Time-of-flight mass spectrometer and ion extraction method

Abstract

One embodiment of the present invention is a TOFMS that ionizes a sample component by irradiating a sample with laser light, introduces generated ions into a flight space, causes the ions to fly, and subsequently detects the ions by a detector. The TOFMS comprises: an extraction electrode (3) that forms an extraction electric field for extracting ions from the sample; an acceleration electrode (4) that forms an acceleration electric field for accelerating the extracted ions; and a voltage control unit (10, 12) that applies a specific voltage to the extraction electrode after a specific delay time has elapsed from the time point when the sample is irradiated with the laser light. The potential distribution on the ion optical axis in the extraction electric field satisfies or substantially satisfies the solution of the following differential equation.　dϕ / dx = me\{1 / (dT / dv) – v / td\} In the formula, if ϕ is the potential, x is the position on the ion optical axis, me is the mass of the ion, td is the delay time, v is the velocity of the ion moved to a reference position x1 that is farthest from the sample at the time point when a delay time td has elapsed, and T is the time of flight from the position x1 to the detector position xD, dT / dv is obtained by the following expression when the potential at the position x1 is defined as ϕ1. 　dT / dv = ∫[x1, xD]v\{v2 + (2 / me)[ϕ1 - ϕ(x)\}-3 / 2dx

Description

Time-of-flight mass spectrometer and ion extraction method

[0001] The present invention relates to a time-of-flight mass spectrometer that uses laser desorption / ionization (LDI) including matrix-assisted laser desorption / ionization (MALDI), and to an ion extraction method for extracting generated ions from a sample and introducing them into a time-of-flight mass separator in the time-of-flight mass spectrometer.

[0002] Matrix-assisted laser desorption / ionization time-of-flight mass spectrometers (MALDI-TOFMS), which combine a MALDI ion source with a time-of-flight mass separator, generally have high mass resolution and mass accuracy, and are widely used for molecular weight measurement and structural analysis of biological compounds such as proteins.

[0003] As described in Non-Patent Document 1, in the MALDI method, ions with the same mass-to-charge ratio (m / z) generated by irradiating a sample with laser light have a relatively large variation in initial kinetic energy, which causes variation in the flight time of ions with the same m / z, i.e., a decrease in mass resolution. To solve this problem, an ion extraction technique called delayed extraction is widely used in MALDI-TOFMS.

[0004] As described in Non-Patent Document 1, in the delayed extraction method, for a predetermined time from the moment when the sample is irradiated with a short laser beam to generate ions, no substantial electric field is formed in the space near the sample surface, and the ions generated from the sample are allowed to move freely. Then, after the predetermined delay time has elapsed, a predetermined voltage is applied to the extraction electrode placed in front of the sample plate, and an extraction electric field is formed in the space between the sample plate and the extraction electrode, in which a potential gradient drops from the sample plate toward the extraction electrode.

[0005] After a certain delay time has elapsed, ions with relatively greater initial kinetic energy are located farther from the sample (i.e., closer to the extraction electrode). Therefore, ions with lower initial kinetic energy are accelerated by a larger potential than ions with higher initial kinetic energy due to the extraction electric field, and are introduced into the time-of-flight mass separator. This compensates for the difference in flight time between ions of the same m / z due to the difference in initial kinetic energy at the time of ion generation, thereby improving the time focusing of such ions.

[0006] "What is Pulsed Extraction (Delayed Extraction)?" [Online] [Retrieved August 26, 2024], Shimadzu Corporation, Internet <URL: https: / / www.shimadzu.co.jp / aboutus / ms_r / archive / files / MALDI-MS_TechRep / MALDI_TechRepV3.0_02.pdf>

[0007] As shown in Non-Patent Document 1, in a typical delayed extraction method, the potential gradient of the extraction field is linear. In this case, although it is relatively easy to determine the potential gradient (potential distribution), the range of initial velocities (range of initial kinetic energies) within which the time-of-flight can be accurately corrected is not very wide. Therefore, if the initial velocities of ions vary widely, it is not possible to fully correct the difference in the time-of-flight of ions of the same m / z, resulting in reduced mass resolution and mass accuracy in the mass spectrum. Alternatively, the range of initial velocities must be limited to achieve high mass accuracy and mass resolution, resulting in a reduced amount of ions and a reduced detection sensitivity.

