JPWO2019229942A1 - Time-of-flight mass spectrometer - Google Patents

Abstract

When the orthogonal acceleration flight time type mass analyzer in the Q-TOF mass analyzer repeats the measurement, the voltage control unit (42) synchronizes with the transport voltage control unit (43) with the trigger signal corresponding to the measurement cycle. The voltage control information is transmitted by serial communication, and the transport voltage control unit (43) reflects the voltage set value indicated by the received voltage control information in the actual voltage at the timing of the next trigger signal. On the other hand, during the measurement preparation period in which a predetermined voltage is applied to the ion guide in the collision cell to perform a residual ion elimination operation or the like for clearing the residual ions in the cell, the voltage control unit (42) is more than the measurement cycle. The voltage control information is sent in synchronization with the pseudo trigger signal having a short cycle, and the transport voltage control unit (43) actually sets the voltage set value indicated by the received voltage control information at the timing of the next pseudo trigger signal. Reflect in the voltage. As a result, even if the measurement preparation period is short, the residual ion elimination operation or the like can be reliably performed.

Description

The present invention relates to a time-of-flight mass spectrometer (hereinafter, appropriately referred to as "TOFMS"), and more particularly to a control system technology in TOFMS. The TOFMS according to the present invention is particularly suitable for an orthogonal acceleration type TOFMS (hereinafter, appropriately referred to as “OA-TOFMS”).

As one of the mass spectrometers, a quadrupole-time-of-flight mass spectrometer (hereinafter referred to as "Q-TOF mass spectrometer") is known. For example, the Q-TOF type mass spectrometer disclosed in Patent Document 1 includes an ion source for ionization by an electrospray ionization method, a tandem mass filter for selecting ions having a specific mass-to-charge ratio m / z, and the like. A collision cell for dissociating selected ions by collision-induced dissociation (CID), and OA-TOFMS having a orthogonal acceleration section, for product ions generated by dissociating ions derived from components in a sample. It is now possible to acquire high-precision, high-resolution mass spectra, that is, to perform MS / MS (= MS ² ) analysis. By using such a Q-TOF mass spectrometer as a detector for a liquid chromatograph, it is possible to sequentially detect components (compounds) separated in a column of a liquid chromatograph with high accuracy over time. it can.

In the Q-TOF type mass spectrometer as described above, an ion transport optical system that utilizes the convergence action of ions by a high-frequency electric field is used to transport ions to the subsequent stage, and ions that can pass through such an ion transport optical system are used. There is a principle limitation on the mass-to-charge ratio range of. Therefore, it is difficult to obtain a mass spectrum over a wide mass-to-charge ratio range by measurement by one ion injection. Therefore, in order to acquire a mass spectrum over a wide mass-to-charge ratio range, multiple measurements are performed while changing the high-frequency voltage applied to the ion transport optical system, and the different mass-to-charge ratio ranges obtained by each measurement are supported. A method of integrating mass spectrum data (hereinafter referred to as "m / z range scanning method") is known.

Further, when the collision energy for dissociating ions is changed in the collision cell of the Q-TOF type mass spectrometer, the dissociation mode is different even for the same precursor ion derived from the same compound, and the obtained mass spectrum (product ion spectrum) is obtained. ) Peak pattern is different. Therefore, by repeating the measurement for one target compound while changing the collision energy in multiple steps and integrating the mass spectrum data obtained in each measurement, more types of product ions can be observed. A method for creating a mass spectrum (hereinafter referred to as "CES (collision energy spread) method") is also known.

In both the m / z range scanning method and the CES method, one mass spectrum is created based on a plurality of mass spectrum data obtained by repeating the measurement by ion injection from the orthogonal acceleration unit a predetermined number of times. Therefore, the predetermined number of measurements can be regarded as one analysis unit. In that case, in the measurement of a predetermined number of times included in one analysis unit, it is necessary to switch the voltage applied to the ion transport optical system or the like for each measurement, that is, every time ions are ejected from the orthogonal acceleration unit. Therefore, in the control system circuit for controlling the measurement operation, if the control parameter that determines the voltage applied to the ion transport optics or the like is switched in synchronization with the periodic trigger signal for ion injection, reliable timing control is performed. It is convenient in that the control can be simplified while performing the above.

However, when the control synchronized with the periodic trigger signal for ion injection described above is performed, there are the following problems.

