KR100664728B1 - FT-ICR MS/FT-ICR MS tandem mass spectrometer - Google Patents

Abstract

The present invention relates to a tandem mass spectrometer, and more particularly, a tandem mass spectrometer using two Fourier transform ion cyclotron resonance mass spectrometers (FT-ICR MS).

The Fourier transform ion cyclotron resonance tandem mass spectrometer of the present invention finely modulates the ion source (electrospray ion source ESI: matrix assists laser desorption ionization) and the molecular ion to be injected. An octa-pole ion transport tube (300) for splitting and transferring into a high magnetic field, a first-order Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1) for analyzing the mass of a sample, and the primary Fourier transform ion Octode ion transfer tube that delivers the primary ions selected from the cyclotron resonance mass spectrometer (FT-ICR MS1) to the next stage, the octapole ion bombardment tube and the second Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1) Octopole ion guide and Octopole collision to decompose the injected sample into smaller particles cell) and a second-order Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS2), which measures the precise mass of the sample decomposed into pieces, and a vacuum pump that maintains the vacuum of all parts. .

Fourier transform ion cyclotron resonance (FT-ICR MS / FT-ICR MS) tandem mass spectrometer configured as described above enables high-speed mass measurement with high sensitivity and resolution by accumulating the sample more precisely and accumulating again. The above-mentioned Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) measurement, separation, ion excitation and ion cooling can be used to realize more sensitive and high resolution tandem mass spectrometry. Furthermore, new analytical methods can be implemented for reactions between neutral gases and ions, ions and ions, and ions and electrons.

Fourier transform ion cyclotron resonance, mass spectrometer, tandem

Description

Fourier transform ion cyclotron resonance tandem mass spectrometer {FT-ICR MS / FT-ICR MS tandem mass spectrometer}             

1 is a schematic diagram of a typical mass spectrometer

FIG. 2 is a block diagram briefly illustrating a configuration of a Fourier transform ion cyclotron resonance (FT-ICR MS / FT-ICR MS) tandem mass spectrometer according to the present invention.

3 is a diagram of a Fourier transform ion cyclotron resonance (FT-ICR MS / FT-ICR MS) tandem mass spectrometer according to the present invention.

4 is a diagram illustrating another embodiment of a Fourier transform ion cyclotron resonance (FT-ICR MS / FT-ICR MS) tandem mass spectrometer according to the present invention.

5 is an operation diagram illustrating a mass spectrometry process using a Fourier transform ion cyclotron resonance (FT-ICR MS / FT-ICR MS) tandem mass spectrometer configured as described above.

Description of the main parts of the drawing

100: ion source, 200: skimmer

300: eight-pole ion transport tube

400: FTICR 1 (First Fourier Transform Ion Cyclotron Resonance Mass Spectrometer)

410, 710: Superconducting Electromagnet

430,730: ICR Traps

500: impingement gas injection unit 600: eight octapole collision tube

700: FTICR 2 (secondary Fourier transform ion cyclotron resonance mass spectrometer)

800: vacuum pump

The present invention relates to a tandem mass spectrometer, and more particularly, to a tandem mass spectrometer using two Fourier transform ion cyclotron resonance mass spectrometers (FT-ICR MS).

In general, a mass spectrometer is a device that determines the structure of a molecule by measuring the mass of molecular ions and fragment ions.

1 is a schematic diagram of a typical mass spectrometer.

As shown in FIG. 1, the mass spectrometer includes an ion source unit 10, an analysis unit 20, and a detection / measurement unit 30. The most commonly used methods for ionizing a sample in the ion source include electrospray ionization (ESI) and matrix assists laser desorption ionization (MALDI), and most other ionization sources are used. can do.

Mass spectrometers include ion traps, flight time type, quadrupole type, and Fourier transform ion resonance type. The mass spectrometer as described above is used alone or in combination of two or more in the form of a tandem mass spectrometer.

Conventional Fourier transform ion cyclotron resonance (FT-ICR) tandem mass spectrometers generally perform experiments in two ways. One is a spatial tandem method using two spatially separated tubes, and the other is a temporal tandem method used in the same mass spectrometer with time difference between two ion selection processes.

In spatial tandem analysis, a single ion analyzer is used to select and separate ions of interest, and the mass distribution is recorded by the ion analyzer. Quadrupole tube and ion trap tube were mainly used as mass spectrometer for separation. Most of them have very wide molecular weight selection range, which limits the selection of primary ions with high resolution.

In addition, in the temporal tandem method, the primary ion is selected in the detector Fourier transform ion cyclotron resonance (FT-ICR) trap, and then an inert gas is injected to cause collision with the primary selected ion to cause fragmentation of the molecular ion, and the fragment ion How to detect. In this case, the ambient pressure is increased by the collision-inducing gas, which reduces the cyclotron kinetic energy of the ions, leading to the disappearance of the detection signal, and consequently reducing the resolution and the signal size, thereby adversely affecting obtaining a high resolution mass spectrum.