[0008] The present invention has been made to solve these problems, and its main object is to provide a time-of-flight mass spectrometer and an ion extraction method that can accurately correct variations in flight time caused by large variations in the initial kinetic energies of ions with the same m / z when they are generated, thereby achieving high mass resolution and mass accuracy while improving detection sensitivity.

[0009] One aspect of the time-of-flight mass spectrometer according to the present invention is a time-of-flight mass spectrometer that ionizes components contained in a sample by irradiating the sample with a laser beam, and then introduces the generated ions into a flight space for flight and detects them with a detector, and comprises: an extraction electrode that is arranged between the sample and the flight space and forms an extraction field that extracts ions from the sample; an acceleration electrode that is arranged between the extraction electrode and the flight space and forms an acceleration field that accelerates the extracted ions; and a voltage control unit that does not form an extraction field at the time the laser beam is irradiated onto the sample, but applies a predetermined voltage to the extraction electrode to form an extraction field after a predetermined delay time has elapsed from the time of laser beam irradiation, and the potential distribution on the ion optical axis in the extraction field satisfies or substantially satisfies the solution of the following differential equation: dφ / dx=m e {1 / (dT / dv)-v / t d} where φ is the potential, x is the position on the ion optical axis (the position on the sample surface is set to x = 0), m e is the mass of the ion, t d is the delay time, v is the delay time t d is the velocity of the ion moving to the reference position x1, which is the furthest from the sample within a predetermined range on the ion optical axis at the time point when D The flight time of the ion is the time of flight of the ion from the point x1 to the point x2. dT / dv is calculated by the following equation when the potential at the point x1 is φ1: dT / dv = ∫[x1, x D ]v{v 2 + (2 / m e ) [φ1-φ(x)} -3 / 2 dx

[0010] Furthermore, one aspect of the ion extraction method according to the present invention is an ion extraction method in a time-of-flight mass spectrometer equipped with a laser light irradiation unit that irradiates a sample with laser light to ionize components contained in the sample, an extraction electrode that forms an extraction electric field that extracts generated ions from the sample, an acceleration electrode that forms an acceleration electric field that accelerates the extracted ions, a flight space in which the accelerated ions fly, and a detector that detects the ions after they have flown in the flight space, in which, in order to extract ions from the sample, an extraction electric field is not formed at the time of laser light irradiation on the sample, but a voltage is applied to the extraction electrode to form the extraction electric field after a predetermined delay time has elapsed from the time of laser light irradiation, and the potential distribution on the ion optical axis in the extraction electric field is determined to satisfy or substantially satisfy the solution of the following differential equation: dφ / dx=m e {1 / (dT / dv)-v / t d} where φ is the potential, x is the position on the ion optical axis (the position on the sample surface is set to x = 0), m e is the mass of the ion, t d is the delay time, v is the delay time t d is the velocity of the ion moving to the reference position x1, which is the furthest from the sample within a predetermined range on the ion optical axis at the time point when D The flight time of the ion is the time of flight of the ion from the point x1 to the point x2. dT / dv is calculated by the following equation when the potential at the point x1 is φ1: dT / dv = ∫[x1, x D ]v{v 2 + (2 / m e ) [φ1-φ(x)} -3 / 2 dx

[0011] The above-described aspects of the time-of-flight mass spectrometer and ion extraction method according to the present invention enable accurate correction of the time-of-flight of ions having the same m / z, i.e., the range of variation in the initial velocity (initial kinetic energy) of ions that allows high time focusing can be widened compared to conventional methods. This improves detection sensitivity while ensuring high mass resolution and mass accuracy in mass spectra, and can improve the accuracy of qualitative and quantitative analysis of components, for example, when using mass spectra to perform qualitative and quantitative analysis.

[0012] The present invention relates to a MALDI-TOFMS, an ion extraction field, and an ion extraction electric field.

