Time-of-flight mass analysis device

Abstract

This aims to avoid wasted time and improve the efficiency of analysis work when the flight tube cannot be properly temperature-controlled due to room temperature being too low or too high. [Solution] One aspect of the present invention is a TOFMS comprising an ion ejection unit (142), a flight tube (144) that forms a space for ejected ions to fly, a vacuum chamber (1) that encloses the flight tube, a temperature control unit (152) that controls the temperature of the flight tube, and a temperature control unit (22) that controls the temperature control operation by the temperature control unit based on the temperature of the flight tube and a target temperature, which are measured indirectly or directly, the TOFMS further comprising a temperature sensor (153) that measures the ambient temperature, which is the temperature outside the vacuum chamber, a prediction unit (23) that predicts the possibility that the temperature of the flight tube will not reach the target temperature or will not fall within a predetermined allowable temperature range including the target temperature, even with temperature control using the temperature control unit, based on the ambient temperature and the target temperature, and a notification unit (24, 4) that notifies the user according to the prediction result.

Description

Technical Field

[0001] The present invention relates to a time-of-flight mass spectrometer (TOFMS).

Background Art

[0002] In a TOFMS, generally, ions to be analyzed are given a certain kinetic energy in an ion injection section, introduced into a flight space formed in a flight tube, and made to fly in the flight space. Then, the time required for the ions to fly a certain distance is measured, and the mass-to-charge ratio (m / z) of the ions is calculated based on the flight time. Therefore, in order to achieve high mass accuracy in a TOFMS, it is important to keep the flight distance constant.

[0003] When the flight tube expands or contracts due to temperature changes, the flight distance changes, resulting in a decrease in mass accuracy. Therefore, in the TOFMS described in Patent Documents 1 and 2, a temperature control section including a heater is provided outside a vacuum chamber in which the flight tube is enclosed, and the flight tube is indirectly heated using the temperature control section so that the detected flight tube temperature directly or indirectly becomes a target temperature (45°C in the example described in Patent Document 2).

[0004] However, since the heating capacity of the heater is limited, if the room temperature is too low, the flight tube may not reach the target temperature. Conversely, if the room temperature is too high, the flight tube temperature may exceed the target temperature. Therefore, in a conventional TOFMS, it is detected whether the flight tube temperature is within a predetermined allowable temperature range including the target temperature, and when the flight tube temperature does not fall within the allowable temperature range even after a predetermined time has elapsed, a temperature control error (timeout error) is displayed to alert the user.

Prior Art Documents

Patent Documents

[0005] [Patent Document 1] International Publication No. 2019 / 224948 [Patent Document 2] International Publication No. 2019 / 220497 [Overview of the project] [Problems that the invention aims to solve]

[0006] Typically, vacuum chambers and flight tubes have very large heat capacities and high thermal time constants. Therefore, it takes a considerable amount of time (e.g., tens of hours) for the flight tube temperature to stabilize near the target temperature after temperature control is initiated. Consequently, as mentioned above, the predetermined time for determining a timeout error is set to be quite long, and it may take tens of hours after the device is started before the timeout error is displayed, revealing that the ambient temperature is too low or too high. In such cases, the user has to wait an unnecessarily long time, reducing the efficiency of the analysis.

[0007] This invention was made to solve these problems, and its main objective is to provide a TOFMS that can appropriately temperature control the flight tube to ensure high mass accuracy, while reducing wasted work time related to temperature control and thereby improving the efficiency of analytical work. [Means for solving the problem]

[0008] One aspect of the present invention is a TOFMS comprising: an ion ejection unit; a flight tube forming a space through which ions ejected from the ion ejection unit fly; a vacuum chamber enclosing the flight tube; a temperature control unit for temperature-controlling the flight tube; and a temperature control unit for controlling the temperature-controlling operation of the temperature control unit based on the temperature of the flight tube and a target temperature, which are measured indirectly or directly. A temperature sensor for measuring the ambient temperature, which is the temperature outside the vacuum chamber, A prediction unit that predicts, based on the ambient temperature and the target temperature, the possibility that the temperature of the flight tube will not reach the target temperature or will not fall within a predetermined allowable temperature range including the target temperature, even with temperature control using the temperature control unit. A notification unit that notifies the user according to the prediction results from the prediction unit, It is equipped with. [Effects of the Invention]

[0009] In the TOFMS according to the above embodiment of the present invention, if it is predicted that the temperature of the flight tube will not fall within (reach) the allowable temperature range even with temperature control using the temperature control unit, for example, in the initial stages of analysis preparation work such as before the start of temperature control of the flight tube, the notification unit can notify the user of a warning. Thus, according to the present invention, the user can grasp the possibility that the temperature control of the flight tube may not be properly performed in the initial stages of analysis preparation work without having to wait a long time until the actual temperature change of the flight tube is determined. If this possibility exists, the user can then quickly take appropriate measures, such as adjusting the room temperature or changing the target temperature of the temperature control itself. This makes it possible to avoid wasted time in analysis, shorten the time required for analysis work, and improve the efficiency of analysis work, even in situations where the room temperature is too low or too high. [Brief explanation of the drawing]

