JP2011141954A - Multiple circuiting type flight time mass spectrometry - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a mass spectrometry using a multiple circuiting flight time mass spectrometer in which a proper calibration can be performed and measuring errors can be reduced. <P>SOLUTION: In the mass spectrometry, a time of flight at the circuiting of a plurality of kinds of ions of which the mass to charge ratio is already known and a calibration constant based on the time of flight before circuiting are used, thereby a proper calibration can be performed, and measuring errors can be reduced. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a multi-turn time-of-flight mass spectrometry method.

  Japanese Patent Laid-Open No. 2001-143655 discloses a multi-turn time-of-flight mass spectrometer (TOFMS). The multi-turn TOFMS extends the flight distance and increases the mass resolution by causing the charged particles (ions) to make multiple turns in the same orbit. However, in the multi-turn TOFMS, charged particles of various masses go around one orbit at the same time. For this reason, if the ion mass is m and the charge is z, particles having a small mass-to-charge ratio (m / z) may overtake molecules having a large m / z value in the orbit. Under these conditions, it is difficult to grasp the flight distance of ions that have reached the detector. For this reason, it is difficult to detect an unknown molecule particularly when the multi-circular TOFMS is used.

  In response to the above problem, Japanese Patent Application Laid-Open No. 2007-335368 discloses a multi-turn time-of-flight mass spectrometer having an ion gate upstream of a detector. The TOFMS disclosed in this publication selectively excludes only ions having a predetermined mass-to-charge ratio (m / z) by an ion gate.

  Japanese Patent Application Laid-Open No. 2005-79049 discloses a method for reconstructing a single-round frequency spectrum from a plurality of round-frequency mixed spectrums obtained by a multi-round time-of-flight mass spectrometer.

  Japanese Patent Laid-Open No. 2006-59739 discloses a multi-turn time-of-flight mass spectrometer (TOFMS) having an ion trap. In the multi-circular TOFMS disclosed in this publication, the mass range discharged from the ion trap and introduced into the multi-circular TOFMS is set within a mass range in which no overtaking occurs.

  Japanese Patent Application Laid-Open No. 2008-117546 discloses a multi-turn time-of-flight mass spectrometer (TOFMS) having ion deflection means. In the multi-turn TOFMS disclosed in this publication, the ion deflecting means forms a magnetic field or an electric field and disperses ions separated from the orbit in a direction orthogonal or oblique to the traveling direction according to the mass. Let

JP 2001-143655 A JP 2007-335368 A JP-A-2005-79049 JP 2006-59739 A JP 2008-117546 A

  In a conventional time-of-flight mass spectrometer (TOFMS), a plurality of ions whose mass-to-charge ratios are already known are made to fly, the time when they reach the detector are measured, and the relationship between the mass sequence and the time sequence is used. The relationship between flight time and mass-to-charge ratio was obtained. And the time of flight of the analysis target substance was applied to the relationship, and the mass-to-charge ratio was calculated | required by this. However, when this method is applied to a multi-turn time-of-flight mass spectrometer (TOFMS), there is a problem that a measurement error occurs.

  An object of the present invention is to provide a mass spectrometric method using a multi-turn time-of-flight mass spectrometer that can appropriately perform calibration and reduce measurement errors.

  In the present invention, calibration can be appropriately performed by using a calibration constant based on the flight time of multiple types of orbits of ions whose mass-to-charge ratios are already known and the flight time before the orbit. , Based on the knowledge that it is possible to provide a mass spectrometry method that can reduce measurement errors.

  The first aspect of the present invention relates to a mass spectrometric method using a multi-turn time-of-flight mass spectrometer that measures the mass-to-charge ratio of ions using a circular orbit. This method uses a first calibration constant represented by Equation 8 to be described later.

As will be described later, the first calibration constant is the flight time after the lap that is the flight time in two or more laps (m, n) of the first reference ion whose mass-to-charge ratio is already known. (T _m , t _n ) and the flight time (t ₀ ) before orbiting, which is the flight time when the first reference ions flew a distance that does not orbit the orbit. The first calibration constant is a constant related to the energy given to ions and the flight distance in a multi-turn time-of-flight mass spectrometer.

  The mass (mass-to-charge ratio) of the ion to be measured can be obtained by using this constant, the number of circulations N of the target ion, and the flight time t. For this reason, in the first aspect of the present invention, first, the flight time (t) when the ion to be measured makes N orbits of the orbit is obtained. In the present invention, the mass-to-charge ratio (mass) of ions to be measured is measured using the obtained t and the first calibration constant.

  The above method is an excellent method. On the other hand, if the mass-to-charge ratio of ions to be measured deviates greatly from that of the first reference ion described above, the mass spectrometry may not be performed correctly by the above method. I found out. This is considered to be caused by, for example, the situation of the ion source. Therefore, in a preferred embodiment of the present invention, in order to appropriately perform the mass spectrometry method described above, the range of mass to charge ratio is limited to a range where mass analysis can be performed accurately.