[0013] [Supplementary explanation of the above embodiment] The ionization method used in the time-of-flight mass spectrometer (TOFMS) in the above embodiment may be any ionization method that ionizes components (compounds) in a sample by irradiating the sample with laser light. Therefore, it is not limited to MALDI, and a matrix-free laser desorption ionization (LDI) method, surface-assisted laser desorption ionization (SALDI) method, etc. may also be used.

[0014] Furthermore, although the TOFMS in the above embodiment is typically a linear TOFMS, the present invention is also applicable in principle to other types of TOFMS, such as a reflectron type. Furthermore, in a linear TOFMS, the flight space is generally a space without an electric field, but an ion lens for focusing ions may be provided in the flight space. The present invention is also applicable to TOFMS with such a configuration.

[0015] [Configuration and General Operation of a MALDI-TOFMS of One Embodiment] Figure 1 is a schematic diagram of a MALDI-TOFMS according to one embodiment of the present invention. For convenience of explanation, three mutually orthogonal axes, X, Y, and Z, are defined as shown in the figure. The TOFMS in this embodiment is a linear type.

[0016] As shown in FIG. 1 , a sample 20, the surface of which is coated with a MALDI matrix, is placed on a conductive sample plate 1 extending along the Y-Z plane. Between the sample 20 and a detector 7, an extraction electrode unit 3, an acceleration electrode unit 4, an ion lens unit 5, and a TOF unit 6 are arranged in this order along the X-axis. A plate voltage generator 11 is connected to the sample plate 1, an extraction voltage generator 12 to the extraction electrode unit 3, an acceleration voltage generator 13 to the acceleration electrode unit 4, and a lens voltage generator 14 to the ion lens unit 5, and predetermined voltages are applied to these units. The TOF unit 6 is connected to a reference potential such as ground potential. Each of the voltage generators 11, 12, 13, and 14 is controlled by a control unit 10, which is primarily composed of a computer (including a microcomputer).

[0017] The mass analysis operation in this MALDI-TOFMS will be briefly described. When a pulsed laser beam with a small diameter is irradiated onto the sample 20 from the laser beam irradiation unit 2, components (compounds) contained in the sample 20 are volatilized and ionized near the laser beam irradiation site. The generated ions are extracted from near the surface of the sample 20 generally in the X-axis direction (upward in FIG. 1 ) by the extraction electric field formed by the extraction electrode unit 3. The extracted ions are given a certain amount of kinetic energy by the acceleration electric field formed by the acceleration electrode unit 4, and are accelerated in the X-axis direction.

[0018] The accelerated ions are converged by the converging electric field formed by the ion lens unit 5 so that their spread in the Y-Z plane converges on the ion optical axis 21, and are then introduced into the flight space formed by the TOF unit 6. The flight space is a field-free space, and ions fly through it at a substantially constant speed corresponding to the m / z of each ion. Because the larger the m / z of an ion, the slower its flight speed. Therefore, various ions generated in the sample 20 at substantially the same time reach the detector 7 faster (i.e., with a shorter flight time) the smaller their m / z. Therefore, each ion is spatially and temporally separated in the X-axis direction according to its m / z. The detector 7 constantly outputs an intensity signal corresponding to the amount of incident ions. Since the flight time of each ion corresponds to its m / z, as described above, a mass spectrum showing the relationship between the m / z of the ions and their signal intensity can be created based on the intensity signal.

[0019] [Delayed Extraction Method in the Present Embodiment] Generally, the initial kinetic energy given to ions generated from the sample 20 by laser light irradiation varies considerably, and this variation causes variation in the flight time of ions of the same m / z. As described above, in order to reduce the effect of this variation in initial kinetic energy, a typical MALDI-TOFMS employs an ion extraction method called delayed extraction.

