Time-of-flight mass spectrometer

Abstract

According to one embodiment of the present invention, a TOFMS, which avoids the generation of useless time and achieves the efficiency of analysis work when appropriate temperature adjustment of a flight tube cannot be performed due to too low or too high room temperature, is provided with: an ion emission unit (142); a flight tube (144) that forms a space in which the emitted ions fly; a flight tube is arranged in the vacuum chamber (1); a temperature control unit (151) for controlling the temperature of the flight tube; and a temperature control unit (22) that controls the temperature control operation of the temperature control unit on the basis of the indirectly or directly measured temperature of the flight tube and a target temperature, the TOFMS being provided with: a temperature sensor (153) that measures the ambient temperature, which is the temperature outside the vacuum chamber; a prediction unit (23) that, on the basis of the ambient temperature and the target temperature, predicts the possibility that the temperature of the flight tube does not reach the target temperature or does not fall within a prescribed allowable temperature range including the target temperature even when the temperature is adjusted using the temperature adjustment unit; and reporting units (24, 4) for reporting to the user on the basis of the prediction results.

Description

Technical Field

[0001] This invention relates to a time-of-flight mass spectrometer (TOFMS). Background Technology

[0002] In Time-of-Flight (TOF) MS, ions of the analyte are typically given a constant kinetic energy in the ion ejection section and guided into a flight space formed within the flight tube, where they fly. The time required for the ion to travel a constant distance is then measured, and the mass-to-charge ratio (m / z) of the ion is calculated based on this flight time. Therefore, maintaining a constant flight distance is crucial for achieving high mass accuracy in TOF MS.

[0003] If the flight tube expands or contracts due to temperature changes, the flight distance will change, resulting in a decrease in mass accuracy. Therefore, in the TOFMS described in Patent Documents 1 and 2, the following configuration is adopted: a temperature control unit containing a heater is provided on the outside of the vacuum chamber that encloses the flight tube, and the flight tube is indirectly heated by the temperature control unit in such a way that the temperature of the flight tube detected directly or indirectly becomes the target temperature (45°C in the example described in Patent Document 2).

[0004] However, the heater's heating capacity is limited, so 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 previous TOFMS systems, the following countermeasure was adopted: the flight tube temperature was detected to see if it fell within the specified allowable temperature range that includes the target temperature. If the flight tube temperature did not fall within the allowable temperature range even after a specified time, a temperature adjustment error (timeout error) was displayed to alert the user.

[0005] Existing technical documents Patent documents Patent Document 1: International Publication No. 2019 / 224948 Patent Document 2: International Publication No. 2019 / 220497 Summary of the Invention The technical problem that the invention aims to solve Typically, vacuum chambers or flight tubes have very large heat capacities and large thermal time constants. Therefore, a considerable amount of time (e.g., tens of hours) is required from the start of temperature adjustment of the flight tube until the temperature reaches and stabilizes near the target temperature. Consequently, the time limit for determining a timeout error, as described above, is set quite long, and the indication of an excessively low or high ambient temperature due to a timeout error sometimes occurs tens of hours after the device has been started. In this case, the user waits futilely for an extended period, thus reducing the efficiency of the analysis operation.

[0006] This invention was made to solve such a technical problem, and its main objective is to provide a TOFMS that can properly adjust the temperature of the flight tube to ensure high quality accuracy and reduce the useless operation time associated with the temperature adjustment, thereby achieving high efficiency in the analysis operation.

[0007] Solution to the above technical problems One aspect of the present invention is a Time-of-Flight (TOF) system comprising: an ion ejection section; a flight tube forming a space for ions ejected from the ion ejection section to fly; a vacuum chamber containing the flight tube; a temperature control section for adjusting the temperature of the flight tube; and a temperature control section for controlling the temperature adjustment operation of the temperature control section based on indirectly or directly measured temperatures of the flight tube and a target temperature. The TOFMS comprises: A temperature sensor measures the temperature outside the vacuum chamber, i.e., the ambient temperature. The prediction unit, based on the ambient temperature and the target temperature, predicts the possibility that even with the temperature adjustment by the temperature control unit, the temperature of the flight tube will not reach the target temperature or fall within a specified permissible temperature range including the target temperature. The reporting department reports to the user based on the prediction results from the prediction department.

[0008] Invention Effects In the TOFMS solution described above by this invention, for example, in the initial stage of analysis preparation work such as before the start of temperature adjustment of the flight tube, if it is predicted that there is a high probability that the temperature of the flight tube will not fall into (reach) the allowable temperature range even after temperature adjustment by the temperature control unit, the reporting unit can report a warning to the user. Thus, according to this invention, the user can grasp the possibility that the temperature adjustment of the flight tube may not be performed properly at the initial stage of analysis preparation work, without having to wait a long time until the actual temperature change of the flight tube is determined. Moreover, in the event of such a possibility, appropriate measures can be taken quickly, such as adjusting the room temperature or changing the target temperature itself. Therefore, even in situations where the room temperature is too low or too high, useless time involved in the analysis can be avoided, the time spent on the analysis work can be shortened, and the efficiency of the analysis work can be improved. Attached Figure Description

[0009] Figure 1 This is a structural diagram of the main components of a Q-TOFMS as an embodiment of the present invention.

