JP2008157671A - Apparatus for estimating temperature, and time-of-flight mass spectrometer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To correctly grasp the shift in the mass axis of a mass spectrum, even if the ambient temperature changes sharply in the surrounding of a vacuum chamber that enclosed the flight tube, which is caused by this change, and where the user can find out if the shift deviates from the accuracy of the specifications of an apparatus. <P>SOLUTION: A step response of the shift of the mass axis is previously measured, when the temperature is changed in the vacuum chamber 1, in steps. A parameter that represents a transfer function, based on the response, is stored in the transfer function storage 21. A mass shift calculating section 22 estimates the current shift of the mass axis from the current temperature in the vacuum chamber 1, obtained by a second temperature sensor 24 and the transfer function stored in the storage 21, when an analysis is implemented. An abnormality determining section 23 determines whether the shift is within an acceptable range. When the shift exceeds acceptable range, an annunciation section 25 arouses the attention of the user. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a temperature estimation device that estimates the temperature of an object installed in a vacuum vessel having a vacuum atmosphere therein, and a time-of-flight mass spectrometer in which the object is a mass analyzer.

  In a time-of-flight mass spectrometer, various ions accelerated almost simultaneously by an electric field are introduced into the flight space formed in the flight tube, and the time required to fly through the flight space and reach the ion detector (flight time) The various ions are separated for each mass (strictly speaking, the mass-to-charge ratio m / z). Since the ion detector can continuously obtain detection signals according to the amount of ions that arrive, the flight spectrum is converted into mass, and then a mass spectrum is created with the horizontal axis representing the mass axis and the vertical axis representing the signal intensity axis. can do.

  In the time-of-flight mass spectrometer as described above, the flight distance of ions slightly changes when the flight tube temperature changes and mechanically expands or contracts. Then, the time of flight for ions having the same mass changes, so that the mass axis of the mass spectrum shifts. And if the temperature change of a flight tube is large, there exists a possibility that the shift | offset | difference of a mass axis may exceed the mass accuracy on the specification defined for the apparatus. Therefore, in a conventional time-of-flight mass spectrometer, a vacuum chamber in which a flight tube is installed is installed in a thermostatic chamber (temperature control housing), and the temperature change of the flight tube is reduced by controlling the temperature of the vacuum chamber. (See, for example, Patent Documents 1 and 2).

  However, in such a time-of-flight mass spectrometer, even if the temperature of the vacuum chamber is adjusted, the temperature control of the vacuum chamber is disturbed due to a sudden change in the outside air temperature, and as a result, the mass axis is shifted. There is a case. For this reason, it is necessary to estimate the amount of deviation of the mass axis by some method, and to alert the user when the amount of deviation exceeds the allowable range.

  A suitable method for estimating the amount of deviation of the mass axis due to the above factors is a method of monitoring the temperature of the flight tube itself and estimating the amount of deviation of the mass axis from the monitored value. However, since a high voltage is normally applied as an electrode to the flight tube and it is placed in a vacuum atmosphere in the vacuum chamber, it is difficult to attach a temperature sensor to the flight tube itself and monitor its temperature. Therefore, in general, a temperature sensor is attached to a vacuum chamber exposed to air in a thermostatic chamber, the temperature is monitored, and the amount of deviation of the mass axis is estimated based on the monitored value.

  However, since heat is difficult to transfer in a vacuum, the actual temperature change of the flight tube causes a relatively large response delay with respect to the monitor temperature of the vacuum chamber. Therefore, if it is determined that the monitored value of the temperature sensor attached to the vacuum chamber is the temperature of the flight tube and the amount of deviation of the mass axis is determined, an erroneous determination may be made. As a result, the analysis results that actually cause a large mass deviation are adopted as high accuracy, or conversely, the results of mass analysis being performed with high accuracy are mistakenly determined to be incorrect and discarded. There is a possibility of doing.

JP 2004-170155 A JP 2006-140064 A

  The present invention has been made to solve the above-mentioned problems, and the object of the present invention is to provide a mass axis of a mass spectrum by the influence of a temperature change of a flight tube placed in a vacuum atmosphere to which a high voltage is applied. It is an object of the present invention to provide a time-of-flight mass spectrometer capable of accurately grasping the deviation.