A preferred embodiment of the present invention uses a first calibration constant to calculate a fitting function that is a function of the mass-to-charge ratio (M _ref ) of the first reference ion and the flight time (t) after N laps. Ask. Then, using a second reference ion different from the first reference ion, the range of the mass-to-charge ratio of the ion that fits the fitting function is obtained. This second reference ion is an ion whose mass-to-charge ratio is already known. It is determined whether or not the obtained mass-to-charge ratio and time of flight of the second reference ions are within a predetermined range with respect to the fitting function. This operation is performed for a plurality of reference ions. In this method, ions not included in the predetermined mass-to-charge ratio range are excluded from the measurement system. The predetermined range means, for example, that the deviation from the graph is within ± 5% or ± 10% in the graph of the mass-to-charge ratio and the time of flight. The determination of the deviation may be made automatically using a computer. A method for excluding ions not included in the mass-to-charge ratio range from the measurement system can be achieved by using a known method. However, the present invention also proposes an ion exclusion method suitable for the above-described method.

  That is, the preferred multi-circular TOFMS of the present invention has a deflection electrode for excluding predetermined ions from the circular orbit in the circular orbit. And using this deflection | deviation electrode, the ion which is not contained in the range of the mass-to-charge ratio which can be measured with the precision calculated | required previously is excluded from a measurement system. Devices and methods for removing unwanted ions from the orbit using a deflection electrode are already known. In the present invention, known deflection electrodes and deflection methods can be used as appropriate.

  The first method for removing unnecessary ions from the orbit is as follows. That is, this method uses the deflection electrode to exclude ions having a small mass-to-charge ratio and ions having a large mass-to-charge ratio in this order. In this method, first, the electric field of the deflection electrode is increased (or turned on) until the first ion included in the obtained mass-to-charge ratio range passes through the deflection electrode. As a result, ions having a mass to charge ratio smaller than the obtained mass to charge ratio range are excluded from the orbit. Next, the electric field of the deflection electrode is weakened (or turned off) until the last ion included in the obtained mass-to-charge ratio range passes through the deflection electrode. Then, after the last ion included in the obtained mass-to-charge ratio range passes through the deflection electrode, the electric field of the deflection electrode is strengthened. Thereby, ions having a mass to charge ratio larger than the range of the mass to charge ratio are excluded from the orbit.

  By doing in this way, only the ion group which has a mass to charge ratio which has a desired range can be effectively left in an orbit. The optimum value of the incident voltage for introducing ions into the circuit varies depending on the mass of the ions. According to the present invention, since it is possible to divide each ion group, mass analysis can be performed with high accuracy with an appropriate incident voltage.

  A second method for removing unnecessary ions from the orbit is as follows. That is, this method uses the deflection electrode to exclude ions having a large mass-to-charge ratio and ions having a small mass-to-charge ratio in this order. In this method, first, ions having a mass-to-charge ratio smaller than the obtained mass-to-charge ratio range pass through the deflection electrode. Thereafter, ions having a mass-to-charge ratio within the determined mass-to-charge ratio pass through the deflection electrode. When the last ion included in the obtained mass-to-charge ratio range has passed through the deflection electrode, the electric field of the deflection electrode is increased. Thereby, ions having a mass-to-charge ratio larger than the obtained mass-to-charge ratio range are excluded from the orbit.

  Next, the electric field of the deflection electrode is increased until the ions in the range of the mass-to-charge ratio that has reached the deflection electrode after completing the circulation. Then, ions having a small mass-to-charge ratio that have returned to the deflection electrode after completing the circulation are excluded from the orbit. By doing in this way, only the ions included in the mass-to-charge ratio range that can be measured with high accuracy can be left in the circuit. It should be noted that the electric field of the circular electrode may continue to maintain its strength, or once the electric field is weakened, for example, when ions with a low mass-to-charge ratio that may exist in the system, such as hydrogen ions, reach the deflection electrode. May be strengthened again.

  A third method for removing unnecessary ions from the orbit is as follows. That is, this method uses the deflection electrode to exclude ions having a small mass-to-charge ratio and ions having a large mass-to-charge ratio in this order. This method is basically based on the same idea as the first method described above. However, in this method, it is necessary that the electric field generated by the incident electrode can affect the circular orbit.

  That is, the multi-turn time-of-flight mass spectrometer used in this method has an incident electrode for introducing ions into the orbit and a deflection electrode for excluding predetermined ions from the orbit. Then, the electric field of the incident electrode is increased until the first ion included in the obtained mass-to-charge ratio circles the orbit and reaches the incident position by the incident electrode. As a result, ions having a mass to charge ratio smaller than the obtained mass to charge ratio range are excluded from the orbit. The subsequent operation is the same as in the first method.