[0010] Figure 2 This is an example of a control flow diagram showing the temperature regulation start-up of the flight tube in the Q-TOFMS of this embodiment.

[0011] Figure 3This is a schematic diagram showing the relationship between room temperature and duty cycle used for heater control when the target temperature for temperature control of the flight tube is set to Ta.

[0012] Figure 4 This is a diagram showing the configuration of the part of a Q-TOFMS that is associated with the temperature control operation of the flight tube, as a variant.

[0013] Figure 5 This is a diagram illustrating an example of the control flow chart for temperature control of the flight tube in the Q-TOFMS of the above-described modified example. Detailed Implementation

[0014] The four-pole time-of-flight mass analysis device (Q-TOFMS), which is an embodiment of the TOSMS involved in the present invention, will be described with reference to the accompanying drawings.

[0015] In addition, in this embodiment, the TOFMS is a reflective TOFMS with orthogonal acceleration, but this is only one example. As will be described later, the present invention is not limited to orthogonal acceleration and is not limited to reflective TOFMS.

[0016] [The structure and general operation of Q-TOFMS] Figure 1 This is an overall configuration diagram of the Q-TOFMS according to this embodiment. The general structure and operation of the Q-TOFMS are shown below.

[0017] In this Q-TOFMS, an ionization chamber 10 is connected in front of the vacuum chamber 1. The interior 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. On the other hand, each chamber in the vacuum chamber 1 is evacuated by a suitable vacuum pump (not shown). Thus, this Q-TOFMS is configured as a multi-stage differential evacuation system in which the vacuum level increases in stages from the ionization chamber 10 in the order of the first intermediate vacuum chamber 11, the second intermediate vacuum chamber 12, the first analysis chamber 13, and the second analysis chamber 14.

[0018] An electrospray ionization (ESI) source 101 is disposed in the ionization chamber 10. The ESI source 101 charges a liquid sample supplied by a liquid chromatograph (not shown) and sprays it into the ionization chamber 10. Thus, the compounds in the liquid sample are ionized. However, the ionization method is not limited to this; ion sources based on other ionization methods, such as atmospheric pressure chemical ionization sources, atmospheric pressure photoionization sources, and probe electrospray ionization sources, can also be used.

[0019] The ionization chamber 10 and the first intermediate vacuum chamber 11 are connected by a narrow-diameter desolventizing tube 102. As described above, ions and fine charged droplets generated in the ionization chamber 10, originating from the sample components, are introduced into the desolventizing tube 102 and transported to the first intermediate vacuum chamber 11 by the pressure difference between the ionization chamber 10 and the first intermediate vacuum chamber 11. The desolventizing tube 102 is heated to a suitable temperature, and the charged droplets pass through the interior of the desolventizing tube 102, thereby promoting the vaporization of the solvent in the droplets and promoting the generation of ions.

[0020] A multi-polar ion guide 111 is disposed in the first intermediate vacuum chamber 11. Ions are converged near the ion optical axis C1 by the ion guide 111 and enter the second intermediate vacuum chamber 12 through the opening at the top of the cone-shaped body 112. A multi-polar ion guide 121 is also disposed in the second intermediate vacuum chamber 12. Ions are transported from the second intermediate vacuum chamber 12 to the first analysis chamber 13 through the ion guide 121.

[0021] The first analysis chamber 13 is equipped with a quadrupole mass filter 131 for separating ions based on m / z, a collision cell 132 with an ion guide 133 inside, and a pre-transfer electrode 134 for transporting ions ejected from the collision cell 132. Ions incident into the first analysis chamber 13 are guided into the quadrupole mass filter 131, and only ions with a specific m / z corresponding to the voltage applied to the quadrupole mass filter 131 pass through the quadrupole mass filter 131. Collision gases such as argon are continuously or intermittently supplied to the interior of the collision cell 132. Ions with a specified energy incident into the collision cell 132 come into contact with the collision gases and are dissociated through collision-induced dissociation, generating various product ions.

[0022] Various product ions ejected from the collision cell 132 are converged by the pre-stage transfer electrode 134 and transported to the second analysis chamber 14. The second analysis chamber 14 is equipped with a post-stage transfer electrode 141, an orthogonal acceleration section 142, a second acceleration electrode section 143, a flight tube 144, a reflector 145, a detector 148, etc. Ions, which have become a finer beam after passing through the post-stage transfer electrode 141, are accelerated in the orthogonal acceleration section 142 in a direction approximately orthogonal to the incident direction of the beam (in... Figure 1 The ions are emitted from the center (downward direction). The emitted ions are guided into the flight space 147 within the flight tube 144 via the second accelerating electrode 143. Through the flight tube 144 and the reflector 145, a [structure / structure] is formed within the flight space 147. Figure 1 The path shown in C2 creates an electric field that causes the ions to fly back. As a result, the ions fly back again and reach detector 148.