In the case of MS / MS analysis, if the ions derived from the component that was the subject of analysis in the analysis unit immediately before that remain in the collision cell, it may cause deterioration of the accuracy and quantitativeness of structural analysis. Become. As a method for removing residual ions, a method of applying a predetermined pulse voltage to the lens electrode on the inlet side or the outlet side of the collision cell is known as disclosed in Patent Document 2. Furthermore, as a method of eliminating the charge-up of the insulating structure holding the ion transport optical system, the quadrupole mass filter, etc., as disclosed in Patent Document 3, the ion transport optical system and the quadrupole mass filter A method of switching the voltage applied to the mass filter for a short time is known.

In order to maintain high analysis accuracy and analysis sensitivity, it is desirable to perform the above-mentioned residual ion elimination operation and charge-up elimination operation on a regular basis. Therefore, when the measurement is repeatedly carried out a plurality of times in one analysis unit as described above, it is preferable to carry out the residual ion elimination operation and the charge-up elimination operation in each analysis unit.

In order to perform the residual ion elimination operation and the charge-up elimination operation, it is necessary to switch the voltage applied to the ion transport optical system and the quadrupole mass filter by a procedure different from that at the time of normal measurement. However, in the conventional control described above, the voltage applied to each part is switched in synchronization with the measurement cycle, so that the measurement cycle determines the time required for the residual ion elimination operation and the charge-up elimination operation. Usually, it is necessary to reserve a longer measurement preparation time for such an operation than it actually takes to eliminate residual ions or eliminate charge-up. Therefore, assuming that the execution time of the analysis unit is the same as when the measurement preparation time is not provided, the time that can be allocated to the actual measurement by the measurement preparation time for performing the residual ion elimination operation and the charge-up elimination operation is provided. It becomes shorter, and the SN ratio and sensitivity may decrease. On the other hand, if the execution time of the analysis unit is lengthened by the amount of the measurement preparation time, the throughput of the analysis decreases, or the components in the sample introduced into the ion source are not analyzed, so to speak, the dead time becomes long, and the analysis Leakage may occur.

International Publication No. 2018/20600 Pamphlet Japanese Unexamined Patent Publication No. 2011-216425 International Publication No. 2014/181396 Pamphlet

In order to solve the above problems, it is necessary to shorten the measurement preparation time for the residual ion elimination operation and the charge-up elimination operation as much as possible, but this may complicate the control and increase the cost. Need to avoid.

The present invention has been made to solve these problems, and its main purpose is to shorten the measurement preparation time while avoiding complicated control, and to reliably eliminate residual ions and eliminate charge-up. It is to provide TOFMS which can carry out operation and the like.

The present invention made to solve the above problems is an ion source for ionizing a sample component and an ion for injecting an ion generated by the ion source or another ion derived from the generated ion into the flight space. A time-of-flight mass spectrometer comprising a time-of-flight mass spectrometer including an injection unit and one or more ion transport optical elements disposed between the ion source and the ion injection unit. A plurality of measurement operations in the time-of-flight mass spectrometer and a measurement preparation operation for normalizing the state of the ion passage path by applying a predetermined voltage to at least one of the one or more ion transport optical elements. In a time-of-flight mass spectrometer that repeatedly carries out the analysis unit including
a) A trigger signal generator that generates a periodic trigger signal for the operation of ejecting ions from the ion ejection unit.
b) A pseudo-trigger signal generator that generates a pseudo-trigger signal with a period shorter than the period of the trigger signal.
c) An injection voltage generating section that generates a voltage applied to the ion emitting section so as to eject ions from the ion emitting section in synchronization with the trigger signal.
d) Within the period of one analysis unit, during the measurement operation period, voltage control information is sent to the voltage generator described later at the timing synchronized with the trigger signal, while at least a part of the measurement preparation operation period. The voltage control unit sends voltage control information to the voltage generation unit described later at the timing synchronized with the pseudo trigger signal.
e) When the voltage control information is sent at the timing synchronized with the trigger signal, the voltage based on the voltage control information is synchronized with the trigger signal, and the voltage control information is the pseudo. When the voltage is sent at the timing synchronized with the trigger signal, the voltage based on the voltage control information is synchronized with the pseudo trigger signal, and each voltage is applied to each of the one or more ion transport optical elements. The transport voltage generator that is generated and
It is characterized by having.

In the present invention, the "ion transport optical element" means convergence, divergence, acceleration, deceleration, induction, etc. for ions by the action of a DC electric field, a high frequency electric field (AC electric field), or an electric field in which a DC electric field and a high frequency electric field are combined. It is an element that performs the operation of. Specifically, the ion transport optical element shall include an ion guide, an ion lens, an ion funnel, an ion deflector, a sampling cone, a skimmer cone, a quadrupole mass filter, a linear type or a three-dimensional quadrupole type ion trap, and the like.

