JP2001283768A - Time of flight type mass spectrometer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain high resolution TOFMS spectrum stably on a steady basis by incorporating a post acceleration type ion detector. SOLUTION: In a time of flight type mass spectrometer wherein an ion is flown from an ion reservoir with the multistage acceleration field and re- accelerated for detecting near the ion detector, the voltage in each acceleration field meeting secondary convergence condition corresponding to re-acceleration voltage is to be set so as to obtain resolution equivalent to that in the case of non re-acceleration.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a high-performance time-of-flight mass spectrometer incorporating a reflector type spectroscopic section having a multi-stage acceleration section and a post-accelerator type ion detector.

[0002]

2. Description of the Related Art With the rapid development of high-speed electronic circuit technology and vacuum technology in recent years, a time-of-flight mass spectrometer (TOFMS) has been developed.
However, high-resolution spectra exceeding 10,000 have been obtained, and mass spectrometry of 10,000 to 100,000 by ESI or MALDI, which is a soft ionization method for a trace amount of biopolymers, has been performed. The demand for high-sensitivity, high-resolution TOFMS as an apparatus has been increasing year by year. In order to stably obtain a high-resolution mass spectrum, it is essential to design an excellent spectrometer. As is well known, in order to obtain a high-resolution mass spectrum even with an ion beam having a spatial spread (δ) in the TOFMS flight direction, a two-stage acceleration method is employed in the ion acceleration unit. By employing the two-stage acceleration method, a first-order spatial convergence condition is satisfied. Further, by using a mirror reflection type reflector in the spectroscopic part of the two-stage acceleration method and the TOFMS and optimizing each parameter of the ion optical meter, it is possible to design a spectrometer that satisfies a perfect quadratic convergence condition regarding δ. .

[0003] The reflector section has a one-stage and a two-stage type. When the two-stage reflector section is employed, two metal meshes (or grids) having an ion transmittance of about 80%, which is frequently used by flying ions, are used. You have to make a total of four round trips. Therefore, only the reflector section (1-0.
8 ⁴ ) × 100 = 59%, a little less than 60% of ion loss occurs. On the other hand, the one-stage reflector type has one mesh,
The Ionrosu reflector portion (1-0.8 ²⁾ × 100
= 36%, which is more advantageous than the two-stage type from the viewpoint of ion transmittance.

At present, four types of mass spectrometers are commercially available. One of the outstanding features of TOFMS over a magnetic field type MS, a quadrupole type MS, and a cyclotron resonance type MS is that an ion (M = 1) (z = 1)
It has the characteristic that the mass range of ions that can be measured even with / z) is wide (in principle, the mass range is infinite).

In particular, in MALDI / TOFMS, biomolecules having a mass number M of tens of thousands to hundreds of thousands can be easily ionized and mass spectrometry can be easily performed, which is indispensable for primary structure analysis of small proteins. Established as a device. As such a TOFMS ion detector, an electron multiplier (EM tube) as a secondary electron multiplier or a microchannel plate (MCP) is used.

However, in order to efficiently detect high-mass ions exceeding 10,000 using an ion detector of an EM tube or MCP and convert them to ion-electrons and measure them with an appropriate sensitivity, flying comes. It is necessary to implant ions at the ion detector surface at a flight speed of 10 ⁴ m / s or more. For example, when the velocity v ₀ of the monovalent (z = 1) ion M / s of the mass M is accelerated by the ion acceleration voltage U ₀ , the equation (1) v ₀ = 1.4 × 10 ⁴ (U ₀ / M) ^1/2 (1) (U ₀ : Volt, M: Dalton), and v ₀ decreases as the mass M increases. From equation (1), for example, ions of M / z ≒ 10,000 have U ₀ ≧ 5000 volts, and ions of M / z ≒ 100,000 have U ₀ ≧ 50,
It is desirable to accelerate at 000 volts (50 kV).

However, keeping the ion accelerating section at an extremely high potential of 50 kV is not always advantageous in terms of practical apparatus design. That is, a sample introduction unit is naturally attached to the ion accelerating unit, and the cost for discharging measures of each component including these components is increased. In particular, in a general-purpose device, it is desired that the voltage of the ion acceleration unit be as low as possible. At the expense of keeping the ion detector of the ion detector at a high potential opposite to the polarity of the ion,
A method of re-accelerating the velocity of the ions once accelerated by the ion accelerating unit at a relatively low voltage in the vicinity of the ion detector (post-acceleration method) is already known, and a magnetic field type or quadrupole type MS has already been known. Are often used as high-sensitivity ion detectors and high-mass ion detectors, and are sometimes called post-accelerator detectors or simply high-sensitivity ion detectors.