  A fourth method for removing unnecessary ions from the orbit is as follows. That is, this method uses two deflection electrodes. A multi-turn time-of-flight mass spectrometer used in this method includes a first deflecting electrode for removing ions having a mass to charge ratio smaller than the determined mass to charge ratio range from the orbit, and a determined mass to charge ratio. And a second deflection electrode for excluding ions having a mass-to-charge ratio larger than the range from the orbit. Since it has such a configuration, this TOFMS can exclude ions having a smaller mass-to-charge ratio and larger ions from the circular orbit than the range of the mass-to-charge ratio.

In a preferred embodiment of the present invention, the mass-to-charge ratio is divided for each segment, and the mass-to-charge ratio is measured for each segment. Here, let L _F be the flight when the first ion having a predetermined mass-to-charge ratio (M _F ) makes N orbits and flies to a certain point on the orbit. On the other hand, when a second ion having a mass-to-charge ratio (M _L ) different from that of the first ion orbits N-1 and flies to a certain point on the orbit, let L be _L. At this _time, dividing the mass-to-charge ratio from _{M F / M L = (L} F / L L) 2 to become such _{M F} in the range of _{M L.} Incidentally, the a _{M F} may be less than or equal to _{M F} above _{M L} and _{M L,} may be less than _{M F} or _{M L} than may be less than or equal to _{M F} greater than _{M L.} In an actual measurement system, measurement may be performed including 10% (or 5%) before and after the segment. I.e., the range of 0.9 M _F of 1.1 M _L, may determine the extent of 1.05 m _L from 0.95 M _F. That is, the measurement range may overlap between the previous segment and the next segment. Consistency can be checked by overlapping measurement ranges in this way. The divided mass to charge ratios to measure the mass-to-charge ratio for each segment to be included within the scope of the M _L from M _F. N is an integer of 1 or more. Any of the above-described methods may be adopted as a method for extracting only a certain mass-to-charge range (segment). The maximum mass-to-charge ratio of the next segment can be obtained by setting the maximum mass-to-charge ratio of the first segment as the minimum mass-to-charge ratio of the next segment. Thereafter, ions can be classified into a plurality of segments by performing the same arithmetic processing.

Next, a specific mode for classifying ions into a plurality of segments will be described. The following modes basically create segments based on the relational expression M _F / M _L = (L _F / L _L ) ² .

In mode 1-1, segments are sequentially obtained by using a mass head that is the minimum mass-to-charge ratio to be subjected to mass analysis and a predetermined number of rounds. If Sadamare a predetermined cycle number N, _{L F} and _{L L} are determined. If the mass head M ₁ is determined, the values after M ₂ can be obtained sequentially according to Equation 15. This operation can be segmented by obtaining the mass-to-charge ratio including the mass tail.

Mode 1-2 is obtained by using the value of the center of mass of the segment ((M _F + M _L ) / 2) and a predetermined number of turns. This mode is particularly useful when analyzing a limited range of ions. That is, Sadamare a predetermined cycle number N, _{L F} and _{L L} are determined. By specifying the mass center of the segment _{((M F + M L)} / 2), based on equation 14, the expression is obtained about _{M F} and _{M L.} Then, by solving two simultaneous equations can be obtained M _L from M _F is in the range of this segment.

Modes 1-3 determine the maximum number of laps using the mass head that is the minimum mass-to-charge ratio subject to mass analysis and the mass tail that is the maximum mass-to-charge ratio subject to mass analysis. , A single segment that specifies the maximum number of laps. L _F and L _L are functions of the number N of laps. On the other hand, L _F and L _L have a relationship of L _F = L _L + L _t . Here, L _t is the length of the orbit and is a measurable value. Thus, M _F, and if it is given that M _L, it is possible to obtain the maximum N satisfying the relationship of Equation 14. Then, by performing measurement using the maximum value of N, it is possible to perform mass spectrometry making the best use of the length of the orbit.

In mode 2, the segment specifies the mass head that is the minimum mass-to-charge ratio subject to mass analysis, the mass tail that is the maximum mass-to-charge ratio subject to mass analysis, and the number of laps. M _F / M _L = (L _F / L _L ) ² is a segment obtained sequentially based on the relationship of ² .

If the number of laps is specified, L _F and L _L have a certain value. Then, for example, if segmentation is started from the top of mass, M ₂ is obtained based on the relationship of M ₂ / M ₁ = (L _F / L _L ) ² . By repeating this operation until a larger mass to charge ratio than M _F, the segmentation can be achieved. Of course, segmentation may be achieved by repeating the calculation so that the mass-to-charge ratio becomes smaller from the end of the mass.

In mode 3, the segment includes the first segment obtained by using the value of the center of mass ((M _F + M _L ) / 2) of the certain segment and the first number of laps. There may be one first segment or two or more first segments. In addition, when there are two or more first segments, the centers of mass of the segments are different. On the other hand, when there are two or more first segments, the first number of laps may be the same or different.