[0010] [Figure 1] A diagram showing the main components of Q-TOFMS, one embodiment of the present invention. [Figure 2] This figure shows an example of a control flowchart for the temperature control startup of the flight tube in the Q-TOFMS of this embodiment. [Figure 3] A schematic diagram showing the relationship between room temperature and the duty cycle for heater control, where Ta is the target temperature for temperature control of the flight tube. [Figure 4] A diagram illustrating the configuration of the part related to the temperature control operation of the flight tube in a modified Q-TOFMS. [Figure 5]This figure shows an example of a control flowchart during temperature control of the flight tube in the Q-TOFMS of the above modified example. [Modes for carrying out the invention]

[0011] A quadrupole time-of-flight mass spectrometer (Q-TOFMS), which is one embodiment of the TOSMS according to the present invention, will be described with reference to the attached drawings. In this embodiment, the TOFMS is a reflectron-type TOFMS with orthogonal acceleration, but this is merely one example, and as will be described later, the present invention is not limited to orthogonal acceleration, nor is it limited to a reflectron-type TOFMS.

[0012] [Q-TOFMS Configuration and Overview of Operation] Figure 1 is an overall diagram of the Q-TOFMS of this embodiment. The configuration and operation of this Q-TOFMS are outlined below.

[0013] In this Q-TOFMS, an ionization chamber 10 is connected to the front of the vacuum chamber 1. The inside of the vacuum chamber 1 is roughly divided into four chambers: a first intermediate vacuum chamber 11, a second intermediate vacuum chamber 12, a first analysis chamber 13, and a second analysis chamber 14. The ionization chamber 10 is at approximately atmospheric pressure, while each chamber within the vacuum chamber 1 is evacuated by an appropriate vacuum pump (not shown). As a result, this Q-TOFMS has a multi-stage differential pumping system in which the vacuum level increases in stages from the ionization chamber 10 to the first intermediate vacuum chamber 11, the second intermediate vacuum chamber 12, the first analysis chamber 13, and the second analysis chamber 14.

[0014] An electrospray ion (ESI) source 101 is located in the ionization chamber 10. The ESI source 101 sprays the liquid sample, supplied from a liquid chromatograph (not shown), into the ionization chamber 10 while imparting an electric charge to the sample. This ionizes the compounds in the liquid sample. However, the ionization method is not limited to this, and other ionization sources such as atmospheric pressure chemical ion sources, atmospheric pressure photoion sources, and probe electrospray ion sources may also be used.

[0015] The ionization chamber 10 and the first intermediate vacuum chamber 11 communicate with each other through a narrow-diameter desolvation tube 102. As described above, the ions and fine charged droplets derived from the sample components generated in the ionization chamber 10 are drawn into the desolvation tube 102 and sent to the first intermediate vacuum chamber 11 due to the pressure difference between the ionization chamber 10 and the first intermediate vacuum chamber 11. The desolvation tube 102 is heated to an appropriate temperature. When the charged droplets pass through the inside of the desolvation tube 102, the vaporization of the solvent in the droplets is promoted, and the generation of ions is promoted.

[0016] A multipole-type ion guide 111 is arranged in the first intermediate vacuum chamber 11. By this ion guide 111, the ions are converged near the ion optical axis C1 and enter the second intermediate vacuum chamber 12 through the opening at the top of the skimmer 112. A multipole-type ion guide 121 is also arranged in the second intermediate vacuum chamber 12. By this ion guide 121, the ions are sent from the second intermediate vacuum chamber 12 to the first analysis chamber 13.

[0017] In the first analysis chamber 13, a quadrupole mass filter 131 for separating ions according to m / z, a collision cell 132 provided with an ion guide 133 inside, and a front-stage transfer electrode 134 for transporting the ions emitted from the collision cell 132 are arranged. The ions incident on the first analysis chamber 13 are introduced into the quadrupole mass filter 131, and only the ions having a specific m / z corresponding to the voltage applied to the quadrupole mass filter 131 pass through the quadrupole mass filter 131. A collision gas such as argon is continuously or intermittently supplied into the collision cell 132. The ions incident on the collision cell 132 with a predetermined energy collide with the collision gas and are dissociated by collision-induced dissociation, generating various product ions.

[0018] The various product ions emitted from the collision cell 132 are converged by the front-stage transfer electrode 134 and sent to the second analysis chamber 14. In the second analysis chamber 14, a rear-stage transfer electrode 141, an orthogonal acceleration section 142, a second acceleration electrode section 143, a flight tube 144, a reflectron 145, a detector 148, etc. are arranged. The ions formed into a thin beam by the rear-stage transfer electrode 141 are emitted in a direction substantially orthogonal to the incident direction of the beam (downward in FIG. 1) in the orthogonal acceleration section 142. The emitted ions are introduced into the flight space 147 in the flight tube 144 through the second acceleration electrode section 143. By the flight tube 144 and the reflectron 145, an electric field for causing the ions to fly back along a path shown as C2 in FIG. 1 is formed in the flight space 147. As a result, the ions fly again after being turned back and reach the detector 148.