[0023] Ions emitted from the orthogonal acceleration section 142, which serves as the ion ejection section, travel at a velocity corresponding to the m / z of the ion. Therefore, various ions accelerated simultaneously are separated according to their m / z during flight and arrive at the detector 148 with a time difference. The detector 148 generates a detection signal in real time corresponding to the amount of ions arriving. A data processing unit (not shown) receiving this detection signal calculates the flight time based on the detection signal and generates a mass spectrum converting the flight time to m / z. Thus, a mass spectrum reflecting the structure of a specific compound in the liquid sample is obtained. Furthermore, in this Q-TOFMS, by allowing ions to pass directly through the quadrupole mass filter 131 without ion dissociation in the collision cell 132, a mass spectrum corresponding to the compound contained in the liquid sample can be obtained.

[0024] [Components related to temperature control of the flight tube] The flight tube 144 is disposed within a second analysis chamber 14 formed within a vacuum chamber 1. Specifically, the generally cylindrical flight tube 144, made of stainless steel or other metal, is mounted on the inner wall of the vacuum chamber 1 via multiple support members 146. A temperature regulating unit 151, including a heater (not shown), is installed on the outer wall of the vacuum chamber 1 for indirectly regulating the temperature of the flight tube 144. The temperature regulating unit 151 may be a component capable of cooling the flight tube 144, or it may be a component capable of both heating and cooling. Furthermore, the temperature regulating unit 151 may be configured to directly regulate the temperature of the flight tube 144, rather than indirectly. In this embodiment, there is one temperature regulating unit 151, but multiple temperature regulating units 151 may be provided, as in the device described in Patent Document 1.

[0025] A device temperature sensor 152 is installed on the outer wall of the vacuum chamber 1, at a location where a support member 146 is mounted. 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. Furthermore, an indoor temperature sensor 153, used to detect the ambient temperature at an appropriate distance from the vacuum chamber 1, is installed at an appropriate position on the outside of the vacuum chamber 1. The detection signal of this indoor temperature sensor 153 is also input to the control unit 2. Additionally, similar to the temperature control unit 151, multiple device temperature sensors 152 can be installed. Furthermore, the device temperature sensor 152 can also more directly detect the temperature of the flight tube 144. Multiple indoor temperature sensors 153 can also be installed.

[0026] The control unit 2 is typically composed of a computer, including a CPU, and comprises, as functional blocks, a target temperature setting unit 21, a temperature control unit 22, a temperature change prediction unit 23 when temperature adjustment is initiated, and a report processing unit 24. These functional blocks can be implemented by executing software (programs) mounted on the computer, but at least a portion of them can also be constructed using hardware circuitry such as a digital signal processor. Furthermore, the control unit 2 is connected to an input unit 3 and a report unit 4, which serve as a user interface. In addition to a display such as a visual reporter, the report unit 4 can also be a component such as a buzzer that provides audio or sound reports.

[0027] [Temperature adjustment mechanism of the flight tube] If the flight tube 144 expands or contracts due to heat during analysis, the flight distance of the ions changes, resulting in a mass error. To avoid this, in this Q-TOFMS, the temperature control unit 22, included in the control unit 2, controls the temperature adjustment operation of the temperature control unit 151 to maintain the flight tube temperature within a specified 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 calculated according to the detection signal from the device temperature sensor 152. Specifically, the power supplied to the heater included in the temperature control unit 151 is controlled by pulse width modulation (PWM), and the temperature control unit 22 controls the heating power by adjusting the duty cycle of the PWM control.

[0028] The target temperature is defined as a temperature appropriately higher than normal room temperature (ambient temperature). In the TOFMS of this embodiment, the standard target temperature is 42°C, and a variation of 0.5°C is considered permissible, with 42 ± 0.5°C (41.5 to 42.5°C) being the permissible temperature range. Hereinafter, 42°C is the default target temperature, and the target temperature can be changed within the specified temperature range through user operation of the input unit 3. The following explanation focuses on the case where the target temperature is 42°C, but as will be apparent from the explanation, the target temperature may not be 42°C.

[0029] When the device is in a stopped state or when the temperature adjustment unit 151 is not operating, the temperature of the flight tube 144 is approximately close to room temperature, which is far below the target temperature. Therefore, in order to perform the analysis, it is necessary to first start the temperature adjustment operation of the temperature adjustment unit 151 to bring the temperature of the flight tube 144 into the allowable temperature range. Figure 2 This is an example of a control flow diagram showing the temperature regulation start-up of the flight tube in the Q-TOFMS of this embodiment.

[0030] For example, if the user instructs the temperature adjustment to be started from the input unit 3 (step S1), the temperature change prediction unit 23 reads the detection signal from the indoor temperature sensor 153 and detects the current room temperature Tr (step S2). Next, the temperature change prediction unit 23 obtains the target temperature Ta information 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°C and the current room temperature Tr is 25°C, then the temperature difference ΔT = 17°C.