  Another object of the present invention is that it is difficult to directly measure its own temperature because it is similarly installed in a vacuum atmosphere or a high voltage is applied. An object of the present invention is to provide a temperature estimation device that can estimate the temperature of a target object with high accuracy.

1st invention made in order to solve the said subject WHEREIN: In the temperature estimation apparatus which estimates the temperature of the target object installed in the vacuum vessel whose inside is a vacuum atmosphere,
a) temperature detecting means for detecting the temperature of the vacuum vessel;
b) storage means for storing a result of measuring in advance a thermal transfer function from the vacuum vessel to the object;
c) Estimating calculation means for estimating the current temperature of the object using the temperature of the vacuum vessel obtained by the temperature detection means and the transfer function stored in the storage means;
It is characterized by having.

  As described above, since heat conduction deteriorates in a vacuum, when the temperature of the vacuum vessel is changed suddenly (for example, to the extent that it can be regarded as a step), the change in the temperature of the object placed in the vacuum is There is a considerable time delay and the temperature change is slow (having a certain time constant). Therefore, the step response is experimentally measured in advance, and the thermal transfer function from the vacuum vessel to the object is obtained. However, since there is almost no individual difference between devices having the same structure in the transfer function, it is not necessary to measure the step response for each device, and the measurement results of the standard device can be used in other devices.

  The transfer function obtained above is a Laplace transform equation, which can be expressed as a digital filter (low-pass filter) having a certain time constant on a computer (that is, a discrete system). Specifically, the transfer function (Laplace transform equation) obtained in the experiment is converted into a discrete pulse transfer function (z transform equation) by bilinear z transformation, and the temperature of the vacuum vessel is calculated from the form of the obtained pulse transfer function. Is input, and the temperature of the object is output, and a discrete difference equation is derived. As a result, from the detection result of the temperature of the vacuum vessel, that is, without directly measuring the temperature of the object itself, the temperature of the object accurately reflecting the poor heat conduction in the vacuum can be accurately calculated. Can be estimated.

  When the object is a flight tube of a time-of-flight mass spectrometer, the temperature change of the flight tube appears as a deviation of the mass axis of the mass spectrum. Therefore, the time-of-flight mass spectrometer can estimate the amount of deviation of the mass axis using the same technique as the temperature estimation device according to the first aspect of the invention.

That is, the second invention made in order to solve the above-mentioned problem is configured by installing a mass analysis unit and an ion detector that form a flight space in which ions fly in a vacuum vessel whose inside is a vacuum atmosphere, Time-of-flight mass spectrometry for detecting a mass spectrum having a mass axis and an intensity axis based on the detection signal by detecting ions temporally separated according to mass by flying in a flight space. In the device
a) temperature detecting means for detecting the temperature of the vacuum vessel;
b) storage means for storing a result of measuring in advance a transfer function from a change in temperature of the vacuum vessel to a shift (change) in mass axis caused by a change in temperature of the mass analyzer;
c) using the temperature of the vacuum vessel at the current time obtained by the temperature detection means and a transfer function stored in the storage means, an estimation calculation means for estimating the degree of deviation of the mass axis at the current time;
It is characterized by having.

  In the time-of-flight mass spectrometer according to the second aspect of the invention, instead of measuring the step response of the temperature of the mass analyzer (flight tube) when the temperature of the vacuum vessel is rapidly changed in advance, the mass of the mass spectrum is measured. Measure the step response of the amount of axis deviation (change). In order to obtain the step response of the deviation amount of the mass axis, for example, ions of a specific mass are repeatedly subjected to mass analysis, and the mass obtained thereby can be traced. If the analysis conditions such as the ion acceleration voltage are different, the step response of the mass axis deviation amount is considered to change. Based on this, the step response of the mass axis deviation amount is obtained for each analysis condition. The transfer function may be stored in the storage means.

  The transfer function representing the relationship from the change in temperature of the vacuum vessel to the change in the mass axis is the same as in the case of the first invention described above. It can be expressed as a difference equation) with input and mass axis deviation (change) amount as output. As a result, from the detection result of the temperature of the vacuum vessel, that is, without directly measuring the temperature of the flight tube, the mass axis deviation amount accurately reflecting the poor heat conduction in the vacuum can be obtained with high accuracy. Can be estimated.