[0019] The ions emitted from the orthogonal acceleration section 142 as an ion emission section fly at a speed corresponding to the m / z of the ions. Therefore, the various ions accelerated simultaneously are separated according to m / z during flight and reach the detector 148 with a time difference. The detector 148 generates a detection signal in real time according to the amount of the ions that have arrived. A data processing section (not shown) that has received the detection signal calculates the flight time from the detection signal and creates a mass spectrum obtained by converting the flight time into m / z. Thereby, a mass spectrum of product ions reflecting the structure of a specific compound in the liquid sample is obtained. Further, in this Q-TOFMS, by allowing the ions to pass through the quadrupole mass filter 131 without dissociating the ions in the collision cell 132, a mass spectrum corresponding to the compound contained in the liquid sample can be obtained.

[0020] [Configuration related to temperature control of the flight tube] The flight tube 144 is located in a second analysis chamber 14 formed within the vacuum chamber 1. Specifically, the flight tube 144, which is made of a metal such as stainless steel and is roughly rectangular in shape, is attached to the inner wall surface of the vacuum chamber 1 via a plurality of support members 146. A temperature control unit 151, including a heater (not shown), is attached to the outer wall surface of the vacuum chamber 1 for indirectly controlling the temperature of the flight tube 144. The temperature control unit 151 may be capable of cooling the flight tube 144, or it may be capable of both heating and cooling. Furthermore, the temperature control unit 151 may be configured to directly control the temperature of the flight tube 144, rather than indirectly. In this embodiment, there is only one temperature control unit 151, but multiple temperature control units 151 may be provided, as in the apparatus described in Patent Document 1.

[0021] A device temperature sensor 152 is mounted on the outer wall surface of the vacuum chamber 1, specifically at the location where one of the support members 146 is attached. This device temperature sensor 152 indirectly detects the temperature of the flight tube 144, and its detection signal is input to the control unit 2. In addition, an indoor temperature sensor 153 is provided at an appropriate location outside the vacuum chamber 1 to detect the ambient temperature at an appropriate distance from the vacuum chamber 1. The detection signal from this indoor temperature sensor 153 is also input to the control unit 2. Similar to the temperature control unit 151, multiple device temperature sensors 152 can be provided. Furthermore, the device temperature sensor 152 may more directly detect the temperature of the flight tube 144. Multiple indoor temperature sensors 153 can also be provided.

[0022] The control unit 2 typically consists of a computer including a CPU, and includes, as functional blocks, a target temperature setting unit 21, a temperature control unit 22, a temperature fluctuation prediction unit 23 during temperature control startup, and a notification processing unit 24. Each of these functional blocks can be realized by executing software (programs) installed on the computer, but at least a part of them may be configured by hardware circuits such as a digital signal processor. The control unit 2 is also connected to an input unit 3 and a notification unit 4, which are user interfaces. The notification unit 4 may be a display or other indicator for visual notification, or it may be an audible or voice notification such as a buzzer.

[0023] [Flight tube temperature control operation] During analysis, if the flight tube 144 expands or contracts due to heat, the flight distance of ions changes, causing a mass error. To avoid this, in this Q-TOFMS, the temperature control unit 22 included in the control unit 2 controls the temperature control operation of the temperature control unit 151 so that the flight tube temperature is maintained within a predetermined allowable temperature range near the target temperature, based on the target temperature set in the target temperature setting unit 21 and the flight tube temperature estimated based on the detection signal from the device temperature sensor 152. Specifically, the power supplied to the heater included in the temperature control unit 151 is pulse width modulation (PWM) controlled, and the temperature control unit 22 controls the heating power by adjusting the duty cycle of the PWM control.

[0024] The target temperature is set to a temperature that is appropriately higher than the typical room temperature (ambient temperature). In the TOFMS of this embodiment, the standard target temperature is 42°C, and with a tolerance of 0.5°C from that target temperature, the allowable temperature range is 42 ± 0.5°C (41.5 to 42.5°C). However, 42°C is the default target temperature, and the target temperature can be changed within a predetermined temperature range by operation from the input unit 3 by the user. The following explanation will primarily describe the case where the target temperature is 42°C, but it will be clear from the following explanation that the target temperature does not have to be 42°C.

[0025] When the device is stopped or when the temperature control unit 151 is not performing temperature control operations, the temperature of the flight tube 144 is close to room temperature and considerably lower than the target temperature. Therefore, in order to perform analysis, it is necessary to first start the temperature control operation by the temperature control unit 151 and bring the temperature of the flight tube 144 within the allowable temperature range. Figure 2 shows an example of a control flowchart for starting up the temperature control of the flight tube in the Q-TOFMS of this embodiment.

[0026] For example, when the user instructs the input unit 3 to start up the temperature control (step S1), the temperature fluctuation prediction unit 23 reads the detection signal from the room temperature sensor 153 and detects the current room temperature Tr (step S2). Next, the temperature fluctuation prediction unit 23 obtains information on the target temperature Ta from the target temperature setting unit 21 and calculates the temperature difference ΔT (= Ta - Tr) between the room temperature Tr and the target temperature Ta (step S3). For example, if the target temperature Ta is 42℃ and the current room temperature Tr is 25℃, the temperature difference ΔT = 17.