[0031] The larger the temperature difference ΔT, the greater the heating power required by the temperature control unit 22 to supply to the temperature regulation unit 151 in order to bring the temperature of the flight tube 144 closer to the target temperature Ta. However, there is a limit to the amount of heating power that can be supplied. Therefore, if the temperature difference ΔT is too large, even if the maximum heating power is supplied to the temperature regulation unit 151, the temperature of the flight tube 144 will not reach the allowable temperature range. Conversely, when the device is started, even without heating based on the temperature regulation unit 151, the temperature of the flight tube 144 will rise to a certain extent due to heat from various components. Therefore, if the temperature difference ΔT is too small, even without activating the temperature regulation unit 151, the temperature of the flight tube 144 may sometimes exceed the allowable temperature range. Therefore, when the temperature regulation is started, the temperature change prediction unit 23 determines whether the temperature difference ΔT exceeds 27°C (step S4). If it does not exceed 27°C, it then determines whether the temperature difference ΔT is below 6°C (step S6). Step S4 is a process of determining whether the room temperature is too low relative to the target temperature, and step S6 is a process of determining whether the room temperature is too high relative to the target temperature.

[0032] Here, the method for determining the temperature criteria of "27℃" and "6℃" in steps S4 and S6 will be explained.

[0033] Figure 3 This is a rough diagram showing the relationship between room temperature and the duty cycle in the PWM control of the heater, when the target temperature for the temperature regulation of the flight tube 144 is set to Ta, obtained through experiments. When the duty cycle is 100%, the heating power is full; when the duty cycle is 0%, the heating power is zero. Figure 3 As shown, 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 the heating power is adjusted at 100% duty cycle, i.e., full power. If the room temperature is below this, the temperature of the flight tube 144 cannot reach the target temperature Ta even when the heating power is adjusted at full power.

[0034] However, when controlling the supply of heating power to the heater in a state where the duty ratio is close to 100% or 0%, there is a risk that the followability of temperature change control decreases, the temperature stability of the flight tube 144 decreases, and the quality stability in analysis also decreases. Therefore, here, a margin for ensuring temperature stability is estimated to be 20%, the appropriate duty ratio range is considered to be 20% - 80%, and the room temperature range that can appropriately adjust the temperature of the flight tube 144 is set as TL - Th.

[0035] As an example, when the target temperature Ta is set to 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 determined as the determination criterion in step S4, and Ta - Th = 6°C is determined as the determination criterion in step S6. Of course, when the target temperature Ta is different, the determination criterion of the temperature difference △T can also be determined by the same method. However, the estimation of the margin of the duty ratio of PWM control is not limited to the above description, and in addition, it can be easily imagined that the method of determining the determination criterion is different due to the heating control method of the temperature adjustment unit 151. That is, the determination process in step S4 only needs to be a process for predicting the situation that the temperature of the flight tube 144 will not reach the allowable temperature range even through appropriate temperature adjustment, and the determination process in step S6 only needs to be a process for predicting the situation that the temperature of the flight tube 144 will exceed the allowable temperature range even through appropriate temperature adjustment.

[0036] In any case, when the determination in steps S4 and S6 is "Yes", it means that there is a high possibility that the temperature of the flight tube 144 will not converge to the allowable temperature range suitable for analysis even if the temperature adjustment based on the temperature adjustment unit 151 is implemented.

[0037] In addition, the determination process in step S4 is a determination based on the inequality "Ta - Tr > 27", so even if this formula is deformed and a determination based on the formula "Ta - 27 > Tr" is performed, it is obviously substantially the same. Similarly, even if a determination based on the formula "Ta - 6 < Tr" is performed, the determination process in step S6 is also substantially the same.

[0038] If the determination in step S4 is "Yes", the report processing unit 24 outputs a warning report indicating that the ambient temperature of the device is too low through the reporting unit 4 (step S5). In addition, if the determination in step S6 is "Yes", the report processing unit 24 outputs a warning report indicating that the ambient temperature of the device is too high through the reporting unit 4 (step S7). On the other hand, when the determination in step S6 is "No", it can be inferred that the ambient temperature is appropriate, so the process ends without performing the above-mentioned warning report at the start of temperature adjustment.

[0039] As a warning report in step S5, more specifically, a warning can be issued via display or sound: "The ambient temperature around the device is too low, therefore the flight tube temperature may be unstable. Please raise the room temperature to above X°C, or lower the target temperature to below Y°C." Furthermore, as a warning report in step S7, more specifically, a warning can be issued via display or sound: "The ambient temperature around the device is too high, therefore the flight tube temperature may be unstable. Please lower the room temperature to below X°C, or raise the target temperature to above Y°C."