  As one aspect of the time-of-flight mass spectrometer according to the second aspect of the invention, a notification is made to notify the user when the deviation amount of the mass axis estimated by the estimation calculation means as described above exceeds a predetermined allowable range. It can be set as the structure further provided with a means. As the notification means, notification by display, notification by sound, and the like can be considered.

  According to this configuration, when the mass axis of the mass spectrum deviates so as to deviate from the mass accuracy on the specification of the apparatus during the analysis due to the influence of the temperature change, the user quickly recognizes the situation, for example, Appropriate measures can be taken, such as discarding the obtained results, temporarily suspending the analysis, or checking whether the apparatus is defective.

  According to the temperature estimation device according to the first aspect of the present invention, this is estimated with high accuracy without directly measuring the temperature of an object placed in a vacuum or to which a high voltage is applied. It becomes possible.

  Moreover, according to the time-of-flight mass spectrometer according to the second aspect of the present invention, the mass spectrum caused by the temperature change without directly measuring the temperature of the flight tube installed in the vacuum vessel and applied with a high voltage. It is possible to estimate the degree of deviation of the mass axis with high accuracy. As a result, it is possible to obtain an analysis result in a state where the deviation of the mass axis is always small. In addition, when the mass axis is abnormally shifted, the user can recognize it and take appropriate measures.

  A time-of-flight mass spectrometer that is one embodiment of the present invention will be described with reference to the drawings. FIG. 1 is a configuration diagram of a main part of a time-of-flight mass spectrometer according to this embodiment.

  The vacuum chamber 1 is evacuated by a vacuum pump 2 such as a turbo molecular pump capable of achieving a high vacuum. In this vacuum chamber 1, a flight tube 3, which is a tubular part that forms a flight space 4, is installed so as to be held by a holding member 9 made of a low thermal conductivity material (for example, ceramic or resin). . That is, the flight tube 3 is placed in a vacuum. A reflectron (ion reflector) 7 is installed at one end (right end in FIG. 1) of the flight tube 3, and an ion source 5, an ion accelerator 6 and an ion detector 8 are installed at the other end (left end in FIG. 1). Has been.

  Various configurations known as the ion source 5 such as a MALDI (Matrix Assisted Laser Desorption / Ionization) ion source, an LCMS ion source such as ESI / APCI, etc., and an ion trap that discharges ions after temporarily accumulating them. Can also be used. For example, in the case of ionization under substantially atmospheric pressure, such as an LCMS ion source, the ion source 5 is installed outside the vacuum chamber 1, and ions generated therein are introduced into the vacuum chamber 1 to be ion accelerator 6. It is accelerated by.

  The vacuum chamber 1 is housed in a thermostatic chamber (temperature control housing) 10. The thermostatic chamber 10 includes a fan 11, a heater 12, a first temperature sensor 13 that measures the temperature of air in the chamber, and the vacuum chamber 1. A temperature control device including a second temperature sensor (corresponding to a temperature detecting means in the present invention) 24 for measuring temperature is provided. This temperature control device is controlled by the temperature control unit 14 so that the temperature detected by the second temperature sensor 24 becomes a predetermined target temperature. Such a temperature control method is described in Patent Document 1 described above.

  The ion source 5, the ion accelerator 6, and the reflectron 7 are controlled by an analysis control unit 20 for performing mass analysis. A detection signal from the ion detector 8 is input to the data processing unit 15 where a mass spectrum is created. The temperature detected by the second temperature sensor 24 for detecting the temperature of the vacuum chamber 1 is also input to a mass deviation calculation unit (corresponding to estimation calculation means in the present invention) 22 included in the analysis control unit 20. . The mass deviation calculation unit 22 uses the detected temperature and the difference equation representing the transfer function stored in advance in the transfer function storage unit (corresponding to the storage means in the present invention) 21, and the mass spectrum at an arbitrary time point. The amount of deviation of the mass axis is estimated. The abnormality determination unit 23 determines the estimated amount of deviation of the mass axis, and if the amount of deviation exceeds the allowable range, the notification unit (corresponding to the notification unit in the present invention) 25 alerts the user. The alerting | reporting part 25 shall perform alerting by the sound of a display or a buzzer sound, for example.