[0020] In the delayed extraction method, as described in Non-Patent Document 1, an extraction electric field is not formed during laser light irradiation. Specifically, the potential gradient on the ion optical axis 21 between the extraction electrode 3 and the sample plate 1 is kept flat. As a result, individual ions generated from the sample 20 move at a velocity corresponding to their initial kinetic energy. Therefore, after a predetermined delay time has elapsed from the time of laser light irradiation, ions with greater initial kinetic energy are located farther from the sample 20, i.e., closer to the extraction electrode 3. Therefore, after this delay time has elapsed, an extraction electric field is formed to form a potential gradient that slopes downward from the sample 20 toward the extraction electrode 3. As a result, ions located relatively closer to the sample 20 on the ion optical axis 21 (i.e., ions with smaller initial kinetic energy) are imparted with greater kinetic energy than ions located farther from the sample 20. That is, even for ions with the same m / z, ions located relatively closer to the sample 20 on the ion optical axis 21 are introduced into the TOF unit 6 at a greater velocity than ions located farther from the sample 20. This makes it possible to correct the difference in flight time due to the difference in initial kinetic energy, and to reduce the influence of variations in flight time of ions of the same m / z.

[0021] However, as already mentioned, conventional delayed extraction methods have the problem that the range of variation in initial velocity (initial kinetic energy) that can be corrected with sufficiently high accuracy is narrow because the potential gradient of the extraction field is linear. In contrast, in the MALDI-TOFMS of this embodiment, the potential gradient of the extraction field is nonlinear, thereby expanding the range of variation in initial velocity that can be corrected with high accuracy, and increasing the number of ions that can be reflected in one peak on the mass spectrum, thereby improving detection sensitivity. Next, we will explain how to determine the potential distribution in the extraction field.

[0022] 2 and 3 are explanatory diagrams for explaining how to determine the potential distribution on the ion optical axis 21 of the extraction electric field. In FIG. 2, the horizontal axis represents the position (distance) x on the ion optical axis 21 when the surface of the sample 20 is set to x=0, and the vertical axis represents the potential φ. In the diagram, x1 represents the distance from the laser beam irradiation point that the ion (hereinafter referred to as the "first ion") with the fastest initial velocity (velocity: v1) moves at a predetermined delay time x d The position x2 at which the first ion is present after the same delay time t d Therefore, x1 = v1t d , x2 = v2t d , and x D is the position of the detector 7.

[0023] Furthermore, let φ = φ(x) be the appropriate potential at position x, and φ = φ(x) be the appropriate potential at position x. Let v be the velocity at which an ion with velocity v moves to position x. 21 , the time it takes for the ion to travel to position x1 is Δt 21 In addition, let v be the velocity when the ion reaches (passes) position x1 after the extraction electric field is formed (i.e., after acceleration starts), and let v be the velocity of the ion when it reaches (passes) position x1. D Let T(v) be the flight time between these two ions. Furthermore, let us define Δx: = x1 - x2, Δv: = v1 - v2, and Δφ: = φ1 - φ2. Note that the "ion with the fastest initial velocity" mentioned here simply means the fastest ion within the assumed range, and does not mean that there are no ions with a faster initial velocity among the ions generated. The reason for this will be explained later.

[0024] To briefly explain how to determine the potential distribution, first, as shown in FIG. 3, attention is paid to the first ion having the fastest initial velocity, and the delay time t d The position x1 and detector x at the time when D As shown in FIG. 2, if the position x1 is the boundary between the extraction region and the acceleration region, the potential distribution between the position x1 and the detector xD The potential distribution between the position x1 and the detector x2 is determined by the voltages applied to the accelerating electrode section 4, the ion lens section 5, and the TOF section 6, and is therefore determined at the time of designing the device. D The potential distribution between the electrodes is known. Although an example of this potential distribution is shown in FIG. 2, the shape of the potential distribution is not limited to this.

[0025] Next, as shown in FIG. 3, attention is focused on a second ion whose initial velocity is slightly slower than that of the ion with the fastest initial velocity, and the distance between positions x1 and x2 is calculated. D By using the potential distribution between the positions x1 and x2, and imposing a condition that the difference between the flight time of the second ion and the flight time T(v) of the first ion becomes zero, the potential gradient in the minute region Δx near the second ion, specifically between the positions x1 and x2, is determined. D The potential distribution between the ions is determined. The ions with the initial velocity that is smaller by a small value are then generated. d At this point, we focus on the ion that is closer to x = 0 and determine the potential gradient in the vicinity of that ion. This process is repeated, and the potential gradient in the vicinity of all ions with the same m / z and initial velocity can be determined.