[0040] Users who receive the warning report described above can adjust the room temperature, for example, by adjusting the air conditioner in the room where the Q-TOFMS is located. Previously, it was unknown whether the temperature of the flight tube 144 had fallen within the allowable temperature range at the time of temperature adjustment initiation. Users would only realize the room temperature was inappropriate after several tens of hours had passed since the temperature adjustment was initiated and a timeout error occurred. In contrast, with the Q-TOFMS of this embodiment, it is possible to know immediately after temperature adjustment initiation that the temperature of the flight tube 144 is likely not within the allowable temperature range. Therefore, unnecessary waiting time is not wasted, and malfunctions caused by excessively low or high room temperatures can be quickly eliminated. Furthermore, analysis can be performed even after several tens of hours since the temperature adjustment was initiated, provided that the temperature of the flight tube 144 has reliably fallen within the allowable temperature range.

[0041] Users who receive the warning report mentioned above can adjust the target temperature Ta from input unit 3 instead of adjusting the room temperature, thereby substantially reducing or increasing the temperature difference ΔT. However, if the target temperature is changed from the default value (42°C in this case), the flight distance changes compared to the case where the temperature of the flight tube 144 is the default value. If the flight distance changes, the relationship between the ion's flight time and the m / z value changes, so it is usually necessary to re-acquire mass calibration data by performing an actual measurement using a standard sample. It is also possible to perform mass calibration using pre-determined mass calibration data or mass calibration data provided by the device manufacturer without performing such an actual measurement, but in cases where high-precision analysis is required, it is preferable to acquire the measured mass calibration data as close as possible to the actual measurement of the target sample. Therefore, considering the time required to acquire such mass calibration data, it is desirable to adjust the room temperature without changing the target temperature Ta.

[0042] If the temperature adjustment is initiated as indicated above, the temperature change prediction unit 23 will be activated during the temperature adjustment start-up. Figure 2 In the parallel processing shown, the temperature control unit 22 initiates the temperature adjustment operation of the temperature adjustment unit 151 based on the detection signal from the device temperature sensor 152 and the target temperature Ta. Therefore, within a few tens of hours from the start of temperature adjustment, the temperature of the flight tube 144 reliably converges to the allowable temperature range, becoming a state where analysis can be performed.

[0043] Additionally, there may be situations where the problem is not related to room temperature or target temperature settings, but rather to a malfunction in the temperature control unit 151, preventing the temperature of the flight tube 144 from reaching the vicinity of the target temperature. Therefore, in the Q-TOFMS of this embodiment, it is preferable to equip it with the following functions found in conventional devices: detecting whether the flight tube temperature falls within a specified allowable temperature range including the target temperature; displaying a temperature control error if the flight tube temperature deviates from the allowable temperature range for a certain period of time; and displaying an indication that analysis is possible if the flight tube temperature converges within the allowable temperature range.

[0044] Furthermore, in the above description, only a warning report is issued to prompt the user to eliminate the fault when the ambient temperature is determined to be too high or too low. However, it is also possible to more actively perform the fault elimination action. Specifically, if the determination is "yes" in steps S4 and S6 above, the target temperature Ta can be automatically changed according to the room temperature at that time. As an example, as described in Patent Document 2, the target temperature Ta can also be changed to a temperature calculated by adding (or subtracting) a certain value to the detected room temperature (ambient temperature) when cooling is performed by the temperature control unit 151. However, as mentioned above, it is generally desirable to reacquire quality correction data when changing the target temperature, so the target temperature can be changed automatically and a change report can be issued.

[0045] [The structure and operation of a variant of Q-TOFMS] Next, refer to Figure 4 , Figure 5 A variation of the Q-TOFMS described above will be explained. Figure 4 This is a configuration diagram of the part of the Q-TOFMS associated with the temperature control operation of the flight tube, which is a modified example. Figure 5 This is an example diagram illustrating the control flow chart for temperature control of the flight tube in a modified Q-TOFMS. Figure 4 In the middle, in the Figure 1 The internal structure of vacuum chamber 1 in the Q-TOFMS shown is completely omitted, and the following is a description of the process. Figure 1 The same or equivalent constituent elements shown are labeled with the same reference numerals.

[0046] In this modified Q-TOFMS, the room temperature is detected at the start of temperature control, similar to the embodiment described above. Based on this room temperature and the target temperature, it is immediately predicted after temperature control is initiated whether the temperature of the flight tube 144 will fall into the allowable temperature range through the temperature control operation. In addition, in this modified Q-TOFMS, the possibility of the temperature of the flight tube 144 deviating from the allowable temperature range is continuously predicted during temperature control.

[0047] like Figure 4 As shown, in this modified Q-TOFMS, the control unit 2 further includes a temperature regulation model information storage unit 25 and a temperature variation prediction unit 26 as functional blocks. The temperature regulation model information storage unit 25 stores a pre-generated temperature regulation model function. The temperature regulation model function is a model function that predicts the time-varying temperature of the flight tube 144 using 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 device manufacturer using a multivariate analysis method. The temperature regulation model function, the detection signal of the room temperature sensor 153, the target temperature Ta of the target temperature setting unit 21, and the detection signal of the device temperature sensor 152 are input from the temperature regulation model information storage unit 25 to the temperature variation prediction unit 26, and its output is input to the report processing unit 24.