  All or some of the functions of the analysis control unit 20 and the data processing unit 15 are realized by executing a calculation system program incorporated in the apparatus main body or a dedicated program installed in a personal computer. It can be constituted as follows.

  The basic mass analysis operation of the apparatus having the above-described configuration is as follows. That is, various ions generated by the ion source 5 are given kinetic energy by a predetermined acceleration voltage in the ion accelerator 6 and fly in the flight space 4 toward the reflectron 7. The ions are turned back by the gradient electric field formed by the reflectron 7, return to the flight space 4, reach the ion detector 8, and are detected. Since the time required for the ions to reciprocate in the flight space 4 depends on the mass of the ions (strictly, the mass-to-charge ratio), if various ions are accelerated by the ion accelerator 6 almost at the same time, they have different masses. The ions reach the ion detector 8 with a time difference. The ion detector 8 continuously detects the amount of ions reached (ion intensity), and the data processing unit 15 converts the flight time to mass based on the detection signal obtained by the ion detector 8 to create a mass spectrum. .

  When the flight tube 3 expands or contracts due to heat, the flight distance from the ion accelerator 6 and reflected by the reflectron 7 to reach the ion detector 8 changes. For example, as the flight distance becomes longer, the flight time becomes longer accordingly, so that the mass determined for the same type of ions is shifted in the direction of increasing on the mass axis of the mass spectrum. That is, the mass axis shifts. In this time-of-flight mass spectrometer, the temperature fluctuation of the flight tube 3 is suppressed by installing the vacuum chamber 1 in the thermostat 10 and maintaining the temperature of the vacuum chamber 1 as constant as possible (temperature adjustment). . However, for example, when the outside air temperature greatly fluctuates, the temperature of the vacuum chamber 1 fluctuates due to the influence of the disturbance, and the fluctuation is transmitted to the flight tube 3, and the temperature fluctuation of the flight tube 3 causes a deviation of the mass axis. Therefore, in this device, the mass deviation amount of the mass spectrum is estimated as follows, and when the deviation amount exceeds the allowable range (usually a range determined by the mass accuracy defined in the specification of the device), Notification is performed.

  The transfer function storage unit 21 provided in the analysis control unit 20 stores a transfer function measured in advance from the temperature change of the vacuum chamber 1 to the mass axis deviation amount. Specifically, the temperature of the vacuum chamber 1 is changed stepwise (in a form close to) by changing the temperature control setting value of the vacuum chamber 1 to a step shape using this device or another device having the same configuration. The step response of the deviation amount of the mass axis of the mass spectrum at that time is measured.

  When the temperature of the vacuum chamber 1 changes stepwise, the flight tube 3 is in a vacuum, so even if the temperature of the vacuum chamber 1 rises, the heat is completely transferred to the flight tube 3 and the temperature rises. Takes a long time, usually more than 2 hours. As the temperature of the flight tube 3 gradually rises and the flight distance changes, the mass axis of the mass spectrum shifts accordingly. This mass axis deviation correlates with the temperature change of the flight tube 3.

For example, in the case of an apparatus that regulates the temperature of the vacuum chamber 1 to 40 ° C., the temperature of the vacuum chamber 1 is normally changed from 37 ° C. to 40 ° C. or from 40 ° C. to 43 ° C. Step up to ℃. That is, in FIG. 2A, the temperature T0 before the change is 37 ° C. or 40 ° C., and the temperature T1 after the change is 40 ° C. or 43 ° C. At this time, it is specified for a predetermined period of time (that is, until the temperature of the vacuum chamber 1 is stabilized at a certain temperature to be changed to another certain temperature and stabilized for a while). By repeating the mass analysis of the ions of the mass and measuring the change in mass obtained in the data processing unit 15, the step response h (t) = dm / m _{meas of the} mass axis deviation amount as shown in FIG. (T) is acquired.