[0026] In order to obtain an equation that represents the potential distribution between 0 and x1 obtained by following the above procedure, the law of conservation of energy, the equation of motion, and the equation that represents isochronism are used. Regarding the relationship between the first ion and the second ion described above, the law of conservation of energy can be used to obtain the following equation (1): (1 / 2)m e v2 2 +φ2 = (1 / 2) m e v 21 2 +φ1 ... (1) where m e is the mass of the ion in question. Using the equation of motion, we can obtain the following equation (2): m e (dv / dt)=-(dφ / dx) (2) Furthermore, from the isochronous condition that the first ions and the second ions arrive at the detector 7 at the same time, the following equation (3) can be obtained. 21 +T(v21 ) = T(v1) ... (3)

[0027] First, transform equation (1) to the following equation (4): 21 =√{v2 2 -(2Δφ / m e ) v 21 -v2 ≒ -Δφ / (m e v2) ...(4) By rewriting equation (4) using Δv, equation (5) is obtained. v1-v 21 = -Δv + Δφ / (m e v2) …(5)

[0028] On the other hand, the following equation (6) can be obtained from equation (2): Δt 21 = {m e Δx(v2-v 21 )} / dφ (6) From equation (6) and equation (3) showing isochronism, the following equation (7) is obtained. e Δx(v2-v 21 )} / dφ=T(v1)−T(v 21 ) …(7)

[0029] From equations (4), (5), and (7), the following equation (8) can be obtained: Δx / v={Δv+Δφ / (m e v)}dT(v) / dv ... (8) From equation (8), the following equation (9) is obtained: dφ / dx = m e {1 / (dT / dv)-v / t d} ...(9) This equation (9) expresses the relationship between a small distance and a small potential, and is therefore a differential equation that determines the potential distribution in the extraction electric field.

[0030] This differential equation contains a differential component dT / dv, which can be calculated as follows. The flight time T of an ion with a velocity v can be obtained by the following integral formula: T(v) = ∫[x1, x D ]dx / v(x, v) ... (11) By rewriting equation (11) in the form of partial differential, equation (12) is obtained. dT(v) / dv = ∫[x1, x D ][∂{1 / v(x,v)} / ∂v]dx ∂{1 / v(x,v)} / ∂v]=-{1 / v(x,v)2}{∂v(x,v) / ∂v} …(12)

[0031] On the other hand, equation (2) based on the law of conservation of energy can be rewritten as the following equations (13) and (14): v(x, v) = √{v 2 + (2 / m e ) [φ1 - φ(x)] ... (13) ∂(x, v) / ∂v = v / v(x, v) ... (14) Using equations (12), (13), and (14), equation (15) is obtained. dT(v) / dv = ∫[x1, x D ]v{v 2 + (2 / m e ) [φ1-φ(x)} -3 / 2 dx...(15)

[0032] Thus, the differential equation that determines the potential distribution in the extraction electric field is equation (9) shown below, and dT / dv in this equation (9) can be calculated using equation (15) above. e {1 / (dT / dv)-v / t d ...(9) Mass of ion m e If it is possible to analytically solve this differential equation by applying the above conditions, it is possible to obtain the potential distribution (potential gradient) in the range of x from 0 to x1.

[0033] [Specific Design Method for Potential Distribution in Extraction Field] The potential distribution in an ideal or near-ideal extraction field can be achieved by following the above conditions, but applying it to a device requires a solution to the differential equation. However, it is practically impossible to analytically solve the differential equation shown in equation (9) to obtain a general solution. Therefore, it is sufficient to numerically solve the differential equation using a commonly known method.

[0034] Specifically, as shown in FIG. 2, when the position x1 is set at the boundary between the extraction electric field and the acceleration electric field, x1 to x D In other words, the potential distribution φ(x) on the ion optical axis in the acceleration region, the convergence region, and the flight region can be determined in advance. For example, x1 to x DIf the potential distribution φ(x) in the range of e Then, we can calculate the flight time T(v) of the ion with mass m e , delay time t d Using the parameter, dT / dv is found using equation (15), and the differential equation in equation (9) is solved using a numerical method such as the Runge-Kutta method to find the potential distribution φ in the infinitesimal range Δx between positions x1 and x2. Of course, other numerical methods for solving differential equations may also be used.

