devices. To facilitate maintenance such as substrate replacement, these circuit substrates are preferably arranged on the front surface that is easily accessible to the operator. Therefore, the substrate storage unit 204 is arranged on the front surface of the lower housing 208.

[0021] Here, the RF voltage control of the quadrupole mass filter 41 of the mass spectrometer unit 202 will be described. Figure 5 , a control circuit for the RF voltage (Vcosωt) applied to the quadrupole mass filter 41 is shown. As described above, the ions passing through the mass analysis unit 202 are determined by the voltage (U, V, ω) applied to the quadrupole mass filter 41. Therefore, the RF voltage applied to the quadrupole mass filter 41 is feedback-controlled to apply the desired RF voltage. The RF control circuit 101 includes an RF generator 103 that generates an RF signal, a command voltage generator 104 that generates a command voltage corresponding to the amplitude of the RF signal, an analog multiplier 105, and a multiplier 106. The analog multiplier 105 generates a control signal based on, for example, PI control based on the command voltage output from the command voltage generator 104 and a feedback signal, and transmits it to the multiplier 106. The multiplier 106 multiplies the control signal from the analog multiplier 105 by the RF signal from the RF generator 103. The RF amplifier 107 amplifies the RF signal output from the multiplier 106 and supplies the amplified RF voltage to the resonance circuit 108. The DC voltage from the DC amplifiers 56 and 57 is also input to the resonance circuit 108 (see Figure 4 ), a DC voltage and an RF voltage are superimposed and applied to the quadrupole mass filter 41. The RF voltage output by the resonant circuit 108 is divided by the voltage divider circuit 109, and the amplitude of the RF signal obtained by the voltage division is detected as a DC voltage by the detector circuit 110. The DC voltage detected by the detector circuit 110 is input as a feedback signal to the analog multiplier 105.

[0022] When this RF voltage control circuit is installed in the mass spectrometer unit 40 (module), the RF control circuit 101 and RF amplifier 107 are each mounted on a circuit board and mounted in the substrate storage unit 204. In contrast, to reduce loss and characteristic fluctuations in the resonant circuit 108, the resonant circuit 108 must be located close to the mass spectrometer unit 202. Therefore, the resonant circuit 108 is located in the upper housing 206 as the RF output unit 205. The RF output unit 205 also includes a voltage divider circuit 109 and a detection circuit 110 for generating a feedback signal. As a result, the signal line 102 transmitting the feedback signal becomes a long signal line connecting the RF output unit 205, which is located in the upper housing 206, and the RF control substrate mounted in the substrate storage unit 204, which is located in the lower housing 208.

[0023] When the feedback signal is transmitted over such a long signal line, the accuracy of feedback control may be reduced due to a potential difference (referred to as a GND potential difference) between the reference potential of the detection circuit 110's GND and the reference potential of the RF control circuit 101's GND, or because the long signal line acts as an antenna, easily generating noise. This reduced accuracy of feedback control leads to a decrease in the analytical sensitivity of the mass spectrometer 40.

[0024] Therefore, the signal line 102 of this embodiment is configured to temporarily convert the feedback signal from the detection circuit 110 into a signal with high noise immunity (hereinafter referred to as a noise-resistant signal), transmit the noise-resistant signal over a long distance, and then convert it into a voltage signal. Example 1

[0025] Figure 6 The first feedback control method (Example 1) is shown. In Example 1, the feedback signal from the detection circuit 110 is converted into a signal having a voltage higher than the power supply voltage used in the RF control circuit 101 as a noise-resistant signal. Therefore, an amplifier circuit 111 is provided after the detection circuit 110 in the RF output unit 205, and an attenuation circuit 112 is provided before the analog multiplier 105 in the RF control circuit 101. The amplifier circuit 111 and the attenuation circuit 112 are connected via a signal line 102.

[0026] The feedback signal input to analog multiplier 105 is input together with the command voltage generated by command voltage generator 104. Therefore, the maximum voltage of the command voltage must match the maximum voltage of the feedback signal. For example, a 5V DA converter is used as command voltage generator 104. In Example 1, amplifier circuit 111 amplifies the DC voltage detected by detector circuit 110 to, for example, a maximum of 15V, transmits it over signal line 102, and then converts it into a 5V feedback signal by attenuation circuit 112. By transmitting over signal line 102 at a voltage higher than the power supply voltage used by command voltage generator 104, the effects of ground potential differences and noise generated during transmission can be reduced.

[0027] In Example 1, the feedback signal is amplified and transmitted through the signal line 102 to improve the noise resistance of the feedback signal. This improves the maintainability without reducing the analytical sensitivity of the mass spectrometer 40. Example 2

[0028] Figure 7 The second feedback control method (Example 2) is shown. In Example 2, the feedback signal from the detection circuit 110 is converted into a digital signal as a noise-resistant signal. Therefore, an analog-to-digital converter (ADC) 113 is provided after the detection circuit 110 in the RF output unit 205, and a digital-to-analog converter (DAC) 114 is provided before the analog multiplier 105 in the RF control circuit 101. The ADC 113 and DAC 114 are connected via a signal line 102.