  The mode 3 further includes the second segment obtained by using the mass start that is the minimum mass-to-charge ratio to be subjected to mass analysis, the second number of rounds, and the maximum mass to be subjected to mass analysis. One or both of the third segment obtained by using the mass tail that is the mass-to-charge ratio and the third circulation number are included.

  As a detector for a time-of-flight mass spectrometer, a high-speed type ETP (electron multiplier) or MCP (microchannel plate) is often used. These ETPs and MCPs have excellent sensitivity because the gain of captured electrons is high. However, if a large amount of charged particles enter ETP or MCP at a time, a large amount of secondary electrons are generated, so that the state becomes saturated and does not react for a while. Mass spectrometry, for example, has high sensitivity because it can be amplified by this electron multiplier even if one charged particle enters the detector. However, if there is a large amount of particles near the substance to be measured, ETP and MCP are saturated and an accurate measurement value cannot be obtained, so the amplification factor cannot be increased.

  Therefore, in a preferred embodiment of the present invention, ions are divided into segments according to the above-described method, and a detector or a digitizer is adjusted for each segment. Examples of this detector are ETP and MCP. Signal amplification may be performed on the detector side or by adjusting the amplification factor of the digitizer variable amplifier. That is, a preferred embodiment of the present invention adjusts either or both of the detector amplification factor and the digitizer amplification factor for each segment. In this way, by adjusting the detector amplification factor or digitizer amplification factor for each segment and removing charged particles outside the mass range to be measured, it is possible to prevent the measurement system from becoming saturated. Wide and sensitive mass spectrometry can be performed.

  The present invention uses calibration constants based on the flight times of multiple orbits of ions whose mass-to-charge ratio is already known, and the time of flight before the laps, so that appropriate calibration can be performed. Thus, it is possible to provide a mass spectrometry method that can reduce measurement errors.

FIG. 1 is a conceptual diagram of a multi-turn time-of-flight mass spectrometer. FIG. 2 shows an example of voltage in a method in which two pulses are applied to the deflection electrode and transmitted between the pulses. FIG. 3 shows an example of voltage in a method of transmitting desired ions by applying one pulse or two pulses to the deflection electrode. FIG. 4 is a diagram illustrating an example of a voltage when a particle having a small mass in the first round is excluded before the OFF timing of the incident electrode. FIG. 5 is a diagram illustrating an example of voltage when two pairs of deflection electrodes are used to remove particles having a small mass at the first electrode of the circular orbit and to remove particles having a large mass at the subsequent electrode. FIG. 6 is a diagram showing each point of the multi-turn time-of-flight mass spectrometer of FIG. FIG. 7 is a conceptual diagram illustrating the points P1 and P2. FIG. 8 is a block diagram of a system in which a programmable gain amplifier is inserted between the detector and the AD converter. FIG. 9 is a block diagram showing a system capable of setting the amplification factor of the detector in addition to the system of FIG.

  Hereinafter, the form for implementing this invention using an Example is demonstrated. The present invention is not limited to the examples described below. The present invention includes not only the embodiments described below but also those that can be appropriately modified within the scope obvious to those skilled in the art from the following embodiments. In addition, the references cited in this specification are incorporated in this specification by citation. Moreover, the description of all the related literature already known at the time of application can be taken into this invention.

1 is a diagram showing a conceptual diagram of a multi-turn time-of-flight mass spectrometer. A voltage for applying energy to ions is applied to the ion source 1. On the other hand, a rectangular voltage (incident voltage) for deflecting ions toward the circular orbit shown by the dotted line in FIG. A voltage for moving ions in a circular orbit is applied to the circular electrodes 4, 5, 6, and 7. A rectangular voltage for deflecting ions from the circular orbit to the detector 9 is applied to the emission electrode 3. The deflection electrode 8 is applied with a rectangular voltage (deflection voltage) for sufficiently separating ions on the orbit from the orbit. The incident electrode 2 and the outgoing electrode 3 have small holes at positions where the circular orbit of ions is not blocked.

The substance of mass m accelerated from the ion source 1 with the voltage V _acc is deflected by the incident electrode 2 and guided to the orbit. The ions guided to the circular orbit return to the incident electrode 2 through the circular electrodes 4, 5, 6 and 7. Before the ions return to the incident electrode 2, the voltage of the incident electrode 2 is reduced and the ions are allowed to pass through. A voltage is applied to the output electrode 3 after the ions fly around the orbit for an arbitrary time. Then, the ions flying on the orbit are successively deflected and guided to the detector 9.