[0035] As a result, the ion position is expanded to the sample 20 side by the range of positions x1 to x2, i.e., x2 to x D The potential distribution in the range of x is determined. This potential distribution is then used to calculate the time of flight of the ion departing from position x2, and dT / dv is found using equation (15). The differential equation in equation (9) is then solved using a numerical method such as the Runge-Kutta method to determine the potential distribution φ in a small range on the sample 20 side of position x2. This calculation is repeated. In this way, the potential distribution in the entire range on the sample 20 side of position x1 can be determined.

[0036] As is clear from the above calculation method, if the delay time t d At the time when time has passed, positions x1 to x D If there are ions that have already reached the range, they are not included in the above calculation. In other words, for such ions, the energy is not focused by the extraction electric field, and the variation in flight time is not corrected. In this method, there is an upper limit (vt) for the initial velocity (v) that achieves ideal energy focusing. d However, since there is usually an upper limit to the initial velocity of ions generated by the MALDI method, there is no practical problem if the maximum value is determined with a sufficient margin, for example, 1.5 to 2 times the upper limit.

[0037] [Application to the Apparatus] As described above, the potential distribution on the ion optical axis 21 in the extraction electric field can be determined, and therefore, in the MALDI-TOFMS of this embodiment, the configuration of the extraction electrode unit 3 and / or the voltage generated by the extraction voltage generator 12 can be determined so as to realize the determined potential distribution. However, since it is difficult to precisely reproduce the nonlinear potential gradient determined as described above, the potential gradient can be approximately reproduced.

[0038] As one example, the extraction electrode unit 3 may be configured to include a number of thin plate electrodes aligned along the ion optical axis 21, with different voltages applied to each thin plate electrode. However, in a MALDI-TOFMS, the distance between the surface of the sample 20 and the acceleration electrode unit 4 is generally quite short, making it difficult to arrange a number of thin plate electrodes aligned along the ion optical axis 21 in the space between them. Therefore, the extraction electrode unit 3 may be configured to be approximately cylindrical with the ion optical axis 21 as its axis, and the cross-sectional shape of its inner circumferential surface in a plane including the ion optical axis 21 may be curved, so that the potential gradient formed on the ion optical axis 21 becomes nonlinear or approximately nonlinear as described above. Alternatively, the extraction electrode unit 3 may be configured as a substantially cylindrical resistor with the ion optical axis 21 as its axis, and the thickness of the resistor may be varied along the ion optical axis 21, so that the potential gradient formed on the ion optical axis 21 becomes nonlinear or approximately nonlinear as described above.

[0039] The above embodiment is merely an example of the present invention, and it goes without saying that any appropriate modifications, alterations, or additions made within the spirit of the present invention will also fall within the scope of the claims of the present application.

[0040] Aspects It will be apparent to those skilled in the art that the exemplary embodiments described above are examples of the following aspects.

[0041] (Item 1) One aspect of the time-of-flight mass spectrometer according to the present invention is a time-of-flight mass spectrometer that ionizes components contained in a sample by irradiating the sample with a laser beam, and then introduces the generated ions into a flight space for flight and detects them with a detector, and comprises: an extraction electrode that is arranged between the sample and the flight space and forms an extraction field that extracts ions from the sample; an acceleration electrode that is arranged between the extraction electrode and the flight space and forms an acceleration field that accelerates the extracted ions; and a voltage control unit that does not form an extraction field at the time the laser beam is irradiated onto the sample, but applies a predetermined voltage to the extraction electrode to form an extraction field after a predetermined delay time has elapsed from the time of laser beam irradiation, and the potential distribution on the ion optical axis in the extraction field satisfies or substantially satisfies the solution of the following differential equation: dφ / dx=m e {1 / (dT / dv)-v / t d} where φ is the potential, x is the position on the ion optical axis (the position on the sample surface is set to x = 0), m e is the mass of the ion, t d is the delay time, v is the delay time t d is the velocity of the ion moving to the reference position x1, which is the furthest from the sample within a predetermined range on the ion optical axis at the time point when D The flight time of the ion is the time of flight of the ion from the point x1 to the point x2. dT / dv is calculated by the following equation when the potential at the point x1 is φ1: dT / dv = ∫[x1, x D ]v{v 2 + (2 / m e ) [φ1-φ(x)} -3 / 2 dx