Further, in the present invention, the "measurement preparation operation for normalizing the state of the ion passage path" can include at least one of the above-mentioned residual ion elimination operation and charge-up elimination operation.

Further, in the present invention, the "voltage control information" is information for determining a voltage value when the control target is a DC voltage, and at least an amplitude value or a frequency when the control target is a high frequency voltage (AC voltage). This is the information that determines one of the above.

Further, in the present invention, in order to reduce the number of signal lines between the voltage control unit and the transport voltage generation unit, or to reduce the number of LSI pins responsible for the control operation in the voltage control unit and the transport voltage generation unit. It is desirable that information and signals are exchanged between the voltage control unit and the transport voltage generation unit by serial communication according to a predetermined sequence.

In the present invention, during the measurement operation in which the time-of-flight mass analyzer performs measurement on ions, the voltage control unit performs the voltage corresponding to the measurement operation at the timing synchronized with the trigger signal received from the trigger signal generation unit. Send control information to the transport voltage generator. The transport voltage generator receives this voltage control information by serial communication, for example, and typically receives the voltage control information at the timing of the trigger signal immediately after the end of communication (that is, first generated after the end of communication). Is switched so as to be reflected in the voltage applied to each ion transport optical element all at once. Since the trigger signal is a signal that determines the timing of ion injection from the ion injection unit, the voltage generated by the transport voltage generation unit can be reliably changed for each measurement operation by the above processing.

On the other hand, during the measurement preparation operation, the voltage control unit responds to the measurement preparation operation at a timing synchronized with the pseudo trigger signal generated by the pseudo trigger generation unit, instead of using the trigger signal received from the trigger signal generation unit. Sends voltage control information to the transport voltage generator. In this case, the transport voltage generating unit switches the voltage so that the voltage control information is simultaneously reflected in the voltage applied to each ion transport optical element, for example, at the timing of the pseudo trigger signal immediately after the end of communication. The period of the pseudo-trigger signal is shorter than the period of the trigger signal. Therefore, during the measurement preparation operation period, the voltage applied to the ion transport optical element can be switched in a shorter cycle than during the measurement operation period. As a result, the operation of switching (or turning on / off) the voltage applied to the ion transport optical element multiple times for, for example, a residual ion removal operation or a charge-up elimination operation can be performed without waiting for the input of the next trigger signal. It can be completed in a shorter time. Therefore, in the present invention, the time required for the measurement preparation operation can be shortened as compared with the case where the voltage control information is sent to the transport voltage generating unit in synchronization with the trigger signal even during the measurement preparation period.

As one embodiment of the present invention, the transport control unit is a trigger signal selection unit that selectively sends the pseudo trigger signal or the trigger signal to the transport voltage generation unit, and during at least a part of the measurement preparation period. The configuration may include a switching control unit that switches the selection operation of the trigger signal selection unit so that the pseudo trigger signal is selected.

According to this configuration, in the transport voltage generation unit, the set value of the voltage based on the voltage control information sent from the voltage control unit is reflected in the actual output voltage according to the signal sent from the trigger signal selection unit. Since the circuit may be configured so as to be performed, the circuit configuration can be simplified.

According to the present invention, when performing a residual ion elimination operation, a charge-up elimination operation, or the like instead of an actual measurement, the ion transport optical element is specifically subjected to a period shorter than the measurement cycle, regardless of the measurement cycle. The applied voltage can be switched. As a result, the time required for the residual ion elimination operation and the charge-up elimination operation can be shortened as compared with the conventional case. As a result, it is not necessary to provide an unnecessarily long measurement preparation period for such operations while maintaining high measurement accuracy and sensitivity by reliably performing residual ion elimination operations and charge-up elimination operations. ..

Therefore, according to the present invention, even when the measurement preparation period is provided in one analysis unit, it is possible to secure a sufficient time for the actual measurement and perform the measurement with a high SN ratio and sensitivity. Further, since the measurement preparation time can be shortened, it is possible to avoid a decrease in analysis throughput, and shorten the dead time during which the components in the sample introduced into the ion source are not analyzed. For example, the TOFMS according to the present invention. Is used as an LC or GC detector, it is possible to avoid omission of analysis of components in the sample.

The schematic block diagram of the Q-TOF type mass spectrometer which is an Example of this invention. The block block diagram of the main part of the control system in the Q-TOF type mass spectrometer of this Example. The timing diagram for demonstrating the control operation in the Q-TOF type mass spectrometer of this Example. In the Q-TOF type mass spectrometer of this embodiment, the timing diagram which shows the period for executing the measurement operation and the measurement preparation operation in one analysis unit.