[0027] The larger the temperature difference ΔT, the more the temperature control unit 22 needs to supply greater heating power to the temperature control unit 151 in order to bring the temperature of the flight tube 144 closer to the target temperature Ta. However, since there is a limit to the heating power that can be supplied, if the temperature difference ΔT is too large, even if the maximum heating power is supplied to the temperature control unit 151, the temperature of the flight tube 144 will not reach the allowable temperature range. Conversely, once the device is started up, the temperature of the flight tube 144 rises to a certain extent due to heat from various components even without heating by the temperature control unit 151. Therefore, if the temperature difference ΔT is too small, the temperature of the flight tube 144 may exceed the allowable temperature range even without operating the temperature control unit 151. To this end, the temperature fluctuation prediction unit 23 at the start of temperature control determines whether the temperature difference ΔT is greater than 27°C (step S4), and if it is not greater than 27°C, it then determines whether the temperature difference ΔT is less than 6°C (step S6). Step S4 is a process to determine whether the room temperature is too low relative to the target temperature, and step S6 is a process to determine whether the room temperature is too high relative to the target temperature.

[0028] Here, we will explain how the temperature criteria for "27°C" and "6°C" in steps S4 and S6 are determined. Figure 3 is a schematic diagram experimentally showing the relationship between room temperature and the duty cycle in the heater's PWM control, when the target temperature for temperature control of the flight tube 144 is defined as Ta. When the duty cycle is 100%, the heating power is at full power, and when the duty cycle is 0%, the heating power is zero. As shown in Figure 3, the duty cycle required to heat the flight tube 144 to the target temperature Ta increases linearly as the room temperature decreases. Ts is the lowest room temperature at which the target temperature Ta can be reached when temperature control is performed with a 100% duty cycle, i.e., full power heating. If the room temperature is below this, the temperature of the flight tube 144 cannot reach the target temperature Ta even if temperature control is performed with full power heating.

[0029] However, if the power supply to the heater is controlled with a duty cycle close to 100% or 0%, the control's ability to track temperature fluctuations will decrease, potentially leading to reduced temperature stability in the flight tube 144 and consequently, reduced mass stability in the analysis. Therefore, a 20% margin is considered necessary to ensure temperature stability, and an appropriate duty cycle range of 20-80% is assumed. The room temperature range in which the flight tube 144 can be appropriately temperature-controlled is defined as TL-Th.

[0030] As an example, when the target temperature Ta is 42°C, TL is 15°C and Th is 36°C. Therefore, here, when the target temperature is 42°C, Ta - TL = 27°C is defined as the determination criterion in step S4, and Ta - Th = 6°C is defined as the determination criterion in step S6. Of course, when the target temperature Ta is different, the determination criterion for the temperature difference ΔT can be determined in the same way. However, the margin of the duty ratio of the PWM control is not limited to the above description, and it can be easily conceived that the determination method will be different depending on the heating control method of the temperature control unit 151. That is, the determination process in step S4 may be a process of predicting that the temperature of the flight tube 144 cannot reach the allowable temperature range even with appropriate temperature control, and the determination process in step S6 may be a process of predicting that the temperature of the flight tube 144 will exceed the allowable temperature range even with appropriate temperature control.

[0031] In any case, when it is determined as YES in steps S4 and S6, it indicates that even if the temperature control is performed by the temperature control unit 151, the temperature of the flight tube 144 is highly likely not to converge to the allowable temperature range appropriate for analysis.

[0032] Note that since the determination process in step S4 is a determination based on the inequality "Ta - Tr > 27", it is obvious that it is substantially the same even if this formula is transformed and the determination is made according to the formula "Ta - 27 > Tr". Similarly, the determination process in step S6 is also substantially the same even if the determination is made according to the formula "Ta - 6 < Tr".

[0033] When it is determined as YES in step S4, the notification processing unit 24 outputs a warning notification indicating that the ambient temperature of the device is too low through the notification unit 4 (step S5). Also, when it is determined as YES in step S6, the notification processing unit 24 outputs a warning notification indicating that the ambient temperature of the device is too high through the notification unit 4 (step S7). On the other hand, when it is determined as NO in step S6, since the ambient temperature can be estimated to be appropriate, the process ends without performing the above warning notification at the time of starting temperature control.

[0034] More specifically, the warning in step S5 should include a display or audio message stating, "The ambient temperature around the device is too low, which may cause the flight tube temperature to be unstable. Please raise the room temperature to X°C or higher, or lower the target temperature to Y°C or lower." Similarly, the warning in step S7 should include a display or audio message stating, "The ambient temperature around the device is too high, which may cause the flight tube temperature to be unstable. Please lower the room temperature to X°C or lower, or raise the target temperature to Y°C or higher."

[0035] A user who receives a warning notification as described above can, for example, change the room temperature by adjusting the air conditioning in the room where the Q-TOFMS is located. Conventionally, it was not possible to know at the time of temperature control startup whether the temperature of the flight tube 144 would ultimately fall within the acceptable temperature range, and the user could only find out that the room temperature was not appropriate after several tens of hours had passed since temperature control startup and a timeout error occurred. In contrast, with the Q-TOFMS of this embodiment, it is possible to know immediately after temperature control startup that there is a high probability that the temperature of the flight tube 144 will ultimately not fall within the acceptable temperature range. Therefore, problems caused by the room temperature being too low or too high can be resolved quickly without wasting unnecessary waiting time. Furthermore, analysis can be performed after several tens of hours have passed since temperature control startup, once the temperature of the flight tube 144 has reliably fallen within the acceptable temperature range.