[0048] As described above, under the control of the temperature control unit 22, the flight tube 144 is conditioned by the temperature control unit 151 so that its temperature falls within the allowable temperature range centered on the target temperature Ta. During this temperature conditioning process, the temperature change prediction unit 26 reads the detection signal from the indoor temperature sensor 153 corresponding to the current room temperature Tr, and the 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, the temperature Tf of the flight tube 144 is predicted using a calculation formula obtained through prior experiments (step S13).

[0049] The temperature variation 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 time variation of the temperature of the flight tube 144. Then, based on the prediction results, it estimates the possibility that the temperature of the flight tube 144 may deviate from the allowable temperature range, and if there is a possibility of deviating, it estimates the time required until deviating (step S14).

[0050] If, in step S14, it is predicted that the temperature of the flight tube 144 may deviate from the allowable temperature range, and in step S15 it is determined to be "yes," the report processing unit 24 outputs a warning report from the report unit 4 indicating the predicted time required until the temperature deviates from the allowable temperature range and the existence of this possibility (step S16). Specifically, a warning such as "It is possible that the temperature will become outside the stable temperature range after X hours. Please change the target temperature or the room temperature" can be displayed. On the other hand, if in step S15 it is determined to be "no," then at least at that point in time, the temperature control of the flight tube 144 is not problematic, and therefore the process returns to step S11. By repeatedly performing the processes of steps S11 to S16, the possibility of the temperature of the flight tube 144 deviating from the allowable temperature range can be continuously monitored during the temperature control implementation, i.e., during the analysis execution.

[0051] Even if the temperature of the flight tube 144 temporarily falls within the allowable temperature range and stabilizes, if the room temperature drops or rises drastically during the analysis, for example due to the air conditioning stopping, the temperature of the flight tube 144 may deviate from the allowable temperature range after a certain period of time. In conventional devices, although a temperature control error occurs in such cases, it occurs after a considerable amount of time has elapsed since the room temperature change. This is because, as mentioned above, 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 devices, if the analysis is performed at the point when the temperature control error occurs, there is a risk that high-precision data cannot be collected.

[0052] In contrast, in this modified Q-TOFMS, even if the temperature of the flight tube 144 drops or rises drastically during the analysis while the temperature of the flight tube 144 is stable, and there is a risk that the temperature of the flight tube 144 might deviate from the allowable temperature range after several hours to tens of hours, the system will immediately report the potential deviation of the flight tube 144 temperature from the allowable temperature range along with the predicted time, based on the change in room temperature. Therefore, the user can take appropriate measures, such as adjusting the air conditioning to restore the changed room temperature. Alternatively, for example, the adjustment of the room temperature can be postponed if there is sufficient time to finish the analysis within the predicted time, or, in the case of continuous analysis of multiple samples, the number of samples can be adjusted to finish the analysis within the predicted time, allowing for planned and efficient analysis.

[0053] [Another variation] In the Q-TOFMS based on the above embodiments and variations, the device temperature sensor 152 is installed on the outer wall of the vacuum chamber 1 to indirectly detect the temperature of the flight tube 144, but the temperature of the flight tube 144 can also be detected more directly inside the vacuum chamber 1. Similarly, the temperature control unit 151 can also directly control the temperature of the flight tube 144 without going through the vacuum chamber 1.

[0054] Furthermore, either or both of the device temperature sensor 152 and the temperature control unit 151 can be provided not only individually, but also multiple times. When multiple device temperature sensors 152 and temperature control units 151 are provided, as described in Patent Document 1, it is possible to configure them such that, on the outer wall surface of the vacuum chamber 1 and along the axial direction of the flight tube 144 (in... Figure 1 Temperature sensors 152 and temperature control units 151 are installed at different positions (in the longitudinal direction) and / or at different positions on the outer wall of the vacuum chamber 1 in a plane orthogonal to the axis of the flight tube 144.

[0055] Of course, multiple indoor temperature sensors 153 can also be set, and the average value of the detected temperature of the multiple indoor temperature sensors 153 or other calculated values ​​can be set as the room temperature Tr.

[0056] Furthermore, TOFMS may not be Figure 1 The orthogonal acceleration method shown can also be configured, for example, to use an ion trap as the ion emission section and a matrix-assisted laser desorption / resorption ion source as the ion emission section. Furthermore, TOFMS is not limited to reflective types; any TOFMS that forms a flight space inside the flight tube and whose flight distance varies according to the temperature of the flight tube can be used in this invention.

[0057] Furthermore, the above-described embodiments and variations are merely examples of the present invention. Within the scope of the spirit of the present invention, any appropriate modifications, alterations, or additions to the present invention are obviously included within the scope of the claims of this application.

[0058] [Various solutions, their functions, and effects] Those skilled in the art should understand that the above exemplary embodiments are specific examples of the following solutions.