Hereinafter, a Q-TOF type mass spectrometer according to an embodiment of the present invention will be described with reference to the accompanying drawings.
FIG. 1 is a configuration diagram of a main part of the Q-TOF type mass spectrometer of this embodiment, FIG. 2 is a block configuration diagram of an analysis control unit, and FIG. 3 is a timing diagram for explaining a control operation.

The Q-TOF type mass spectrometer of this embodiment has a multi-stage differential exhaust system configuration, and in the chamber 1, an ionization chamber 2 having a substantially atmospheric pressure atmosphere and a second analysis having the highest degree of vacuum are provided. A chamber 6 and a first intermediate vacuum chamber 3, a second intermediate vacuum chamber 4, and a first analysis chamber 5 are provided in which the degree of vacuum increases in order from the ionization chamber 2 to the second analysis chamber 6.

The ionization chamber 2 is provided with an ESI spray 7 for performing ionization by an electrospray ionization (ESI) method, and when a liquid sample containing a target component (compound) is supplied to the ESI spray 7, the tip of the spray 7 is provided. Charged droplets are sprayed from the body, and ions derived from the target component are generated in the process of splitting the charged droplets and evaporating the solvent. The ionization method is not limited to this, and other ionization methods such as the atmospheric pressure chemical ionization method and the atmospheric pressure photoionization method may be used.

Various ions generated in the ionization chamber 2 are sent to the first intermediate vacuum chamber 3 through the heating capillary 8, converged by the array type ion guide 9 arranged in the first intermediate vacuum chamber 3, and passed through the skimmer 10. 2 It is sent to the intermediate vacuum chamber 4. Further, the ions are converged by the multipolar ion guide 11 arranged in the second intermediate vacuum chamber 4 and sent to the first analysis chamber 5. A quadrupole mass filter 12 and a collision cell 13 in which a multi-pole ion guide 14 is arranged are provided in the first analysis chamber 5.

Various ions derived from the components in the sample are introduced into the quadrupole mass filter 12, and at the time of MS / MS analysis, the ions having a specific mass-to-charge ratio according to the voltage applied to the quadrupole mass filter 12 are said to be. It passes through the quadrupole mass filter 12. This ion is introduced into the collision cell 13 as a precursor ion and dissociates by contact with the collision gas supplied in the collision cell 13 to generate various product ions. On the other hand, during normal mass spectrometry (MS ¹ analysis) without ion dissociation, the ions derived from the sample component pass through the quadrupole mass filter 12 almost as they are (however, the mass-to-charge ratio range actually passed is limited). The energy of the ions is reduced (that is, cooled) by contact with the collision gas introduced into the collision cell 13 and supplied into the collision cell 13.

Ions derived from sample components (non-dissociated ions and product ions generated by dissociation) are transported in the collision cell 13 while being converged by the action of an electric field formed by the multipolar ion guide 14. Then, the ions discharged from the collision cell 13 are guided by an ion guide 16 composed of a large number of disc-shaped electrodes arranged across the first analysis chamber 5 and the second analysis chamber 6, and the ion passage port 15 is used. It is introduced into the second analysis room 6 through the above. In the second analysis chamber 6, an orthogonal acceleration unit 17 which is an ion injection unit, a flight space 18 in which the reflector 19 is arranged, and an ion detector 20 are provided, and the orthogonal acceleration unit 20 is provided along the ion optical axis C. The ions introduced into 17 in the X-axis direction are ejected by being accelerated in the Z-axis direction at a predetermined timing. As shown by the alternate long and short dash line in FIG. 1, the ejected ions fly freely in the flight space 18 and then are turned back by the reflected electric field formed by the reflector 19, and then fly freely in the flight space 18 again to form the ions. Reach the detector 20.

The flight time from the time when an ion departs from the orthogonal acceleration unit 17 to the time when the ion reaches the ion detector 20 depends on the mass-to-charge ratio of the ion. The ion detector 20 outputs an ionic strength signal corresponding to the amount of incident ions every moment. The data processing unit 30 that receives the ionic strength signal includes a data collecting unit 31 and a mass spectrum integration processing unit 32 as functional blocks. The data collection unit 31 receives an ion intensity signal from the ion detector 20 and digitizes and stores the signal. The mass spectrum integration processing unit 32 creates a flight time spectrum based on the collected data, and creates a mass spectrum by converting the flight time into a mass-to-charge ratio. Further, the mass spectrum integration processing unit 32 integrates the mass spectrum having a limited mass-to-charge ratio range obtained in each measurement measured a plurality of times as described later, so that the mass spectrum has a wider mass-to-charge ratio range. To create. The term "measurement" as used herein refers to a cycle of acquiring an ion intensity signal over a predetermined flight time range corresponding to one ion injection.