When the transfer function from the temperature change of the vacuum chamber 1 to the mass axis deviation is approximated by a delay time generally used as a thermal transfer function and a first-order lag system, the parameter of the transfer function is a dead time L ( Delay time from the time when the temperature of the vacuum chamber 1 changes to the time when the mass axis starts to change, and the conversion coefficient K (the mass when the vacuum chamber 1 is stable at the temperature T0) with respect to the temperature input. When the axis deviation is set to 0, it can be expressed by a conversion coefficient that represents how many ppm the mass axis changes when the temperature of the vacuum chamber 1 changes, and a time constant τ. That is, the transfer function is expressed by the following equation (1).
dM / M (s) = H (s) · X (s) = K · e ^−Ls · Y (s) = K · e ^−Ls · G (s) · X (s) (1)

Here, X (s) is the temperature x (t) of the vacuum chamber 1, dM / M (s) is a Laplace transform equation representing the mass axis displacement dm / m (t), and H (s) is the relationship between them. Represents the transfer function that connects. When the transfer function is expressed by a filter, L is simply an input delay (delay), and K is simply a conversion coefficient from a temperature change (° C.) to a mass axis change (ppm). As shown in equation (1), it is only necessary to design a first-order low-pass filter G (s) having a gain of 1 and a time constant τ, and the transfer function can be expressed by equation (3).
G (s) = 1 / (1 + τs) (2)
H (s) = K · e ^−Ls · G (s) (3)

When G (s) is applied to the temperature X (s) of the vacuum chamber 1, a temperature change amount Y (s) that is proportional to the mass axis deviation amount is obtained. That is, the following equation (4) is obtained.
Y (s) = G (s) · X (s) (4)

G (s) is converted into discrete G (z) by a bilinear z-transform expression expressed by the following equation (5).
s = (2 / T) · (1-z ⁻¹ ) / (1 + z ⁻¹ ) (5)
However, T is a sampling period.

The G (z) obtained by applying a conversion coefficient K from temperature to mass deviation and a delay L is a discrete system representation H (z) of H (s). Therefore, the following equations (6) and (7) are obtained.
G (z) = a (1 + z ⁻¹ ) / (1 + bz ⁻¹ ) (6)
However, a = 1 / (T + 2τ) and b = (T−2τ) / (T + 2τ).
H (z) = ^K.z -N.G (z) (7)
N is an integer part of L / T.

Equation (4) is expressed by the following equation (8) in discrete system expression. From the form of this equation, temperature sampling (every period T) of the vacuum chamber 1 (i = 1, 2, 3,..., K−1, k,...) at a certain time point k, the relationship between the temperature x [k] of the vacuum chamber 1 and the temperature change amount y [k] representing the mass axis misalignment amount at that time is expressed by the following equation (9): It can be expressed as a difference equation.
Y (z) = G (z) · X (z) (8)
y [k] = a (x [k] + x [k-1])-by [k-1] (9)

Instead of the input x [k] of this difference equation, x (k−N) delayed by time L (= N · T) is input, and the conversion coefficient between the temperature and the mass axis deviation amount is input to the output. By multiplying by K, the mass axis deviation dm / m [k] at the time point k can be obtained as shown in the following equation (10).
dm / m [k] = K {a (x [k-N] + x [k-N-1])-by [k-1]} (10)

In the above, for each of the parameters L, K, and τ, the temperature of the vacuum chamber 1 is used as an input, and a predicted value of the displacement amount of the mass axis is calculated using these parameters, and this calculated value (predicted value dm / m [ k]) and the actually measured mass axis deviation amount dm / m _meas (t) can be determined to be minimum. The transfer function parameters (L, K, τ) thus determined are stored in advance in the transfer function storage unit 21. Note that these parameters may be set in advance by the manufacturer that provides the apparatus, so that the user who uses the apparatus does not need to perform measurement for obtaining the parameters.

  When performing mass analysis in this time-of-flight mass spectrometer, the temperature detected by the second temperature sensor 24 attached to the vacuum chamber 1 is continuously given to the mass deviation calculation unit 22. The mass deviation calculation unit 22 uses the temperature monitor value and the parameters stored in the transfer function storage unit 21 to perform a series of calculation processes as described above, thereby calculating the current mass axis deviation amount. Can be estimated.

  The abnormality determination unit 23 determines whether or not the estimated value of the mass axis deviation amount obtained from moment to moment is within the allowable range. If the estimated value exceeds the allowable range, the notification unit 25 is driven, for example, by display Alert the user.