[0008]

Although a secondary ion optical meter considering a post-accelerator detector has been proposed, a TOFMS apparatus has not been proposed yet from a practical viewpoint. That is, the higher the post-accelerator voltage Ud for re-acceleration near the ion detector, the higher the mass of ions can be measured with higher sensitivity. is there. In particular, when a discharge occurs in the ion detector, an expensive ion detector or a subsequent high-speed electric circuit is destroyed.

Further, when a liquid chromatograph, which has been particularly noticed in recent years, and a TOFMS are combined, a vertical acceleration TOFMS is used as the TOF. In this case, in particular, the two-stage accelerator region where a large amount of neutral molecules and ions derived from the sample and the mobile phase solvent directly fly from the external ion source, as well as the spectroscopic unit and ion detection unit that want to maintain a high vacuum at all times. The degree of vacuum also decreases. For this reason, it is desirable that the post-accelerator voltage of the ion detection unit can be increased or decreased according to the mass of the sample to be analyzed, the degree of vacuum that can be maintained, and the degree of contamination around the mass. In particular, an excessive post-accelerator voltage is not necessary for the mass of the sample ions to be analyzed, and it is desirable to have a function capable of easily selecting an appropriate post-accelerator voltage according to the analysis target. However, simply changing the post-accelerator voltage inevitably lowers the resolution due to restrictions on ion optics (secondary convergence conditions are broken).

An object of the present invention is to solve the above-mentioned problems, and an object of the present invention is to incorporate a post-accelerator type ion detector so that a high-resolution TOFMS spectrum can be constantly and stably obtained.

[0011]

SUMMARY OF THE INVENTION The present invention is a time-of-flight mass spectrometer that flies ions from an ion reservoir by a multi-stage acceleration field and detects the ions by re-acceleration near an ion detector.
The voltage of each acceleration field that satisfies the secondary convergence condition is set according to the re-acceleration voltage, so that the same resolution as in the case where no re-acceleration is performed is obtained.

[0012]

Embodiments of the present invention will be described below with reference to the drawings.

FIG. 1 is a diagram showing a basic configuration of a time-of-flight mass spectrometer of the present invention, and FIG. 2 is a basic configuration diagram showing a voltage and a power supply supplied to each section when ions to be analyzed are positive. In FIG. 1, an ion beam generated by an external ion source 1 such as EI, CI, FAB, ESI, or APCI is introduced into an ion reservoir 2 by flying an accelerated ion beam in the X direction, or ions generated by MALDI. Exists in the ion reservoir 2. This ion reservoir 2 includes a push-out plate 3 and a grid G1. When drifting the ion beam from the external ion source 1 into the ion reservoir 2, the push-out plate and the grid G1 are kept at the same potential. Ion reservoir 2 and TOF maintained in high vacuum
The optical axis (Y direction) of the MS spectral unit 6 is orthogonal to the optical axis. Therefore, when traveling ions through the TOFMS spectroscopic unit,
After the drift traveling ion beam fills the ion reservoir 2 for a certain period of time, a voltage having the same polarity as that of the ions is applied to the push-out plate 3 to give a potential difference U1 to the grid G1. At the same time, grid G1 (4) and grid G
The TOFMS spectroscopy unit 6 is caused to fly by giving a potential difference U2 between 2 (5) and the reflector unit 9 is passed through the grid G3 (7).
After reflection by 180 degrees, the ion signal is detected by the ion detector 11 and mass analysis is performed after passing through the grid G5 (10). The grid G4 (8) has a function of discarding ions having excessive kinetic energy to the outside in the reflector portion, but is not indispensable in the present invention.