[0059] (Item 1) One embodiment of the TOFMS according to the present invention is a TOFMS comprising: an ion emission section; a flight tube forming a space for ions emitted from the ion emission section to fly; a vacuum chamber containing the flight tube; a temperature control section for adjusting the temperature of the flight tube; and a temperature control section for controlling the temperature adjustment operation of the temperature control section based on indirectly or directly measured temperature of the flight tube and a target temperature. The TOFMS comprises: A temperature sensor measures the temperature outside the vacuum chamber, i.e., the ambient temperature. The prediction unit, based on the ambient temperature and the target temperature, predicts the possibility that even with the temperature adjustment by the temperature control unit, the temperature of the flight tube will not reach the target temperature or fall within a specified permissible temperature range including the target temperature. The reporting department reports to the user based on the prediction results from the prediction department.

[0060] In the TOFMS described in item 1, for example, in the initial stage of analysis preparation work such as before the start of temperature adjustment of the flight tube, the prediction unit predicts, based on the actual ambient temperature and target temperature detected by the temperature sensor, the likelihood that the temperature of the flight tube will not fall within the specified allowable temperature range even if temperature adjustment is implemented using the temperature adjustment unit. This is, for example, in cases where the ambient temperature is extremely low or extremely high relative to the target temperature. If the prediction indicates a high probability that the temperature of the flight tube will not fall within the specified allowable temperature range, the reporting unit issues a warning report to the user.

[0061] According to the TOFMS described in item 1, users can anticipate the possibility that the flight tube temperature control may not be properly implemented at the initial stage of analysis preparation, without waiting for a long time until the actual temperature change of the flight tube is determined. Moreover, in the event of such a possibility, appropriate measures can be taken quickly, such as adjusting the room temperature or changing the target temperature itself. Thus, even in situations where the initial room temperature is too low or too high, unnecessary time involved in the analysis can be avoided, reducing the time spent on the analysis and achieving higher efficiency in the analysis process.

[0062] (Item 2) The TOFMS described in Item 1 can further include a target temperature setting unit, which changes the target temperature based on the prediction result of the prediction unit.

[0063] In the TOFMS described in item 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. Therefore, without adjusting the room temperature, the temperature of the flight tube can be brought to the target temperature or fall within the allowable temperature range by adjusting the temperature using the temperature control unit. Thus, high-quality and accurate analysis can be performed even when analysis is conducted in locations without room temperature control capabilities.

[0064] (Item 3) In the TOFMS described in Item 1 or Item 2, the prediction unit is able to predict the possibility that the temperature of the flight tube will not reach the target temperature or fall within the specified allowable temperature range before the temperature adjustment is performed by the temperature adjustment unit or after the temperature adjustment has just begun.

[0065] According to the TOFMS described in section 3, a warning is issued immediately after the device's temperature adjustment is initiated if the room temperature is too low or too high. Therefore, users can recognize that the room temperature is too low or too high with virtually no waiting time and take appropriate measures such as adjusting the room temperature. This allows for efficient analysis without incurring unnecessary waiting time.

[0066] (Item 4) In any of the TOFMS described in items 1 to 3, the prediction unit is able to predict the possibility that the temperature of the flight tube will not reach the target temperature or fall within the specified allowable temperature range by comparing the difference between the ambient temperature and the target temperature with a predetermined judgment benchmark value.

[0067] In the TOFMS described in item 4, through simple calculations, the likelihood of the flight tube temperature not reaching the target temperature or falling outside the permissible temperature range can be predicted with high accuracy. Therefore, the program (computer software) required to implement such a function can be simple, and the computer load can be relatively small.

[0068] (Item 5) In any of the TOFMS described in items 1 to 4, the prediction unit can be configured such that the temperature control unit assumes that the temperature control unit operates within a range between the capacity of the unit that is a specified margin lower than the maximum capacity and the capacity that is a specified margin higher than the minimum capacity, and predicts the possibility that the temperature of the flight tube will not reach the target temperature or fall within the specified allowable temperature range.

[0069] When the temperature control unit is driven by PWM control, its capability typically depends on the duty cycle of the PWM control. Therefore, the range of the temperature control unit's capability can be expressed as the range of the PWM control's duty cycle. Typically, the maximum capability is a 100% duty cycle, and the minimum capability is a 0% duty cycle. When the temperature control unit operates at or very close to its maximum capability, there is no margin of capability, making it difficult to cope with changes in ambient temperature, resulting in reduced temperature stability. This leads to a decrease in mass stability.

[0070] In contrast, in the TOFMS described in item 5, the temperature control unit does not operate when the duty cycle of the PWM control is close to 100% or 0%, thus achieving higher temperature stability and ensuring the quality stability during analysis.

[0071] (Item 6) The TOFMS described in any one of items 1 to 5 can be configured to further include a temperature regulation prediction unit, which, during the temperature regulation execution of the temperature regulation unit after the temperature of the flight tube reaches the target temperature or falls into the specified allowable temperature range, predicts the possibility that the temperature of the flight tube will deviate from the target temperature or from the allowable temperature range based on the ambient temperature, the target temperature, and the temperature of the flight tube, and the reporting unit reports to the user based on the prediction result of the temperature regulation prediction unit.