[0029] In Example 2, the feedback signal is transmitted as a digital signal on the signal line 102 , thereby improving the noise resistance of the feedback signal. This improves maintainability without reducing the analytical sensitivity of the mass spectrometer 40 . Example 3

[0030] Figure 8 The third feedback control method (Example 3) is shown. In Example 3, the feedback signal is transmitted (isolated transmission) with electrical insulation between the two ends of signal line 102. For example, the feedback signal from detection circuit 110 is converted into an optical signal as a noise-resistant signal. Therefore, an isolated signal transmitter 115 is provided after detection circuit 110 in RF output unit 205, and an isolated signal receiver 116 is provided before analog multiplier 105 in RF control circuit 101. Isolated signal transmitter 115 and isolated signal receiver 116 are connected via signal line 102. When transmitting as an optical signal, for example, an electro-optical conversion element can be used for isolated signal transmitter 115, a photoelectric conversion element can be used for isolated signal receiver 116, and an optical fiber can be used for signal line 102.

[0031] In Example 3, the feedback signal is transmitted with insulation, thereby improving the noise resistance of the feedback signal. This improves maintainability without reducing the analytical sensitivity of the mass spectrometer 40.

[0032] The present invention is not limited to the above-described embodiments, but also includes various modifications. For example, the above-described embodiments are described in detail to facilitate understanding of the present invention, and are not limited to having all the structures described. In addition, with respect to a portion of the structure of the embodiment, other structures may be added, deleted, or replaced. Label Description

[0033] 1. Mass analysis device 10 Sample input section 11 Sample loading and unloading department 12, 13, 15 bracket transmission mechanism 14 Buffer 20 Pretreatment Department 21 Reagent cold storage 23 incubator 24 Reaction container supply mechanism 25 Reagent dispensing mechanism 26 Sample dispensing mechanism 27 Sample Extraction Department 30 Separation 40 Quality Analysis Department 41 Quadrupole Mass Filter 51 first electrode 52 second electrode 53 third electrode 54 fourth electrode 55 DC control circuit 56, 57DC amplifier 101 RF Control Circuit 102 signal lines 103 RF Generator 104 Command voltage generator 105 Analog Multiplier 106 multipliers 107 RF Amplifier 108 Resonant Circuit 109 Voltage Divider Circuit 110 Detection Circuit 111 amplifier circuit 112 Attenuation Circuit 113 Analog-to-digital converter 114 Digital-to-Analog Converter 115 Insulation signal transmitter 116 Insulation Signal Receiver 201 Ionization Unit 202 Quality Analysis Unit 203 Quality Inspection Unit 204 substrate storage unit 205 RF output unit 206 upper frame 207, 209 framework 208 lower frame.

Claims

1. A mass spectrometer comprising a mass spectrometer unit, characterized in that: The mass spectrometer includes a first frame and a second frame disposed below the first frame. The first housing includes an ionization unit for ionizing an analysis target sample, a mass spectrometry unit having a quadrupole mass filter for introducing ions from the ionization unit and allowing ions of a predetermined mass-to-charge ratio (m / z) to pass therethrough, a mass detection unit for detecting ions that have passed through the mass spectrometry unit, and an RF output unit having a resonant circuit for applying a DC voltage and a high-frequency voltage to the quadrupole mass filter in a superimposed manner. The second housing includes a substrate storage unit that stores at least a control circuit substrate including an RF control circuit for generating a high-frequency signal and an RF substrate including an RF amplifier for amplifying the high-frequency signal and supplying it to the resonant circuit. In the first housing, the ionization unit, the mass analysis unit, and the mass detection unit are arranged from the front surface toward the rear surface, and in the second housing, the substrate storage unit is arranged on the front surface.

2. The mass spectrometer according to claim 1, wherein The mass analysis unit includes a signal line connecting the detection circuit provided in the RF output unit and the RF control circuit. The detection circuit generates a feedback signal indicating the amplitude of the high frequency voltage applied to the quadrupole mass filter. The RF control circuit controls the amplitude of the high-frequency signal according to the feedback signal transmitted through the signal line.

3. The mass spectrometer according to claim 2, wherein The feedback signal is converted into a noise-resistant signal in the RF output unit and transmitted on the signal line, and is further converted into a voltage signal in the RF control circuit.

4. The mass spectrometer according to claim 2, wherein The RF output unit includes an amplifier circuit for amplifying the feedback signal. The RF control circuit includes an attenuation circuit that attenuates the feedback signal transmitted by the signal line.

5. The mass spectrometer according to claim 2, wherein The RF output unit includes an analog-to-digital converter that converts the feedback signal into a digital signal. The RF control circuit includes a digital-to-analog converter that converts the feedback signal transmitted through the signal line into an analog signal.

6. The mass spectrometer according to claim 2, wherein The signal line transmits the feedback signal insulatedly, The RF output unit includes an isolation signal transmitter, and the RF control circuit includes an isolation signal receiver.

7. The mass spectrometer according to any one of claims 1 to 6, wherein have: a pre-processing unit, which pre-processes the sample; and a separation unit that separates the sample pre-processed by the pre-processing unit into a plurality of components, The components of the sample separated by the separation part are used as the analysis target sample, The pre-processing section, the separation section, and the mass analysis section are arranged in this order in a left-right direction perpendicular to the front-rear direction of the mass analysis section.

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