When the charge of the ion to be analyzed is positive, the voltage and power supply supplied to each section are as shown in FIG. That is, the grid G2 (5) and the grid G3 (7) are set to the ground potential, the voltage of the push-out plate 3 is U1, the voltage of the grid G1 (4) is U2, and the voltage of the ion detector 11 is U5. The voltage of grid G4 (8) is changed to U4
And If the polarity of the ion to be analyzed is negative,
U5 all have voltages of the opposite polarity to FIG. Gap d ₁ of one step accelerating portion, the gap d ₂ of the two-stage acceleration field, grid G2
(5) the grid G3 (7) Distance d _3/2 (drift space distance d ₃₎ between a reflector length d _4.

SW1 is a push-out plate 3
When the switch SW1 supplies U1, the ions are accelerated and discharged in the direction of the TOFMS spectroscopy unit 6. Monovalent ion of mass M Dalton (M ⁺ )
Is given acceleration energy eU ₀ according to equation (1),
After passing through the grid G5 (10) at the speed of v ₀ , post-acceleration is performed. Assuming that the final speed on the ion detector 11 is v _d , v _d is given by equation (2).

V _d = 1.4 × 10 ⁴ (| U ₀ −U ₅ |) ^1/2 / M (m / s) (2) (U ₀ , U ₅ : bolt, M: Dalton) U ₀ When fixed, the varying along the voltage U ₅ of opposite polarity to the user's desired conditions.

Next, setting of each parameter for satisfying the secondary convergence condition at the time of post-acceleration will be described. A TO that satisfies the secondary convergence condition that is uniquely determined in each case when the post-accelerator is considered and when it is not considered.
The ion optical parameters of FMS are necessarily different. Also, when the post-accelerator voltage is changed linearly,
A study will be made on how the ion optical parameter that uniquely determines the secondary convergence condition changes. Set each parameter as follows. Total flight time: T = T (k) Central ion acceleration voltage: U ₀ Single-stage acceleration unit voltage: U ₁ = αU ₀ , single-stage acceleration field gap: d ₁ Double-stage acceleration unit voltage: U ₁ = βU ₀ , 2 Step acceleration field gap: d ₂ Coefficient of the center position of the ion beam in the single step acceleration field: f (0 <f <1) U ₀ = (fα + β) U ₀ , that is, fα + β = 1, fα = α1, and α1 + β = 1 Spread coefficient from the beam center position in the single-stage acceleration field: k = (1 + δ) Spread of the ion beam position in the single-stage acceleration field: δ × f × d ₁ Drift space distance: d ₃ Drift space flight velocity of the center beam: v ₀ ( Final velocity of ions at k = 1) Reflector voltage: U ₄ = ρU ₀ , Reflector length: d ₄ Post-accelerator voltage: U _d = U ₅ = γU ₀ (γ is given as a re-acceleration coefficient) Post-accelerator space : d ₅ is calculated from these parameters That total flight time T from the ion exit point to the ion detector in consideration of the post-accelerator is given by equation (3).

[0018]

(Equation 1) In Equation (3), the first term in parentheses is the flight distance in the single-stage acceleration field, the second term is the net flight distance in the two-stage acceleration field,
The term is the flight distance in free space, the fourth term is the flight distance in the reflector section, the fifth term is the flight distance in the post-accelerator section,
The sum of these is calculated as the drift space flight velocity v ₀ of the center beam.
To obtain the total flight time T. Here, T = T (k) is set, and T (k) is exponentially expanded with respect to k. Next, k = 1, and {dT (k) / dk}
By solving a simultaneous equation of _{k = 1} = 0 and {d ² T (k) / d ² k} _{k = 1} = 0, a complete quadratic convergence condition can be obtained. And γ
Given a real value of ≠ 0, α ₁ , α, β and ρ are determined, and the values of U ₀ , U ₁ , U ₂ , U ₄ and U ₅ are determined.

Now, the ion optical parameter of TOF d ₁ =
6.5 mm, d ₂ = 58.5 mm, d ₃ = 1000 m
m, d ₄ = 219 mm, f = 0.53846, the post-accelerator parameter γ = 0 (d ₅ = 0), and γ
= 0.5 to 3.0 are shown in Table 1.

[0020]

[Table 1] The parameters in this table are such that the primary and secondary convergence coefficients for the ion spread (δ) at the single-stage acceleration part of the ion are always 0.
Condition. The numerical values in the rows corresponding to δ ³ , δ ⁴ , δ ⁵ indicate the third-order or higher order aberration coefficients for δ. L is the calculation result of the effective flight distance, and the unit is mm.