Let L ₁ be the distance from a point a near the extraction opening of the ion source to an arbitrary point b near the incident electrode end. The distance from point b to c any point near the exit electrode end and L _2. Let L ₃ be the distance from point c to point b. Also the _L 2 + _{L 3} and _{L t.} Then, L _t is the circuit distance. The distance from point c to point e in the vicinity of the detector and L _4. The distance from the point c to the point d in the vicinity of the deflection electrodes and L _5. Each point indicates a fixed point in calculation. Therefore, the accuracy of the position of each point in the figure and the actual position is not important.

Calibration method of a multi-turn time-of-flight mass spectrometer Consider a case where a particle having a charge amount e and a mass M energized by voltage V is ejected from an ion source at time t = 0. The flight distance is L, the velocity of the particle is v, and the time t when the particle is observed by the detector is the observation time. Then, the general equation of motion and energy conservation law are expressed as follows.

  In the multi-turn TOFMS shown in FIG. 1, the observation time t of N turns can be expressed as follows using Equations 1 and 2.

Consider a particle having a charge amount e and a mass M _ref energized by an ion source at an acceleration voltage V _acc . The observation times at the detector when this particle makes a round orbit around n and m rounds are t _n and t _m , respectively. From Equation 3, t _n and t _m can be expressed as follows.

From Equation 4 and Equation 5

Since e is an elementary charge amount and m and n are integers, e, m and n can be easily estimated from the measurement results. Therefore, Equation 6 shows that when a particle having a known mass is measured, a voltage V _acc with L _t as a parameter can be obtained from the observed values of t _n and t _m .

Further, if the flight distance is L _c and the observation time is t ₀ when the orbit does not circulate and makes a half orbit, the following is obtained from Equation 3.

Substituting V _{acc found} in Equation 6 into Equation 7 yields:

That is, by observing t ₀ , t _n , and t _m , the acceleration voltage V _acc can be obtained using Equation 6 using L _t as a parameter. Further, L _c can be obtained by using Expression 8. Furthermore, L _t can be measured as a device parameter. For this reason, all parameters can be obtained by substituting L _t into the above equation.

When Expression 3 is modified with L _t as a constant, the following is obtained as a conversion basic expression of an arbitrary time t and mass M of the multi-turn time-of-flight mass spectrometer at the N turn.

Calibration of a time-of-flight mass spectrometer is synonymous with this time and mass conversion. Therefore, the above conversion equation can be obtained by measuring t ₀ , t _m , and t _n of the known mass M _ref .

Depending on the type of ion source, the received energy may change depending on the magnitude of the mass M _ref . However, Equation 9 holds near the mass M _ref , so the right term of Equation 9 can be treated as a conversion coefficient for various masses. For this reason, the linear form of mass and conversion coefficient is defined as follows using the function T of _Mref . Then, by fitting the function T and the actual measurement value, a conversion formula for the mass range in which the actual measurement value exists within a certain range can be obtained.

  Next, a method for eliminating ions other than ions having a predetermined mass-to-charge ratio will be described.

In a multi-turn time-of-flight mass spectrometer, particles with various masses orbit around a circular orbit, so that particles with a small mass may overtake particles with a large mass. In order to prevent this, a voltage for applying an unnecessary mass to the deflection electrode is turned on and off at an arbitrary timing and eliminated.

  FIG. 2 shows an example of voltage in a method in which two pulses are applied to the deflection electrode and transmitted between the pulses.

  This method uses a deflection electrode to exclude ions having a small mass-to-charge ratio and ions having a large mass-to-charge ratio in this order. In this method, first, the electric field of the deflection electrode is increased until the first ion included in the obtained mass-to-charge ratio range passes through the deflection electrode. As a result, ions having a mass to charge ratio smaller than the obtained mass to charge ratio range are excluded from the orbit. Next, the electric field of the deflection electrode is weakened until the last ion included in the obtained mass-to-charge ratio range passes through the deflection electrode. Then, ions having a desired mass-to-charge ratio remain in the orbit. Then, after the last ion included in the obtained mass-to-charge ratio range passes through the deflection electrode, the electric field of the deflection electrode is strengthened. Thereby, ions having a mass to charge ratio larger than the range of the mass to charge ratio are excluded from the orbit. However, the voltage of the deflection electrode is weakened before ions having a desired mass-to-charge ratio go around next time. Then, ions having a desired mass-to-charge ratio remain in the orbit and continue to circulate.

  FIG. 3 shows an example of voltage in a method of transmitting desired ions by applying one pulse or two pulses to the deflection electrode. In this method, one pulse is applied to the deflection electrode, and particles having a large mass in the first round are eliminated at the timing when the pulse is turned on. And the particle | grains with a small mass of the 2nd round are excluded until subsequent OFF timing.

  This method uses a deflection electrode to exclude ions having a large mass-to-charge ratio and ions having a small mass-to-charge ratio in this order. In this method, first, ions having a mass-to-charge ratio smaller than the obtained mass-to-charge ratio range pass through the deflection electrode. Thereafter, ions having a mass-to-charge ratio within the determined mass-to-charge ratio pass through the deflection electrode. When the last ion included in the obtained mass-to-charge ratio range has passed through the deflection electrode, the electric field of the deflection electrode is increased. Thereby, ions having a mass-to-charge ratio larger than the obtained mass-to-charge ratio range are excluded from the orbit.