[0036] A user who receives the above-mentioned warning notification may, instead of adjusting the room temperature, adjust the target temperature Ta from the input unit 3 to substantially reduce or increase the temperature difference ΔT. However, changing the target temperature of the temperature control from the default value (42°C in this case) will change the flight distance compared to when the temperature of the flight tube 144 is at the default value. Since a change in flight distance alters the relationship between the ion flight time and the m / z value, it usually becomes necessary to repeat the process of acquiring mass calibration data by performing actual measurements using a standard sample. Although it is possible to perform mass calibration using mass calibration data obtained in advance or provided by the instrument manufacturer without performing such actual measurements, if high-precision analysis is required, it is preferable to acquire mass calibration data by actual measurement as close to the actual measurement of the target sample as possible. Therefore, considering the effort required to acquire such mass calibration data, it is preferable to adjust the room temperature rather than changing the target temperature Ta.

[0037] As described above, when a temperature control startup is instructed, the temperature fluctuation prediction unit 23 performs the processing shown in Figure 2, and in parallel, the temperature control unit 22 starts the temperature control operation by the temperature control unit 151 based on the detection signal from the device temperature sensor 152 and the target temperature Ta. Therefore, within, for example, several tens of hours from the start of temperature control startup, the temperature of the flight tube 144 will reliably converge to the allowable temperature range and become ready for analysis.

[0038] It should be noted that, rather than being a problem with the room temperature or target temperature settings, there may be a malfunction in the temperature control unit 151, for example, which could prevent the temperature of the flight tube 144 from reaching near the target temperature. Therefore, it is preferable that the Q-TOFMS of this embodiment also be equipped with a function, similar to those found in conventional devices, that detects whether the flight tube temperature is within a predetermined allowable temperature range including the target temperature, displays a temperature control error if the flight tube temperature is outside the allowable temperature range for a certain period of time or longer, and displays a message indicating that analysis is possible if the flight tube temperature is converging within the allowable temperature range.

[0039] Furthermore, while the above description only involves issuing a warning notification when the ambient temperature is determined to be too high or too low, prompting the user to resolve the problem, it is also possible to take more proactive actions to resolve the problem. Specifically, if YES is determined in steps S4 and S6 above, the target temperature Ta may be automatically changed according to the room temperature at that time. For example, as described in Patent Document 2, the target temperature Ta may be changed to a temperature calculated by adding a certain value to the detected room temperature (ambient temperature) (or subtracting it if cooling is performed by the temperature control unit 151). However, as mentioned above, it is usually desirable to reacquire mass calibration data when changing the target temperature, so it is preferable to automatically change the target temperature and notify the user of the change.

[0040] [Configuration and operation of a modified QTOFMS] Next, a modified example of the Q-TOFMS of the above embodiment will be described with reference to Figures 4 and 5. Figure 4 is a configuration diagram of the part related to the temperature control operation of the flight tube in this modified Q-TOFMS, and Figure 5 is a diagram showing an example of a control flowchart during temperature control of the flight tube in this modified Q-TOFMS. In Figure 4, all the internal configuration of the vacuum chamber 1 in the Q-TOFMS shown in Figure 1 has been omitted, and the same or equivalent components as those shown in Figure 1 are denoted by the same reference numerals.

[0041] In this modified Q-TOFMS, during temperature control startup, the room temperature is detected, similar to the above embodiment, and immediately after temperature control startup, it is predicted whether the temperature of the flight tube 144 will fall within the allowable temperature range based on the room temperature and the target temperature. In addition, this modified Q-TOFMS continuously predicts the possibility that the temperature of the flight tube 144 may deviate from the allowable temperature range while temperature control is being performed.

[0042] As shown in Figure 4, in this modified Q-TOFMS, the control unit 2 further includes a temperature control model information storage unit 25 and a temperature control fluctuation prediction unit 26 as functional blocks. The temperature control model information storage unit 25 stores a pre-created temperature control model function. The temperature control model function is a model function that predicts the temporal fluctuation of the temperature of the flight tube 144, with room temperature Tr, vacuum chamber 1 temperature Tc, flight tube 144 temperature (current temperature) Tf, and target temperature Ta as variables. Such a model function can be experimentally determined in advance by the equipment manufacturer using a multivariate analysis method. The temperature control fluctuation prediction unit 26 receives the temperature control model function from the temperature control model information storage unit 25, a detection signal from the room temperature sensor 153, a target temperature Ta from the target temperature setting unit 21, and a detection signal from the equipment temperature sensor 152, and its output is input to the notification processing unit 24.