From Table 1, changes in the value of the post-acceleration coefficient γ
To satisfy the perfect quadratic convergence condition, only the value of ρ
You can see that it should be changed. Also, post-accelerator function
Of course, the effective flight distance L slightly changes.
You. On the other hand, the mass resolution {R (γ)} when γ is changed is
L and δ in Table 1^Three, Δ^Four, Δ^FiveCan be calculated from the coefficient of FIG.
Γ = 0 (no post-accelerator function) (FIG. 3 (a))
And γ = 2.0 (with post-accelerator function) (Fig. 3
The resolution obtained under the condition (b) is shown. In addition,
The horizontal axis in the figure is the initial spread (mm) of the ions. Fig. 3
As you can see, even with the post-accelerator function,
Same as without post-acceleration function according to the specified conditions
It can be seen that the resolution can be obtained. In addition, γ shown in Table 1
= Two types of parameters that greatly interlock with 0.5 to 3.0
Meter ρ (reflector voltage coefficient) and L (effective flight distance)
Is shown in FIG. As shown in Table 1, γ of α and β
Is small compared to ρ, but also
And there is no linear relationship. Therefore, the post-acceleration coefficient
Calculated from α, β, and ρ corresponding to 1: 1 U for γ
U₁, U _Two, U_FourCan be obtained if you cannot set
The resolution deteriorates. Therefore, the post-accelerator voltage U_FiveAnd ream
U moved₁, U_Two, U_FourCreate a table in advance
U according to the value of γ selected by the operator₁, U_Two,
U_FourA machine that can set the voltage of the system quickly or automatically
High-resolution specs that are always stable
It is possible to provide a TOFMS that can acquire the torque.

In the above description, the example of the vertical acceleration type has been described. However, the present invention is not limited to this, and the spread of ions in a single-stage acceleration unit such as MALDI or TOFMS is similar to that of a point light source. In other cases, the method can be applied as it is. In the above description, an example of two-stage acceleration has been described, but it is needless to say that the present invention is applicable to three or more stages of multi-stage acceleration.

[0023]

As described above, according to the present invention, α, β and ρ are not linearly related to γ and correspond to the post-acceleration coefficient γ, so that α, β and ρ can be uniquely calculated. Further, it is necessary to accurately set the voltage value of each unit derived from α, β and ρ, and if the voltage value of each unit can be set accurately corresponding to γ, the mass obtained using the post-accelerator ion detector The resolution of the spectrum can achieve the same resolution as that obtained under the condition where the post-accelerator ion detector is not considered at all. In order to realize this in an actual TOFMS device,
U1, U2 in conjunction with the selected post-accelerator voltage,
U4 voltage is automatically calculated by a dedicated calculation routine, or a list table is prepared in advance, and a function is provided in which the voltage of each section can be automatically set in conjunction with the post-accelerator voltage desired by the measurer. By combining power supplies, this ensures that a stable, high-resolution TOFMS spectrum is always obtained, even for the desired mass range and in consideration of a decrease in the degree of vacuum under analytical conditions that necessarily involve the desired external ion source. Possible conditions can be obtained quickly.

[Brief description of the drawings]

FIG. 1 is a diagram showing a basic configuration of time-of-flight mass spectrometry of the present invention.

FIG. 2 is a basic configuration diagram showing a voltage and a power supply to be supplied to each unit when the ion to be analyzed is positive.

FIG. 3 γ = 0 (no post-acceleration function) and γ =
It is a figure which shows the resolution obtained on condition of 2.0 (with a post-acceleration function), respectively.

FIG. 4 is a diagram showing behaviors of two kinds of parameters ρ (reflector voltage coefficient) and L (effective flight distance).

[Explanation of symbols]

DESCRIPTION OF SYMBOLS 1 ... External ion source, 2 ... Ion reservoir, 3 ... Push-out plate, 4, 5, 7, 8, 10 ... Grid, 6 ... T
OFMS spectroscopy unit, 9: reflector unit, 11: ion detector, 12: center of ion reservoir.

Claims (1)

[Claims] 1. A time-of-flight mass spectrometer in which ions are flown from an ion reservoir by a multi-stage acceleration field and re-accelerated and detected near an ion detector, wherein a secondary convergence condition is satisfied according to a re-acceleration voltage. A time-of-flight mass spectrometer characterized in that the voltage of each acceleration field is set.