  FIG. 4 is a diagram illustrating an example of a voltage when a particle having a small mass in the first round is excluded before the OFF timing of the incident electrode.

  In this method, the electric field of the incident electrode is strengthened until the first ion included in the obtained mass-to-charge ratio circles the orbit and reaches the incident position by the incident electrode. As a result, ions having a mass to charge ratio smaller than the obtained mass to charge ratio range are excluded from the orbit. The subsequent operation is the same as in the first method.

  FIG. 5 is a diagram illustrating an example of voltage when two pairs of deflection electrodes are used to remove particles having a small mass at the first electrode of the circular orbit and to remove particles having a large mass at the subsequent electrode.

  In either method, the deflection electrode is arranged on a circular orbit. The deflecting electrode is preferably arranged in the vicinity of the incident electrode as shown in FIG. Further, it is preferable to exclude the particles when they pass through the deflection electrode at the beginning of the round (first round) and when the particles that have passed through the deflection electrode next arrive at the deflection electrode (second round).

Method of calculating timing for overtaking If the position of the deflection electrode indicated by reference numeral 8 in FIG. 1 is L ₅ , the time required for the particle of mass M to pass therethrough is as follows from Equation 3.

Here the time passing through each of the deflection electrode for the greatest mass M _L smallest mass M _F of the mass range to be circulating and t _F, t _L, OFF the deflection electrodes from t _F to the time of t _L charged if ask transmitting particle mass M _F smaller mass particles and M _L is larger than the mass of the particle can be eliminated.

  The timing examples (1) and (2) in the case of the arrangement shown in FIG. 1 are shown below.

   An example of the mass range division measurement method will be described taking the multi-turn time-of-flight mass spectrometer of FIG. 1 as an example. FIG. 6 is a diagram showing each point of the multi-turn time-of-flight mass spectrometer of FIG.

FIG. 7 is a conceptual diagram illustrating the points P1 and P2. As shown in FIG. 7, a point on the orbit around the emission electrode and P1 and P2, the smallest mass M _F of the mass range of the flight distance in point P1 when N orbiting L _F, flight time was a t _F, the largest mass M _L is expressed as follows flight distance at point P2 when the N-1 orbiting L _L, the time-of-flight and t _L from equations 1 and 2.

Mass M _F at the same time is in the point P1 when the N orbiting, outrunning if the point P2 when the mass M _L is N-1 orbiting does not occur with here. Therefore, overtaking does not occur under the condition that the right side of Expression 12 is equal to the right side of Expression 13. Using this fact, the following equation can be obtained.

Note When point P1 and point P2 are in the same position, _{M F} is N orbiting, and just before _{the M L} overtakes at N-1 lap. Furthermore, when the required mass range M _{F to ML} does not satisfy Equation 14, the mass range can be divided. It becomes M _{1 =} sequentially substituting calculated from M _F and then expression 14 as follows: first & shy.

Finally it is possible to perform mass range dividing at a desired laps by repeating the calculation until the M _x ≧ M _L (segment). A calculation example is shown in the following table.

Since each segment can set L _F and L _L independently and can be calculated sequentially, for example, segments having different numbers of laps can be mixed. A calculation example is shown in the following table.

  If this calculation method is performed, the measurement range and the number of laps can be freely set. For example, the following measurement modes can be provided.

(1) Single measurement mode In this mode, the mass head and the number of laps (the mass tail is determined as a single unit), the mass center and the number of laps (the mass head and the mass tail are determined as a single unit), or the mass head and mass are determined. In this mode, the tail end (the maximum number of laps is determined as a single value) is specified, and measurement is performed with only one segment.
When the number N is specified, L _F and L _L are determined. When the mass head M ₁ is designated, M ₂ can be obtained from Equation 15. Similarly, M ₃ or later can also be determined. M _{1 to} M ₂ are the first segment, and so on. And mass spectrometry can be effectively performed by performing mass spectrometry for every segment. If the center of mass is determined, the segment can be obtained based on L _F and L _L as described in (3) below.

(2) Sequential number setting sequential division measurement mode This mode is a mode in which the mass-to-charge ratio range is sequentially divided by specifying the mass head, mass tail and the number of laps. The above table is an example of timing when the mass head = 10, the mass tail = 100, and the number of laps = 5 are designated. When the number of laps is specified, L _F and L _L are determined. Then, for example, if the head of mass is M ₁ and M _{2 and} later are obtained, it can be divided into segments sequentially. However, it is also possible to sequentially obtain the values before M _Z-1 with the mass tail as M _Z. In order to perform mass analysis with the most accuracy in a small range of mass-to-charge ratio, N should be maximized. In this case, the maximum number of revolutions N can be obtained based on Equation 14 using the mass head and mass tail.