[0072] Even if the temperature of the flight tube is stabilized due to temperature control and analysis begins, if the room temperature changes significantly during the analysis, the temperature of the flight tube may still deviate from the allowable temperature range after a considerable period of time from that point.

[0073] In contrast, according to the TOFMS described in item 6, even if the flight tube temperature temporarily falls within the allowable temperature range, a warning report is quickly issued when the room temperature fluctuates significantly and the flight tube temperature is likely to deviate from the allowable temperature range. This allows users to quickly take appropriate measures, such as checking the room temperature. Furthermore, it avoids performing analyses when the flight tube temperature is outside the allowable temperature range, preventing the execution of low-precision and useless analyses.

[0074] (Item 7) In the TOFMS described in Item 6, it can be configured such that the temperature prediction unit predicts the time required for the temperature of the flight tube to deviate from the target temperature or the allowable temperature range, and the reporting unit reports the predicted time to the user.

[0075] In the TOFMS described in item 7, when there is a possibility that the temperature of the flight tube may deviate from the permissible temperature range due to significant changes in room temperature during analysis, the time required until this state is reached, i.e., the time during which appropriate analysis can continue, is reported. Therefore, even when room temperature cannot be adjusted, appropriate measures can be taken, such as confirming whether the analysis has ended within the reported time or adjusting the number of samples to ensure the analysis ends within that time. As a result, useless analyses can be avoided, and efficient analytical work can be performed.

[0076] Explanation of reference numerals in the attached figures 1. Vacuum chamber 10 Ionization Chamber 11. First Intermediate Vacuum Chamber 12 Second Intermediate Vacuum Chamber 13 Analytical Laboratory 1 14. Analytical Laboratory No. 2 101 Electrospray Ionization (ESI) Source 102 Solvent Removal Tube 111, 121, 133 Ion Guiders 112 conical hole body 131 Quadruple Mass Filter 132 Collision Pool 134 Pre-stage transfer electrode 141 Post-transfer electrode 142 Orthogonal Accelerator 143 Second Acceleration Electrode Section 144 Flight Tube 145 Reflector 146 Support components 147 Flight Space 148 detectors 151 Temperature Control Section 152 Temperature sensor device 153 Indoor Temperature Sensor 2. Control Department 21 Target Temperature Setting Unit 22 Temperature Control Department 23 Temperature fluctuation prediction unit during temperature control startup 24 Reporting Department 25 Temperature Control Model Information Storage Unit 26 Temperature fluctuation prediction unit during temperature control 3 Input Section 4. Reporting Department.

Claims

1. A time-of-flight mass analysis device, comprising: an ion ejection section; a flight tube forming a space for ions ejected from the ion ejection section to fly; a vacuum chamber containing the flight tube; a temperature control section for adjusting the temperature of the flight tube; and a temperature control section for controlling the temperature adjustment operation of the temperature control section based on indirectly or directly measured temperatures of the flight tube and a target temperature, characterized in that... The time-of-flight mass analysis device includes: A temperature sensor measures the temperature outside the vacuum chamber, i.e., the ambient temperature. The prediction unit, based on the ambient temperature and the target temperature, predicts the possibility that even with the temperature adjustment by the temperature control unit, the temperature of the flight tube will not reach the target temperature or fall within a specified permissible temperature range including the target temperature. The reporting department reports to the user based on the prediction results from the prediction department.

2. The time-of-flight mass analysis device as described in claim 1, characterized in that, It further includes a target temperature setting unit that changes the target temperature based on the prediction result of the prediction unit.

3. The time-of-flight mass analysis device as described in claim 1, characterized in that, The prediction unit predicts the possibility that the temperature of the flight tube will not reach the target temperature or fall within the specified allowable temperature range before or after the temperature adjustment is performed by the temperature adjustment unit.

4. The time-of-flight mass analysis device as described in claim 1, characterized in that, The prediction unit predicts the likelihood that the temperature of the flight tube will not reach the target temperature or fall within the specified allowable temperature range by comparing the difference between the ambient temperature and the target temperature with a predetermined judgment benchmark value.

5. The time-of-flight mass analysis device as described in claim 1, characterized in that, The prediction unit assumes that the temperature control unit operates within a range between a capacity that is a specified margin lower than the maximum capacity and a specified margin higher than the minimum capacity, and predicts the possibility that the temperature of the flight tube will not reach the target temperature or fall within the specified allowable temperature range.

6. The time-of-flight mass analysis device as described in claim 1, characterized in that, The system further includes a temperature prediction unit that, during the temperature adjustment process of the temperature adjustment unit after the temperature of the flight tube reaches the target temperature or falls into the specified allowable temperature range, predicts the possibility that the temperature of the flight tube may deviate from the target temperature or from the allowable temperature range based on the ambient temperature, the target temperature, and the temperature of the flight tube. The reporting unit then reports to the user based on the prediction results of the temperature prediction unit.

7. The time-of-flight mass analysis device as described in claim 6, characterized in that, The temperature control prediction unit predicts the time required for the temperature of the flight tube to deviate from the target temperature or the allowable temperature range, and the reporting unit reports the predicted time to the user.

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