An input unit 51 and a display unit 52, which are user interfaces, are connected to the integrated control unit 50, and the integrated control unit 50 receives instructions such as setting analysis conditions and starting analysis through such a user interface, and performs analysis conditions. The control information based on the analysis sequence is transmitted to the analysis control unit 40, and the analysis result and the processing result are displayed on the screen of the display unit 52. The analysis control unit 40 mainly performs the heating capillary 8, the array type ion guide 9, the skimmer 10, the multipolar ion guides 11 and 14, and the quadrupole mass filter 12 in order to execute the analysis under the control unit 50. , The ion transport optical element of the present invention, such as the ion guide 16, and the voltage applied to each part such as the orthogonal acceleration unit 17.

The integrated control unit 50 is usually a general-purpose personal computer or a computer called a higher-performance workstation, and its function is realized by executing the pre-installed dedicated control software on the computer. Can be.

As shown in FIG. 2, the analysis control unit 40 includes a reference signal generation unit 41, a voltage control unit 42, a transport voltage control unit 43, a transport power supply unit 44, an injection voltage control unit 45, an orthogonal acceleration power supply unit 46, and the like. In FIG. 2, one transport voltage control unit 43 and one transport power supply unit 44 are shown, but the transport voltage control unit 43 and the transport power supply unit 44 correspond to the components to which the voltage is applied, respectively. Alternatively, each of such components is provided corresponding to a group in which a plurality of such components are grouped together.

As a functional block for performing the control characteristic of the Q-TOF type mass spectrometer of this embodiment, the reference signal generation unit 41 includes the trigger signal generation unit 411, and the voltage control unit 42 includes the voltage indicator unit 421 and the trigger. The switching instruction unit 422, the pseudo trigger generation unit 423, the trigger selection unit 424, and the communication control unit 425 are included, the transport voltage control unit 43 includes the communication control unit 431 and the voltage setting unit 432, and the injection voltage control unit 45 It includes a communication control unit 451 and a voltage setting unit 452.

Here, the above-mentioned functional blocks in the reference signal generation unit 41, the transport voltage control unit 43, and the injection voltage control unit 45, the pseudo trigger generation unit 423 in the voltage control unit 42, the trigger selection unit 424, and the communication control unit. Each functional block of the 425 is composed of a PLD (programmable logic device), that is, a hardware circuit. On the other hand, each functional block of the voltage indicator 421 and the trigger switching indicator 422 of the voltage control unit 42 is mainly composed of a CPU and its peripheral circuits (RAM, ROM, etc.). That is, the latter is a functional block embodied by executing the control software stored in the storage device built in or attached to the CPU by the CPU.

Next, an example of the analysis operation in the Q-TOF type mass spectrometer of this embodiment and the characteristic control at that time will be described.
Here, the case of performing the analysis by the above-mentioned CES method will be taken as an example. As already described, in the CES method, the measurement of the predetermined mass-to-charge ratio range is repeated while changing the collision energy when dissociating the ions in the collision cell 13 in a plurality of steps, and the spectral pattern obtained by each measurement is obtained. By integrating different mass spectra, a mass spectrum in which various product ions derived from one component are observed is created. Here, for convenience of explanation, the mass spectrum obtained by one measurement is simply referred to as a mass spectrum, and the mass spectrum obtained by integrating the mass spectra obtained by a plurality of measurements under different collision energies is referred to as an integrated mass spectrum.

FIG. 4 is a timing diagram during the analysis cycle for acquiring one integrated mass spectrum. The measurement is repeated a plurality of times (n times in this case) in one analysis cycle, the flight time spectrum data obtained in each of the n measurements is integrated, and the integrated mass is integrated from the flight time spectrum obtained by the integration. Find the spectrum. The collision energy is determined by the voltage difference between the DC bias voltage applied to the rod electrode of the quadrupole mass filter 12 and the DC bias voltage applied to the rod electrode of the ion guide 14. Therefore, the voltage applied to one or both of the quadrupole mass filter 12 and the ion guide 14 is switched so as to change the voltage difference in order to change the collision energy at each measurement in one analysis cycle.

A measurement preparation period is provided during one analysis cycle. No actual measurements are taken during the measurement preparation period, instead the good (in other words, ideal) behavior of the ions in the ion passage path from the ion source to the detector during the measurement. A process is performed to remove or reduce the obstacles to return the ion passage path to a good state. Specifically, such processing includes a residual ion elimination operation for removing ions remaining in the collision cell 13 after measurement, and a surface of a structure holding the rod electrode of the quadrupole mass filter 12. It includes a charge-up elimination operation that removes the accumulated charge, and the like.