[0042] (Item 4) One aspect of the ion extraction method according to the present invention is an ion extraction method in a time-of-flight mass spectrometer equipped with a laser light irradiation unit that irradiates a sample with laser light to ionize components contained in the sample, an extraction electrode that forms an extraction electric field that extracts generated ions from the sample, an acceleration electrode that forms an acceleration electric field that accelerates the extracted ions, a flight space in which the accelerated ions fly, and a detector that detects the ions after flying in the flight space, in which, in order to extract ions from the sample, an extraction electric field is not formed at the time of laser light irradiation on the sample, but a voltage is applied to the extraction electrode to form the extraction electric field after a predetermined delay time has elapsed from the time of laser light irradiation, and the potential distribution on the ion optical axis in the extraction electric field is determined to satisfy or substantially satisfy the solution of the following differential equation: dφ / dx=m e {1 / (dT / dv)-v / t d} where φ is the potential, x is the position on the ion optical axis (the position on the sample surface is set to x = 0), m e is the mass of the ion, t d is the delay time, v is the delay time t d is the velocity of the ion moving to the reference position x1, which is the furthest from the sample within a predetermined range on the ion optical axis at the time point when D The flight time of the ion is the time of flight of the ion from the point x1 to the point x2. dT / dv is calculated by the following equation when the potential at the point x1 is φ1: dT / dv = ∫[x1, x D ]v{v 2 + (2 / m e ) [φ1-φ(x)} -3 / 2 dx

[0043] The time-of-flight mass spectrometer described in paragraph 1 and the ion extraction method described in paragraph 4 can accurately correct the time of flight of ions having the same m / z, that is, the range of variation in the initial velocity (initial kinetic energy) of ions that can achieve high time focusing can be wider than ever before. This makes it possible to improve detection sensitivity while ensuring high mass resolution and mass accuracy in mass spectra, and can improve the accuracy of qualitative and quantitative analysis of components, for example, when using mass spectra to perform qualitative and quantitative analysis.

[0044] (Items 2 and 5) In the time-of-flight mass spectrometer described in item 1 or the ion extraction method described in item 4, the reference position can be a position corresponding to the boundary between an extraction region where the extraction electric field mainly acts and an acceleration region where the acceleration electric field mainly acts.

[0045] In the time-of-flight mass spectrometer described in item 2 and the ion extraction method described in item 5, the reference position x and the detector position x d The electric field in the region through which the ions pass (fly) between x and x can be determined in advance. This makes it easy to calculate the flight time of the ions departing from the reference position x to reach the detector after the delay time has elapsed, and makes it easy to solve the differential equation by numerical solution.

[0046] (Items 3 and 6) In the time-of-flight mass spectrometer according to item 1 or 2 or the ion extraction method according to item 4 or 5, the potential distribution on the ion optical axis in the extraction electric field is determined by the distance from the reference position x1 to the detector position x2. D The potential distribution between position x1 and position x2, which is a small distance closer to the sample than position x1, can be determined by repeating the following calculations: calculating the flight time of an ion having an assumed mass, with flight velocity as a variable, using the known potential distribution between x1 and x2; and solving the differential equation by a numerical method based on the result.

[0047] The time-of-flight mass spectrometer described in paragraph 3 and the ion extraction method described in paragraph 6 can reliably solve differential equations that are difficult to solve analytically, and determine the potential distribution in the extraction electric field.