(3) Number of laps individually set sequential division measurement mode This mode is a mode in which one or more masses are designated as one set of the mass start value, the mass tail, the base lap number, and the mass center value and the lap number. The mass range (mass center specification range) calculated from the specified center of mass value and the number of laps is measured at the specified lap. On the other hand, the top of mass, both ends of the center of mass specification range, and the end of the mass are sampled and connected at the base circumference. The above table shows an example of timing when mass start = 10, mass tail = 200, base round number = 1, mass center value = 28 (lap number = 50), mass center value = 32 (lap number = 30). It is. In this example, for example, consider the case where the mass center value = 28 (the number of laps = 50). L _F and L _L are determined from the number of laps N = 50. Let Ma and Mb be the minimum and maximum masses of the segment with the median value of 28. Then, Ma, Mb, the _{L F} and _{L L} of formula 14 relationship. Further, (Ma + Mb) / 2 = 28. By solving these two simultaneous equations, Ma and Mb can be obtained.

  In each of the above modes, the integrated number can be added as a parameter. Further, in the above (2) to (3), the segmental amplification factor in the next item can be added as a set value.

Amplification rate setting by segment Charged particles incident on the detector are signal-amplified by the detector, measured by a high-speed digitizer, and expressed by a voltage associated with the number of incident particles. Since overtaking originally occurs, mass range division is necessary to measure a wide range of masses. Further, there is no particle having any other mass in the divided mass range so as not to cause overtaking by the deflection electrode or the like. Therefore, it is not affected by saturation caused by a large signal in the vicinity, which is common in conventional time-of-flight mass spectrometers. In general, a high-speed digitizer uses the vicinity of the maximum signal intensity within the mass range as the maximum gain. However, since the minimum signal at this time is determined by the bit resolution of the AD converter, the dynamic range of the signal intensity depends on the high-speed digitizer. In a preferred embodiment of the present invention, the amplification factor of the detector or the high-speed digitizer can be set for each segment. Thereby, in the present invention, the dynamic range of the signal intensity can be made much larger than usual. The amplification factor is performed during the interval between each segment.

  FIG. 8 is a block diagram of a system in which a programmable gain amplifier is inserted between the detector and the AD converter. In FIG. 8, there is a programmable gain amplifier in the high-speed digitizer. However, in practice, if the gain can be set for each segment timing, the programmable gain amplifier may be installed outside the digitizer.

  FIG. 9 is a block diagram showing a system capable of setting the amplification factor of the detector in addition to the system of FIG. Note that the segment-specific gain may be set for either the measurement signal or the detector.

  The present invention relates to a time-of-flight mass spectrometer. Therefore, the present invention can be used in the field of physics and chemistry equipment.

  Further, according to the present invention, it is possible to provide a high-resolution mass spectrometer that is small, lightweight, and can be used generally. For this reason, this TOFMS can be brought into the field and a substance can be specified. As a result, the use of TOFMS is expected to spread to fields such as environment, pesticide analysis, drug detection, explosives detection, bedside medical care and the like, and the present invention can contribute to safety and security.

1 Ion source
2 Incoming electrode 3 Outgoing electrode 4, 5, 6, 7 Circulating electrode 9 Detector

Claims (11)