In the residual ion elimination operation, for example, the collision cell 13 is formed by applying a predetermined DC voltage to a plurality of rod electrodes constituting the ion guide 14 and lens electrodes provided on the inlet side or the outlet side of the collision cell 13 for a short time. The movement of the ions remaining in the collision cell 13 is promoted to eliminate the ions from the collision cell 13 (see Patent Document 2). On the other hand, in the charge-up elimination operation, for example, a predetermined DC voltage is applied to a plurality of prerod electrodes included in the quadrupole mass filter 12 for a short time to promote the movement of the accumulated charge and eliminate the charge. (See Patent Document 3). Therefore, even during these various processes performed during the measurement preparation period, the voltage applied to at least one of the plurality of ion transport optical elements installed between the ion source and the orthogonal acceleration unit is switched. Is done.

When the user specifies a predetermined analysis condition in the input unit 51 and then gives an instruction to execute the analysis by the CES method, the integrated control unit 50 that receives this instruction analyzes the control information based on the specified analysis condition. It is sent to 40 to instruct the start of analysis based on control information. The control information includes information such as the time of one analysis cycle and the repetition cycle of measurement (time of one measurement) during one analysis cycle. Here, as an example, it is assumed that the measurement repetition period is 2 kHz, the time of one analysis cycle is 10 msec, and the time of measurement preparation is 1 msec.

In this case, the trigger signal generation unit 411 in the reference signal generation unit 41 generates a trigger signal whose cycle is 2 kHz, which is the repetition cycle of the measurement (see FIG. 3A). This trigger signal is input to the voltage control unit 42 and the orthogonal acceleration power supply unit 46. During the period during which the measurement is performed in one analysis cycle, the voltage indicator 421 in the voltage control unit 42 sends the ion transport optical element or the orthogonal acceleration unit 17 to each ion transport optical element or the orthogonal acceleration unit 17 for each measurement based on the given control information. The voltage value applied to each of the included electrodes is set in the communication control unit 425. As shown in FIG. 3B, the trigger selection unit 424 generates a pulse signal delayed by a predetermined time depending on the measurement cycle from the input trigger signal, and uses the signal as the selection trigger signal for the transport voltage control unit 43. And the injection voltage control unit 45. Further, in the voltage control unit 42, the communication control unit 425 converts the information including the voltage value set from the voltage indicator unit 421 into a format that can be transmitted and received by serial communication, and then generates the selection trigger signal. It is transmitted to the transport voltage control unit 43 and the injection voltage control unit 45 in synchronization with the timing, that is, in synchronization with the trigger signal.

As is well known, in serial communication, identification information that identifies the receiving side is added to the information (voltage control information) that should be received by different transport voltage control units and sent out in order, and the identification information is sent by the receiving side. By deciphering, a method is adopted in which it is determined whether or not the information is sent to itself and the necessary information is selectively received. Here, too, in the voltage control unit 42, the communication control unit 425 sequentially sends out four voltage control information, for example, Da, Db, Dc, and Dd, as shown in FIG. 3C, and a plurality of transport voltage control units. The communication control units 431 and 451 in the 43 and the injection voltage control unit 45 select and capture one of the four voltage control information by using the added identification information. As a result, during the period between one selection trigger signal and the next selection trigger signal, the plurality of transport voltage control units 43 and the injection voltage control unit 45 transmit and receive voltage control information necessary for setting the voltage. be able to.

In the voltage setting units 432 and 452 of the transport voltage control unit 43 and the injection voltage control unit 45, the voltage value indicated in the voltage control information received by the communication control units 431 and 451 is the timing of the selection trigger signal immediately after the communication. Change the voltage setting so that it is reflected in the actual voltage. Then, in response to this change in the set value, the transport power supply unit 44 and the orthogonal acceleration power supply unit 46 switch the output voltage (see FIG. 3E). Therefore, when the measurement is executed, the voltage applied to the ion guide or the like is switched at the timing of the selection trigger signal.

As described above, during the analysis by the CES method, the DC bias voltage applied to the rod electrode of the quadrupole mass filter 12 and the rod electrode of the ion guide 14 are used to change the collision energy stepwise for each measurement. Either or both of the DC bias voltage applied to the device is changed for each measurement. This DC bias voltage switching is also performed by transmitting and receiving voltage control information from the voltage control unit 42 to one of the plurality of transport voltage control units 43 as described above, and changing the voltage set value based on the received voltage control information. Will be done.