[0043] As described above, under the control of the temperature control unit 22, the temperature of the flight tube 144 is controlled by the temperature control unit 151 so that its temperature falls within an allowable temperature range centered on the target temperature Ta. During this temperature control, the temperature fluctuation prediction unit 26 reads a detection signal from the room temperature sensor 153 corresponding to the current room temperature Tr, and a detection signal from the device temperature sensor 152 corresponding to the outer wall temperature Tc of the vacuum chamber 1 (steps S11, S12). Then, based on the outer wall temperature Tc of the vacuum chamber 1, it estimates the temperature Tf of the flight tube 144 using a calculation formula that has been experimentally obtained in advance (step S13).

[0044] The temperature fluctuation prediction unit 26 further applies the room temperature Tr, the temperature Tc of the vacuum chamber 1, the temperature Tf of the flight tube 144, and the target temperature Ta to the temperature control model function to predict the temporal fluctuation of the temperature of the flight tube 144. Based on the prediction results, it estimates the possibility that the temperature of the flight tube 144 will deviate from the allowable temperature range, and if there is a possibility of deviation, it estimates the time required until the deviation occurs (step S14).

[0045] If it is predicted in step S14 that the temperature of the flight tube 144 may deviate from the allowable temperature range, then in step S15, the result is determined to be YES, and the notification processing unit 24 outputs a warning notification from the notification unit 4 indicating the possibility of this happening, along with the predicted time required until the temperature deviates from the allowable temperature range (step S16). Specifically, a warning such as "The temperature may be outside the temperature control stable range after X hours. Please change the temperature control target temperature or the room temperature" can be displayed. On the other hand, if the result in step S15 is determined to be NO, then there is no problem with the temperature control of the flight tube 144, at least at that point, so the process returns to step S11. By repeatedly performing the processes in steps S11 to S16, it is possible to continuously monitor the possibility of the temperature of the flight tube 144 deviating from the allowable temperature range while temperature control is being performed, i.e., while analysis is being executed.

[0046] Even if the temperature of the flight tube 144 has initially stabilized within the acceptable temperature range, if the room temperature drops or rises drastically during the analysis, for example, due to the air conditioning being shut off, the temperature of the flight tube 144 may fall outside the acceptable temperature range after a certain period of time has elapsed. In conventional equipment, a temperature control error will occur in such cases, but this error will only appear a considerable time after the room temperature has changed. This is because, as already mentioned, the heat capacity of the vacuum chamber 1 and the flight tube 144 is quite large, so even if the room temperature changes significantly, it takes time for the temperature of the vacuum chamber 1 and the flight tube 144 to actually change. Therefore, in conventional equipment, if the analysis is performed at the time the temperature control error occurs, there is a risk that highly accurate data cannot be collected.

[0047] In contrast, in this modified Q-TOFMS, even if the room temperature drops or rises drastically while the flight tube 144 temperature is stable during analysis, and there is a risk that the temperature of the flight tube 144 will fall outside the acceptable temperature range after several hours to tens of hours, the system will notify the user, along with a predicted time, that the temperature of the flight tube 144 may fall outside the acceptable temperature range shortly after the change in room temperature. Therefore, the user can take appropriate measures, such as adjusting the air conditioning to return the changed room temperature to its original state. Alternatively, the user can postpone adjusting the room temperature if the analysis can be completed with ample margin within the predicted time, or, if analyzing multiple samples consecutively, adjust the number of samples so that the analysis can be completed within the predicted time, thereby enabling planned and efficient analysis.

[0048] [Other variations] In the Q-TOFMS according to the above embodiment and its modifications, the device temperature sensor 152 was attached to the outer wall surface of the vacuum chamber 1 and indirectly detected the temperature of the flight tube 144. However, the temperature of the flight tube 144 may be detected more directly inside the vacuum chamber 1. Similarly, the temperature control unit 151 may control the temperature of the flight tube 144 more directly, rather than controlling the temperature of the flight tube 144 via the vacuum chamber 1.

[0049] Furthermore, either or both of the device temperature sensor 152 and the temperature control unit 151 may be provided in multiples, not just one. When multiple device temperature sensors 152 and temperature control units 151 are provided, as described in Patent Document 1, the device temperature sensor 152 and temperature control unit 151 can be provided at different positions on the outer wall surface of the vacuum chamber 1 along the axial direction (vertical direction in Figure 1) of the flight tube 144, and / or at different positions on the outer wall surface of the vacuum chamber 1 in a plane perpendicular to the axis of the flight tube 144. Of course, multiple indoor temperature sensors 153 may be provided, and the average value of the temperatures detected by these multiple indoor temperature sensors 153 or other calculated values ​​may be used as the room temperature Tr.

[0050] Furthermore, the TOFMS can be configured not only as the orthogonal acceleration method shown in Figure 1, but also, for example, as an ion trap or a matrix-assisted laser desorption ion source. Moreover, the TOFMS is not limited to the reflectron type; the present invention can be applied to any TOFMS in which a flight space is formed inside the flight tube and the flight distance changes depending on the temperature of the flight tube.

[0051] Furthermore, the above embodiments and modifications are merely examples of the present invention, and it is clear that any modifications, changes, or additions made within the scope of the present invention will still be included in the claims of this patent application.

[0052] [Various embodiments and their functions and effects] Those skilled in the art will understand that the exemplary embodiments described above are specific examples of the following embodiments.