A mass spectrometry method using a multi-orbital time-of-flight mass spectrometer that measures the mass-to-charge ratio of ions using an orbit,
Obtain the flight time (t) after N laps, which is the flight time when the ions to be measured make N laps around the orbit,
The flight time (t _m , t _n ) after the lap which is the flight time in two or more laps of the first reference ion whose mass-to-charge ratio is already known, and the first reference ion The first calibration relating to the flight time before the lap which is the flight time when the aircraft flew only a distance that does not circulate, and the energy and the flight distance in the multi-round time-of-flight mass spectrometer obtained using (t ₀ ) Use constants,
A mass spectrometry method for measuring a mass-to-charge ratio of ions to be measured. Using the first calibration constant, a fitting function that is a function of the mass-to-charge ratio (M _ref ) of the first reference ion and the flight time (t) after the N laps is obtained,
Using a second reference ion having a known mass-to-charge ratio different from that of the first reference ion, a range of mass-to-charge ratios of ions that fit the fitting function is determined.
Exclude ions not included in the mass-to-charge ratio range from the measurement system,
The mass spectrometry method according to claim 1. The mass spectrometric method according to claim 2, comprising:
The multi-orbit time-of-flight mass spectrometer has a deflection electrode for excluding predetermined ions from the orbit,
A method for excluding ions that are not included in the mass-to-charge ratio range from the measurement system,
The electric field of the deflection electrode is strengthened until the first ion included in the determined mass to charge ratio range passes through the deflection electrode, thereby having a smaller mass to charge ratio than the determined mass to charge ratio range. Remove ions from the orbit,
Decreasing the electric field of the deflection electrode until the last ion in the determined mass to charge ratio range passes through the deflection electrode;
Thereafter, after the last ion included in the obtained mass-to-charge ratio range passes through the deflecting electrode, the electric field of the deflecting electrode is strengthened, thereby circulating the ions having a mass-to-charge ratio larger than the mass-to-charge ratio range. Exclude from orbit,
Mass spectrometry method. The mass spectrometric method according to claim 2, comprising:
The multi-orbit time-of-flight mass spectrometer has a deflection electrode for excluding predetermined ions from the orbit,
A method for excluding ions that are not included in the mass-to-charge ratio range from the measurement system,
After ions included in the determined mass-to-charge ratio range and ions having a mass-to-charge ratio smaller than the determined mass-to-charge ratio range pass through the deflection electrode, the electric field of the deflection electrode is strengthened. To eliminate ions having a mass-to-charge ratio larger than the determined mass-to-charge ratio from the orbit,
Further, the electric field of the deflection electrode is increased until the first ion included in the obtained mass-to-charge ratio range reaches the deflection electrode after completing the circulation, and thereby, the obtained mass-to-charge ratio of the obtained mass-to-charge ratio is finished. Exclude ions with mass-to-charge ratios less than the range from the orbit,
Mass spectrometry method. The mass spectrometric method according to claim 2, comprising:
The multi-round time-of-flight mass spectrometer has an incident electrode for introducing ions into the orbit, and a deflection electrode for excluding predetermined ions from the orbit,
A method for excluding ions that are not included in the mass-to-charge ratio range from the measurement system,
The electric field of the incident electrode is increased until the first ions included in the determined mass-to-charge ratio range around the orbit and reach the incident position by the incident electrode. Exclude ions with mass-to-charge ratios smaller than
Decreasing the electric field of the deflection electrode until the last ion in the determined mass to charge ratio range passes through the deflection electrode;
Thereafter, after the last ion included in the obtained mass-to-charge ratio range passes through the deflecting electrode, the electric field of the deflecting electrode is strengthened, thereby circulating the ions having a mass-to-charge ratio larger than the mass-to-charge ratio range. Exclude from orbit,
Mass spectrometry method. The mass spectrometric method according to claim 2, comprising:
The multi-round time-of-flight mass spectrometer includes a first deflection electrode for excluding ions having a mass to charge ratio smaller than the determined mass to charge ratio from the orbit, and the determined mass to charge ratio range. A second deflection electrode for excluding ions having a higher mass-to-charge ratio from the orbit,
This excludes ions with smaller and larger mass-to-charge ratios than the mass-to-charge ratio range from the orbit,
Mass spectrometry method. A flight when a first ion having a predetermined mass-to-charge ratio (M _F ) makes N orbits and flies to a certain point on the orbit is defined as L _F, and a mass-to-charge ratio different from the first ions ( When the second ion having M _L ) makes N-1 rounds and flies to a certain point on the round orbit, the flight is L _L.
Dividing the mass to charge ratio in the range of M _F to M _L such that M _F / M _L = (L _F / L _L ) ² ;
To measure the mass-to-charge ratio for each segment divided mass to charge ratio is in the range from M _L from M _F,
The mass spectrometry method according to claim 1. The segment is
Whether it is obtained sequentially using the mass head, which is the minimum mass-to-charge ratio subject to mass spectrometry, and a predetermined number of laps,
Whether it is obtained using the value of the center of mass of the segment ((M _F + M _L ) / 2) and a predetermined number of laps,
The maximum number of laps is calculated using the mass start, which is the minimum mass-to-charge ratio subject to mass analysis, and the mass tail, which is the maximum mass-to-charge ratio, subject to mass analysis. A segment with a value,
Is,
The mass spectrometry method according to claim 7. The segment is
The mass head, which is the minimum mass-to-charge ratio subject to mass analysis,
The mass tail, which is the maximum mass-to-charge ratio subject to mass analysis,
Specify the number of laps,
M _F / M _L = (L _F / L _L ) ² is a segment obtained sequentially based on the relationship of
The mass spectrometry method according to claim 7. The segment is
Including the first segment determined using the value of the center of mass of the segment ((M _F + M _L ) / 2) and the first number of laps,
Furthermore, the second segment obtained by using the mass head that is the minimum mass-to-charge ratio to be subjected to mass analysis, the second number of laps, and
A third segment determined using the mass tail, which is the maximum mass-to-charge ratio subject to mass spectrometry, and the third number of laps,
Is either a segment group containing either or both of
The mass spectrometry method according to claim 7. The multi-turn time-of-flight mass spectrometer has a detector and a digitizer,
Adjusting either or both of the amplification factor of the detector and the amplification factor of the digitizer for each segment;
The mass spectrometry method according to claim 7.

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