Thus, in n measurements in one analysis cycle, the collision energy of the ions introduced into the collision cell 13 is different for each measurement, and therefore the ions in contact with the collision gas in the collision cell 13 are different aspects. Dissociate with. Therefore, even if the mass-to-charge ratio of precursor ions is the same, the product ions produced are different. As a result, the pattern of the flight time spectrum based on the data collected by the data collection unit 31 is different for each measurement. When n flight time spectra for which n measurements have been completed are obtained, the mass spectrum integration processing unit 32 creates an integrated mass spectrum from the flight time spectra obtained by integrating the data.

On the other hand, when the measurement preparation period is entered after n measurements are completed, the pseudo-trigger generation unit 423 generates a pseudo-trigger signal having a predetermined period shorter than the measurement cycle, and the voltage control unit 42 generates a trigger switching instruction unit 422. Switches the trigger selection unit 424 so that this pseudo trigger signal is output as a selection trigger signal (see FIG. 3E). Since the period of this pseudo-trigger signal is meaningless unless it is significantly shorter than the measurement period, for example, when the measurement period is 2 kHz, the period of the pseudo-trigger signal may be set to, for example, 10 kHz.

During the measurement preparation period, the voltage indicator 421 in the voltage control unit 42 switches the voltage applied to the quadrupole mass filter 12, the ion guide 14, etc. in a predetermined procedure for the residual ion elimination operation and the charge-up elimination operation. , The voltage value is set in the communication control unit 425 at a predetermined timing. At this time, the communication control unit 425 converts the information including the voltage value set from the voltage indicator 421 into a format that can be transmitted / received by serial communication as described above, and then synchronizes with the timing at which the selection trigger signal is generated. That is, it is transmitted to the transport voltage control unit 43 in synchronization with the pseudo-trigger signal (see FIG. 3 (f)). That is, at this time, the cycle (communication cycle) of sending and receiving voltage control information from the voltage control unit 42 to the transport voltage control unit 43 is 10 kHz, which is 1/5 of the 2 kHz communication cycle (same as the measurement cycle) during the measurement operation. (Frequency is 5 times).

In the voltage setting unit 432 of the transport voltage control unit 43, the voltage value indicated in the voltage control information received by the communication control unit 431 is the timing of the selection trigger signal (pseudo trigger signal) immediately after the communication, as in the case of measurement. Change the voltage setting value so that it is reflected in the actual voltage (see FIG. 3 (g)). Then, in response to this change in the set value, the transport power supply unit 44 switches the output voltage. Therefore, during this measurement preparation period, the voltage applied to the quadrupole mass filter 12, the ion guide 14, and the like is switched at the timing of the pseudo trigger signal. Therefore, since the voltage switching is performed at shorter time intervals, that is, more frequently than during measurement, the residual ion elimination operation and the charge-up elimination operation can be performed in a short time, for example, 1 msec is determined. It can be reliably performed during the measurement preparation period, and there can also be sufficient time margin to allow the voltage to settle to the voltage required for the first measurement of the next analysis cycle after performing such processing.

As described above, in the TOF type mass spectrometer of the present embodiment, voltage control information is sent from the voltage control unit 42 to the transport voltage control unit 43 by serial communication in the same communication cycle as the measurement cycle at the time of measurement, and the voltage is sent in the same cycle. The set value of the voltage indicated by the control information is reflected in the actual voltage. On the other hand, during the measurement preparation period for performing the residual ion elimination operation and the charge-up elimination operation, voltage control information is sent from the voltage control unit 42 to the transport voltage control unit 43 by serial communication in a communication cycle shorter than the measurement cycle. The set value of the voltage indicated by the voltage control information in the communication cycle can be reflected in the actual voltage.

For example, assuming that the voltage can be switched only in the same communication cycle as the measurement cycle even during the measurement preparation period, when the measurement cycle is 2 kHz, voltage control information is sent from the voltage control unit 42 to the transport voltage control unit 43. Then, it takes 0.5 msec until it is reflected in the actual voltage. Further, in general, since the transmission and reception of signals between the CPU including the voltage indicator 421 as a functional block and the PLD including the communication control unit 425 as a functional block are asynchronous, the voltage indicator 421 changes the voltage setting value. The time required for it to be reflected in the actual voltage may be up to 2 cycles, that is, 1 msec. In that case, if the measurement preparation period is 1 msec, it is not possible to secure the time to execute the residual ion elimination operation and the charge-up elimination operation.