[0053] (Section 1) One embodiment of the TOFMS according to the present invention is a TOFMS comprising: an ion ejection unit; a flight tube forming a space through which ions ejected from the ion ejection unit fly; a vacuum chamber enclosing the flight tube; a temperature control unit for temperature-controlling the flight tube; and a temperature control unit that controls the temperature-controlling operation by the temperature control unit based on the temperature of the flight tube and a target temperature, which are measured indirectly or directly. A temperature sensor for measuring the ambient temperature, which is the temperature outside the vacuum chamber, A prediction unit that predicts, based on the ambient temperature and the target temperature, the possibility that the temperature of the flight tube will not reach the target temperature or will not fall within a predetermined allowable temperature range including the target temperature, even with temperature control using the temperature control unit. A notification unit that notifies the user according to the prediction results from the prediction unit, It is equipped with.

[0054] In the TOFMS described in paragraph 1, for example, in the initial stages of analysis preparation work, such as before the start of temperature control of the flight tube, the prediction unit predicts the possibility that the temperature of the flight tube may not fall within a predetermined allowable temperature range, based on the actual ambient temperature measured by the temperature sensor and the target temperature, even if temperature control is performed using the temperature control unit. This occurs, for example, when the ambient temperature is extremely low or high compared to the target temperature. If it is predicted that there is a high possibility that the temperature of the flight tube will not fall within the predetermined allowable temperature range, the notification unit issues a warning notification to the user.

[0055] Thus, with the TOFMS described in paragraph 1, users can identify the possibility that the temperature of the flight tube may not be properly controlled in the early stages of the analysis preparation work, without having to wait a long time until the actual temperature changes of the flight tube are known. If this is the case, they can quickly take appropriate measures depending on the situation, such as adjusting the room temperature or changing the target temperature itself. This makes it possible to avoid wasted time in the analysis, shorten the time required for the analysis work, and improve the efficiency of the analysis work, even in situations where the room temperature is initially too low or too high.

[0056] (Paragraph 2) The TOFMS described in Paragraph 1 may further include a target temperature setting unit that changes the target temperature according to the prediction result from the prediction unit.

[0057] In the TOFMS described in paragraph 2, the target temperature setting unit lowers the target temperature when the ambient temperature is too low, and raises the target temperature when the ambient temperature is too high. This allows the temperature of the flight tube to reach the target temperature or stay within the allowable temperature range by temperature control using the temperature control unit, without adjusting the room temperature. Therefore, even when performing analysis in a location that does not have a function to adjust the room temperature, analysis can be performed with high mass accuracy.

[0058] (3) In the TOFMS described in paragraph 1 or 2, the prediction unit may predict the possibility that the temperature of the flight tube will not reach the target temperature or fall within the predetermined allowable temperature range before or immediately after the temperature control unit starts temperature control.

[0059] According to the TOFMS described in Section 3, a warning is issued immediately after the device's temperature control is started if the room temperature is too low or too high. Therefore, the user can recognize that the room temperature is too low or too high with virtually no waiting time and take appropriate action, such as adjusting the room temperature. Consequently, analysis can proceed efficiently without causing unnecessary waiting time.

[0060] (Article 4) In the TOFMS described in any one of paragraphs 1 to 3, the prediction unit may predict the possibility that the temperature of the flight tube will not reach the target temperature or fall within the predetermined allowable temperature range by comparing the difference between the ambient temperature and the target temperature with a predetermined judgment criterion value.

[0061] The TOFMS described in Section 4 can predict with high accuracy whether the flight tube temperature will not reach the target temperature or fall outside the acceptable temperature range through simple calculations. Therefore, the program (computer software) required to implement this function can be simple, and the computer load will be small.

[0062] (Clause 5) In the TOFMS described in any one of paragraphs 1 to 4, the prediction unit may predict the possibility that the temperature of the flight tube will not reach the target temperature or fall within the predetermined allowable temperature range, assuming that the temperature control unit operates within a range between a capacity that is a predetermined margin lower than the maximum capacity and a capacity that is a predetermined margin higher than the minimum capacity.

[0063] When a temperature control unit is driven by PWM control, its capacity generally depends on the duty cycle of the PWM control. Therefore, the range of the temperature control unit's capacity can be rephrased as the range of the PWM duty cycle. Typically, the maximum capacity is at a 100% duty cycle, and the minimum capacity is at a 0% duty cycle. When a temperature control unit is operated at or very close to its maximum capacity, it has little capacity margin, making it difficult to respond to changes in ambient temperature and reducing temperature stability. This leads to a decrease in mass stability.

[0064] In contrast, in the TOFMS described in Section 5, the temperature control unit does not operate when the duty cycle of the PWM control is near 100% or 0%, resulting in high temperature stability, which in turn ensures mass stability during analysis.

[0065] (Clause 6) The TOFMS described in any one of paragraphs 1 to 5 further comprises a temperature control prediction unit that predicts the possibility of the temperature of the flight tube falling outside the target temperature or the allowable temperature range based on the ambient temperature, the target temperature, and the temperature of the flight tube, during temperature control by the temperature control unit after the temperature of the flight tube has reached the target temperature or fallen within the predetermined allowable temperature range, and the notification unit may provide notification to the user according to the prediction result by the temperature control prediction unit.