[0048] REFERENCE SIGNS LIST 1... Sample plate 2... Laser light irradiation section 3... Extraction electrode section 4... Acceleration electrode section 5... Ion lens section 6... TOF section 7... Detector 10... Control section 11... Plate voltage generation section 12... Extraction voltage generation section 13... Acceleration voltage generation section 14... Lens voltage generation section 20... Sample

Claims

1. A time-of-flight mass spectrometer that ionizes components contained in a sample by irradiating the sample with a laser beam, introduces the generated ions into a flight space, and detects them with a detector, comprising: an extraction electrode that is positioned between the sample and the flight space and forms an extraction field that extracts ions from the sample, an acceleration electrode that is positioned between the extraction electrode and the flight space and forms an acceleration field that accelerates the extracted ions, and a voltage control unit that does not form an extraction field at the time the laser beam is irradiated onto the sample, but applies a predetermined voltage to the extraction electrode to form an extraction field after a predetermined delay time has elapsed from the time of laser beam irradiation, and the potential distribution on the ion optical axis in the extraction field satisfies or substantially satisfies the solution of the following differential equation: dφ / dx=m e {1 / (dT / dv)-v / t d } where φ is the potential, x is the position on the ion optical axis (the position on the sample surface is set to x = 0), m e is the mass of the ion, t d is the delay time, v is the delay time t d is the velocity of the ion moving to the reference position x1, which is the furthest from the sample within a predetermined range on the ion optical axis at the time point when D The flight time of the ion is the time of flight of the ion from the point x1 to the point x2. dT / dv is calculated by the following equation when the potential at the point x1 is φ1: dT / dv = ∫[x1, x D ]v{v 2 + (2 / m e ) [φ1-φ(x)} -3 / 2 dx 2. A time-of-flight mass spectrometer according to claim 1, wherein the reference position is a position corresponding to the boundary between an extraction region where the extraction electric field mainly acts and an acceleration region where the acceleration electric field mainly acts.

3. The potential distribution on the ion optical axis in the extraction electric field is determined by the distance from the reference position x1 to the detector position x D 2. The time-of-flight mass spectrometer according to claim 1, wherein the potential distribution between position x1 and position x2 is determined by repeating the following calculations: calculating the time of flight of an ion having an assumed mass using a known potential distribution between position x1 and position x2, with the flight velocity as a variable, and solving the differential equation by a numerical method based on the result to determine the potential distribution between position x1 and position x2 which is a small distance closer to the sample than position x1.

4. In a time-of-flight mass spectrometer equipped with a laser beam irradiation unit that irradiates a sample with laser beam to ionize components contained in the sample, an extraction electrode that forms an extraction electric field that extracts the generated ions from the sample, an acceleration electrode that forms an acceleration electric field that accelerates the extracted ions, a flight space in which the accelerated ions fly, and a detector that detects the ions after they have flown in the flight space, an ion extraction method that performs delayed extraction by not forming an extraction electric field at the time of laser beam irradiation on the sample but applying a voltage to the extraction electrode to form an extraction electric field after a predetermined delay time has elapsed from the time of laser beam irradiation to extract ions from the sample, wherein the potential distribution on the ion optical axis in the extraction electric field is determined to satisfy or substantially satisfy the solution of the following differential equation: dφ / dx=m e {1 / (dT / dv)-v / t d } where φ is the potential, x is the position on the ion optical axis (the position on the sample surface is set to x = 0), m e is the mass of the ion, t d is the delay time, v is the delay time t d is the velocity of the ion moving to the reference position x1, which is the furthest from the sample within a predetermined range on the ion optical axis at the time point when D The flight time of the ion is the time of flight of the ion from the point x1 to the point x2. dT / dv is calculated by the following equation when the potential at the point x1 is φ1: dT / dv = ∫[x1, x D ]v{v 2 + (2 / m e ) [φ1-φ(x)} -3 / 2 dx 5. The ion extraction method according to claim 4, wherein the reference position is a position corresponding to the boundary between an extraction region where the extraction electric field mainly acts and an acceleration region where the acceleration electric field mainly acts.

6. The potential distribution on the ion optical axis in the extraction electric field is determined by the distance from the reference position x1 to the detector position x D 5. The ion extraction method according to claim 4, wherein the potential distribution is determined by repeating the following calculations: calculating a time of flight of an ion having an assumed mass, with the flight velocity as a variable, using a known potential distribution between position x1 and position x2 of the sample; and solving the differential equation by a numerical method based on the result of the calculation to determine the potential distribution between position x1 and position x2 that is a small distance closer to position x1.

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