On the other hand, in the Q-TOF type mass spectrometer of this embodiment, since the communication cycle is 10 kHz during the measurement preparation period, the CPU including the voltage indicator 421 as a functional block and the PLD including the communication control unit 425 as a functional block. Even if the transmission and reception of signals to and from are asynchronous, the time required from when the voltage indicator 421 changes the set value of the voltage until it is reflected in the actual voltage is within 0.2 msec at the maximum. As a result, when the measurement preparation period is 1 msec, at least 0.8 msec can be allocated to the time for executing the residual ion elimination operation and the charge-up elimination operation, so that the residual ion elimination operation and the charge-up elimination operation can be performed. It can be executed reliably.

The above-mentioned numerical values are merely examples, and the present invention is not limited thereto.

Further, the processing executed during the measurement preparation period is not limited to the residual ion elimination operation and the charge-up elimination operation exemplified in the literature, and even when the purpose is to eliminate the residual ion and charge-up elimination, they are described in those documents. It is not limited to procedures and processes.

Furthermore, since all of the above examples are examples of the present invention, points other than those described above are included in the claims of the present application even if they are appropriately modified, added, or modified within the scope of the present invention. It is clear that.

1 ... Chamber 2 ... Ionization chamber 3 ... 1st intermediate vacuum chamber 4 ... 2nd intermediate vacuum chamber 5 ... 1st analysis chamber 6 ... 2nd analysis chamber 7 ... ESI spray 8 ... Heating capillary 9 ... Array type ion guide 10 ... Skimmer 11, 14 ... Multipolar ion guide 12 ... Quadrupole mass filter 13 ... Collision cell 15 ... Ion passage 16 ... Ion guide 17 ... Orthogonal accelerator 18 ... Flight space 19 ... Reflector 20 ... Ion detector 30 ... Data processing Unit 31 ... Data collection unit 32 ... Mass spectrum integration processing unit 40 ... Analysis control unit 41 ... Reference signal generation unit 411 ... Trigger signal generation unit 42 ... Voltage control unit 421 ... Voltage instruction unit 422 ... Trigger switching instruction unit 423 ... Pseudo trigger Generation unit 424 ... Trigger selection unit 425, 431, 451 ... Communication control unit 43 ... Transport voltage control unit 432, 452 ... Voltage setting unit 44 ... Transport power supply unit 45 ... Injection voltage control unit 46 ... Orthogonal acceleration power supply unit 50 ... Integrated control Unit 51 ... Input unit 52 ... Display unit C ... Ion optical axis

Claims (3)

A time-of-flight mass spectrometer including an ion source for ionizing a sample component, an ion injection unit for injecting an ion generated by the ion source or another ion derived from the generated ion into the flight space, and the ion. A time-of-flight mass spectrometer comprising one or more ion-transporting optical elements disposed between the source and the ion-injecting unit, wherein the time-of-flight mass spectrometer performs a plurality of measurement operations. A time-of-flight mass spectrometer that repeatedly performs a measurement preparation operation that normalizes the state of the ion passage path by applying a predetermined voltage to at least one of the one or more ion transport optical elements, and an analysis unit that includes the measurement unit. In
a) A trigger signal generator that generates a periodic trigger signal for the operation of ejecting ions from the ion ejection unit.
b) A pseudo-trigger signal generator that generates a pseudo-trigger signal with a period shorter than the period of the trigger signal.
c) An injection voltage generating section that generates a voltage applied to the ion emitting section so as to eject ions from the ion emitting section in synchronization with the trigger signal.
d) Within the period of one analysis unit, during the measurement operation period, voltage control information is sent to the voltage generator described later at the timing synchronized with the trigger signal, while at least a part of the measurement preparation operation period. The voltage control unit sends voltage control information to the voltage generation unit described later at the timing synchronized with the pseudo trigger signal.
e) When the voltage control information is sent at the timing synchronized with the trigger signal, the voltage based on the voltage control information is synchronized with the trigger signal, and the voltage control information is the pseudo. When the voltage is sent at the timing synchronized with the trigger signal, the voltage based on the voltage control information is synchronized with the pseudo trigger signal, and each voltage is applied to each of the one or more ion transport optical elements. The transport voltage generator that is generated and
A time-of-flight mass spectrometer characterized by being equipped with. The time-of-flight mass spectrometer according to claim 1.
A time-of-flight mass spectrometer characterized in that transmission / reception of voltage control information between the voltage control unit and the transport voltage generation unit is performed by serial communication. The time-of-flight mass spectrometer according to claim 1.
The voltage control unit selects a trigger signal selection unit that selectively sends the pseudo-trigger signal or the trigger signal to the transport voltage generation unit, and the pseudo-trigger signal during at least a part of the measurement preparation period. A flight time type mass analyzer comprising a switching control unit for switching the selection operation of the trigger signal selection unit as described above.

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