  For example, when the outside air temperature changes abruptly and the temperature of the air in the thermostatic chamber 10 changes abruptly, the temperature of the vacuum chamber 1 itself whose outer surface is exposed to the air also changes. On the other hand, although there is a long time delay until the temperature of the flight tube 3 in vacuum changes, the mass axis of the mass spectrum is shifted when the temperature of the flight tube 3 actually changes and the flight distance changes. Such a mass axis deviation is estimated by the mass deviation computing unit 22 as described above, and if a deviation that is large enough to deviate from the mass accuracy determined by the specifications of the apparatus is predicted, this is notified to the user. Therefore, at least the user can recognize that the accuracy of the mass axis of the analysis result (mass spectrum) obtained at that time is low.

  The above-described embodiment is an example of a time-of-flight mass spectrometer according to the present invention, and modifications and additions as appropriate within the scope of the present invention are included in the scope of the claims of the present application. For example, although the above embodiment has a reflectron type configuration, it is obvious that the present invention can be applied to a linear type.

  Moreover, although the said Example estimated the amount of mass axis deviations of the mass spectrum resulting from the temperature change of the flight tube 3 put in the vacuum, it is also possible to estimate the temperature of the flight tube 3 itself. it can. As one of the methods, the step response of the temperature of the flight tube 3 is actually measured in advance, instead of measuring the step response of the deviation amount of the mass axis when the temperature of the vacuum chamber 1 is changed stepwise. . In this case, a digital filter corresponding to the thermal transfer function G (s) from the vacuum chamber 1 to the flight tube 3 is designed by using Y (s) in the above description as a Laplace transform expression representing the temperature of the flight tube 3. The filter parameters may be stored in the transfer function storage unit 21.

  It is also clear from the above description that the temperature of the object placed in the vacuum atmosphere can be estimated by the same method, not the temperature of the flight tube 3.

The block diagram of the principal part of the time-of-flight mass spectrometer which is one Example of this invention. The figure which shows an example of the step-like change (a) of the step shape change of the temperature of a vacuum chamber, and the step response (b) of the deviation | shift amount of the mass axis of a mass spectrum with respect to it.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Vacuum chamber 2 ... Vacuum pump 3 ... Flight tube 4 ... Flight space 5 ... Ion source 6 ... Ion accelerator 7 ... Reflectron 8 ... Ion detector 9 ... Holding member 10 ... Constant temperature bath (temperature control housing)
DESCRIPTION OF SYMBOLS 11 ... Fan 12 ... Heater 13 ... 1st temperature sensor 14 ... Temperature control part 15 ... Data processing part 20 ... Analysis control part 21 ... Transfer function memory | storage part 22 ... Mass deviation calculation part 23 ... Abnormality determination part 24 ... 2nd temperature Sensor 25 ... notification unit

Claims (3)

In a temperature estimation device that estimates the temperature of an object installed in a vacuum vessel whose inside is a vacuum atmosphere,
a) temperature detecting means for detecting the temperature of the vacuum vessel;
b) storage means for storing a result of measuring in advance a thermal transfer function from the vacuum vessel to the object;
c) Estimating calculation means for estimating the current temperature of the object using the temperature of the vacuum vessel obtained by the temperature detection means and the transfer function stored in the storage means;
A temperature estimation device comprising: A mass analysis unit and an ion detector that form a flight space in which ions fly in a vacuum vessel having a vacuum atmosphere are installed, and are separated in time according to the mass by flying in the flight space. In a time-of-flight mass spectrometer that detects ions with the ion detector and obtains a mass spectrum having a mass axis and an intensity axis based on the detection signal,
a) temperature detecting means for detecting the temperature of the vacuum vessel;
b) storage means for storing a result of measuring in advance a transfer function from a change in temperature of the vacuum vessel to a shift (change) in mass axis caused by a change in temperature of the mass analyzer;
c) using the temperature of the vacuum vessel at the current time obtained by the temperature detection means and a transfer function stored in the storage means, an estimation calculation means for estimating the degree of deviation of the mass axis at the current time;
A time-of-flight mass spectrometer.   3. The time-of-flight mass analysis according to claim 2, further comprising notifying means for notifying a user when a deviation amount of the mass axis estimated by the estimation calculating means exceeds a predetermined allowable range. apparatus.

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