[0066] Even if the temperature of the flight tube stabilizes due to temperature control and analysis begins, if the room temperature fluctuates significantly during the analysis, the temperature of the flight tube may deviate from the acceptable temperature range after a considerable amount of time has passed since that point.

[0067] In contrast, according to the TOFMS described in Section 6, even if the flight tube temperature has temporarily fallen within the acceptable temperature range, a warning notification is promptly issued if there is a possibility that the room temperature will fluctuate significantly and cause the flight tube temperature to deviate from the acceptable temperature range. This allows the user to quickly take appropriate action, such as checking the room temperature. Furthermore, it is possible to avoid situations where analysis is performed when the flight tube temperature is outside the acceptable temperature range, thereby preventing the execution of inaccurate and wasteful analyses.

[0068] (Clause 7) In the TOFMS described in paragraph 6, the temperature control prediction unit may predict the time required until the temperature of the flight tube falls outside the target temperature or the allowable temperature range, and the notification unit may notify the user of the predicted time required.

[0069] In the TOFMS described in Section 7, if the room temperature fluctuates significantly during analysis and the temperature of the flight tube may deviate from the acceptable temperature range, the time required until this condition occurs, i.e., the time during which the analysis can be continued appropriately, is notified. This allows for appropriate measures to be taken, such as confirming whether the analysis can be completed within the notified time, or adjusting the number of samples so that the analysis can be completed within that time, even if the room temperature cannot be controlled. As a result, unnecessary analyses can be avoided, and efficient analytical work can be carried out. [Explanation of symbols]

[0070] 1… Vacuum Chamber 10... Ionization Chamber 11…First intermediate vacuum chamber 12…Second intermediate vacuum chamber 13…1st analysis room 14…Second analysis room 101... Electrospray ion (ESI) source 102... Desolvation tube 111, 121, 133… Aeon Guide 112...Skimmer 131... Quadrupole Mass Filter 132...Collision cell 134…Pre-transfer electrode 141...Post-stage transfer electrode 142... Orthogonal acceleration section 143...Second accelerating electrode section 144... Flight Tube 145...Reflectron 146...Support member 147... Flight Space 148… Detector 151…Temperature control section 152... Device temperature sensor 153... Indoor temperature sensor 2…Control Unit 21…Target temperature setting section 22...Temperature control unit 23...Temperature fluctuation prediction unit during temperature control startup 24... Notification Processing Unit 25...Temperature control model information storage unit 26...Temperature fluctuation prediction section in temperature control 3...Input section 4… Hochi Department

Claims

1. A TOFMS comprising: an ion ejection unit; a flight tube forming a space through which ions ejected from the ion ejection unit fly; a vacuum chamber enclosing the flight tube; a temperature control unit for temperature-controlling the flight tube; and a temperature control unit that controls the temperature-controlling operation by the temperature control unit based on the temperature of the flight tube and a target temperature, which are measured indirectly or directly, respectively. A temperature sensor for measuring the ambient temperature, which is the temperature outside the vacuum chamber, A prediction unit that predicts, based on the ambient temperature and the target temperature, the possibility that the temperature of the flight tube will not reach the target temperature or will not fall within a predetermined allowable temperature range including the target temperature, even with temperature control using the temperature control unit. A notification unit that notifies the user according to the prediction results from the prediction unit, A time-of-flight mass spectrometer equipped with the following features.

2. The time-of-flight mass spectrometer according to claim 1, further comprising a target temperature setting unit that changes the target temperature according to the prediction result from the prediction unit.

3. The time-of-flight mass spectrometer according to claim 1, wherein the prediction unit predicts the possibility that the temperature of the flight tube will not reach the target temperature or fall within the predetermined allowable temperature range before or immediately after the temperature control unit starts temperature control.

4. The time-of-flight mass spectrometer according to claim 1, wherein the prediction unit predicts the possibility that the temperature of the flight tube will not reach the target temperature or fall within a predetermined allowable temperature range by comparing the difference between the ambient temperature and the target temperature with a predetermined judgment criterion value.

5. The time-of-flight mass spectrometer according to claim 1, wherein the prediction unit predicts the possibility that the temperature of the flight tube will not reach the target temperature or fall within the predetermined allowable temperature range, assuming that the temperature control unit operates within a range between a capacity that is a predetermined margin lower than the maximum capacity and a capacity that is a predetermined margin higher than the minimum capacity.

6. The time-of-flight mass spectrometer according to claim 1, further comprising a temperature control prediction unit that predicts the possibility of the flight tube temperature falling outside the target temperature or the allowable temperature range based on the ambient temperature, the target temperature, and the temperature of the flight tube, during temperature control execution by the temperature control unit after the temperature of the flight tube has reached the target temperature or fallen within the predetermined allowable temperature range, and the notification unit notifies the user according to the prediction result of the temperature control prediction unit.

7. The time-of-flight mass spectrometer according to claim 6, wherein the temperature control prediction unit predicts the time required until the temperature of the flight tube falls outside the target temperature or the allowable temperature range, and the notification unit notifies the user of the predicted time required.

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