Therefore, even though the primary ion is well selected, there is a problem that the surrounding gas must be removed before the fragment ion is detected.

The present invention has been proposed to solve and secure the above problems,

Precise primary ion selection and ion decomposition are performed in the first-order Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1), which is a separation part. By optimizing the measurement irrespective of the ion decomposition process, it is possible to improve the mass measurement accuracy and to detect very large macromolecules such as biological polymers or environmental samples with high sensitivity and to study the reaction between various types of ions. The purpose is to provide.

The present invention for achieving the above object,

 For tandem mass spectrometers,

An ion source 100 for injecting a sample to be analyzed in a gaseous state or similar state and ionizing and transferring the injected sample;

A skimmer 200 for maintaining a high pressure difference between atmospheric pressure and a vacuum state;

An octapole ion transport tube 300 for splitting the injected molecular ions into high magnetic fields;

A first Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1) 400 that selects ions, analyzes and separates masses, and selects primary ions having a specific mass among the various masses in the sample;

Collision gas injection port 500 for supplying neutral gas to the octapole collision tube;

Neutral gas is injected through the collision gas inlet before transferring the selected ions from the first Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1) to the second Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS2). An octopole collision cell 600 for decomposing the sample into smaller grains by colliding ions with each other;

Secondary Fourier transform ion cyclotron resonance mass spectrometer (FT-IC) for measuring the precise mass of primary ions decomposed into pieces through the first Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1) and the quadrupole impact tube ICR MS2) 700;

It consists of a vacuum pump 800 for maintaining the vacuum state of all the components.

Hereinafter, the present invention will be described in detail.

The tandem mass spectrometer of the present invention is the latest expensive equipment of existing mass spectrometers and is mainly used for molecular weight determination and sequencing of biopolymers. Two mass spectrometers are connected in series to select a specific ion as the first analyzer, and then to generate a collision-induced reaction to determine the molecular structure from the spectrum obtained by re-isolating the secondary decomposition ions generated by the second analyzer. Because of its high resolution, it is also used to investigate the composition of complex organometallic chemicals or to study the composition of isotope substituents.

In the present invention, the sample is injected through a sample or injection device (electrospray ion source ESI: matrix assists laser desorption ionization: MALDI) in a gas or similar state and maintains a high pressure difference. An octopole ion guide, two Fourier transform ion cyclotron resonance mass spectrometers (FT-ICR MS), and two Fourier transform ion cyclotron resonance masses, transfer the sample into a skimmer, a high magnetic field. An octopole collision cell was connected between the analyzer (FT-ICR MS). In addition, a collision gas injection port is also installed inside the ion trap, and ion manipulation such as collision cooling by converting the magnetron motion of the selected ions into a cyclotron and cooling the collision is performed by a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS). Is configured to run).

A gaseous sample of a polymer is injected into an electron spray ion source, and the injected sample is ionized in an electron spray ion source and transferred to a primary Fourier transform ion cyclotron resonance mass spectrometer through an ion transport tube, and a primary Fourier transform ion cyclotron resonance mass. The analyzer collides the sample injected through the ion transport tube with the neutral gas supplied through the collision gas inlet to generate fragment ions, or converts the magnetron movement of the selected ions into cyclotron movement to cool the collision. To perform ion operations.

In this case, in the first Fourier transform ion cyclotron resonance mass spectrometer, the ambient pressure is increased by the collision-inducing gas, which reduces the cyclotron kinetic energy of ions, causing the disappearance of the detection signal, and consequently reducing the resolution and the signal size. Even if the difference is well selected, the primary ion is selected and separated to solve the problem of removing the surrounding gas before detecting the fragment ion.

The separated primary ions are broken down more finely in the octapole impingement tube, and the decomposed primary ions are injected into the secondary Fourier transform ion cyclotron resonance mass spectrometer to improve the problem of resolution in the primary ion selection and to realize various operations. This improves the measurement accuracy and enables high sensitivity detection of trace macromolecules such as biological polymers or environmental samples.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings.

FIG. 2 is a block diagram briefly illustrating a configuration of a Fourier transform ion cyclotron resonance (FT-ICR MS / FT-ICR MS) tandem mass spectrometer according to the present invention.

3 is a diagram of a Fourier transform ion cyclotron resonance (FT-ICR MS / FT-ICR MS) tandem mass spectrometer according to the present invention.

Referring to FIG. 2, the ion source 100 injects a sample to be analyzed in a gaseous or similar state as an ionization source of a mass spectrometer, and functions to ionize and deliver the injected sample. In this case, the ionization source may use a matrix assists laser desorption ionization (MALDI) together with an electrospray ionization source (ESI).

Although not shown, the skimmer 200 is formed of a multi-stage skimmer to maintain a high pressure difference between atmospheric pressure and vacuum.

The eight-pole ion guide tube 300 functions to supply a sample injected from the electrophoresis ion 100 to a first Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1) in a high magnetic field. . The second octapole ion transport tube 300 functions to supply molecular ions to the octapole collision tube or to the first Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1).

The first Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1) 400 selects ions, analyzes and separates masses, and selects a specific mass from various masses in the sample.

Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FT-ICR MS) has higher resolution and higher sensitivity than other mass spectrometers. Fourier-converted ion cyclotron resonance masses in a high magnetic field are introduced from an ion source (electrospray ion ionization ESI: matrix assists laser desorption ionization (MALDI)) through an octopole ion guide. When it comes to the analyzer (FT-ICR MS), it injects an electric field of resonant frequency into the electrode to induce cyclotron motion in the direction perpendicular to the magnetic field and measure the image current that the ions induce to the electrode to measure the mass of various ions simultaneously and Measure accurately Therefore, it is possible to secure the accuracy of primary ion selection by using high resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrum for primary ion selection.

Referring to Figure 3 in more detail, the first Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1) is formed of a cylindrical superconducting magnet 410 and Fourier transform ion cyclotron resonance (FT-ICR) trap ( 430 is formed. When ions are transferred to the Fourier transform ion cyclotron resonance (FT-ICR) trap 430 through the octapole ion transport tube 300, an electric field of a resonant frequency is injected into an electrode to perform ionic cyclotron motion in a direction perpendicular to the magnetic field. The mass of different ions is measured simultaneously and accurately by inducing and measuring the image current induced by the ions on the electrode.

 The second Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS2) is also formed of a cylindrical superconducting magnet 710 and a Fourier transform ion cyclotron resonance (FT-ICR) trap 730 is formed inside the magnet. Its function and operation is the same as that of the first-order Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1). For more precise analysis, we can consider cylindrical magnetic superconducting magnets of high magnetic fields.

 4 is a diagram illustrating another embodiment of a Fourier transform ion cyclotron resonance (FT-ICR MS / FT-ICR MS) tandem mass spectrometer according to the present invention, and a second Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS2). The ion source 100 may be configured at the rear end of the. This is to see the reaction between ions as needed. In addition, unlike the mass spectrometer shown in FIG. 3, the ion source may be injected in the reverse direction to analyze the mass.

Referring to FIG. 2 again, the collision gas inlet 500 is a function of supplying neutral gas to the eight-pole collision tube. Neutral gas is argon, nitrogen gas, etc., for example. When the collision gas is injected, ion manipulation, such as ion fragmentation and magnetron movement of selected ions, is converted to cyclotron motion, thereby cooling the collision, can be performed.

The octopole collision cell 600 carries ions selected from the first Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1) to a second Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS2). Neutral gas (for example, nitrogen and argon) is injected through the collision gas inlet before delivery to cause ions to collide, thereby decomposing the sample into smaller grains.

The second Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS2) 700 is a plurality of pieces of ions selected by the first Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1) through the octapole collision tube Measure the precise mass of the decomposed sample.

Its configuration and function is the same as that of the first-order Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1).

The vacuum pump 800 functions to maintain the vacuum state of all components.

5 is an operation diagram illustrating a mass spectrometry process using a Fourier transform ion cyclotron resonance (FT-ICR MS / FT-ICR MS) tandem mass spectrometer configured as described above.

The assays are run in several different orders, depending on the purpose of the measurement.

First, as a general operation, a sample having various masses from the sample injection device (ESI) as shown in FIG. 5 is passed through an ion transport tube to a first Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1). From the implanted ions, only a certain mass of ions are selected and injected again into the octopole collision cell using an octopole ion guide to induce a collision with the neutral gas inside the tube. The sample is then broken down into smaller portions and then passed through an iontotube ion guide into a second Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS2), where the mass of the decomposed ions is accurately measured. do. In each operation, mass selection and measurement can be made more precise.

As another example of operation, first select and store specific ions in a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1) trap, and then neutral gas is Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1) trap. After injection into the membrane, if the kinetic energy of the ion is greatly increased at the resonance frequency, collision can be detected and fragment ions can be detected. In addition, the ions generated here may be transferred to the detection unit through a gas collision cooling process, thereby reducing the kinetic energy distribution of the ions.

Next, specific ions selected in the separation part Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1) pass through the collision tube to generate fragment ions and move these fragment ions to the detector to generate secondary fragment ions By moving to the negative position, the reaction between fragment ions and gas molecules can be observed.

 In another embodiment of the mass spectrometer using the present invention, a separation Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1) and a detector Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS2) and generated cations and anions The reaction can be separated from both Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) traps and then reacted in an octapole ion bombardment tube. That is, the reaction between polycations (proteins) and anions (OH-) or polyanions (DNA) and cations (H +), or polycations and multiple cations is also possible.

The tandem mass spectrometer using two Fourier transform ion cyclotron resonances (FT-ICR MS / FT-ICR MS) according to the present invention has a high resolution, high sensitivity detection characteristic of FT-ICR MS, and selects a specific mass, stores and neutral gas. Operation such as cooling of ions through collision with can be performed. Therefore, through the structure connecting two FT-ICR mass spectrometers, it is possible to implement the temporal tandem analysis together with the spatial tandem analysis described above and also to store the ions of the FT-ICR MS. It can produce various functions that can generate and analyze various reactions between ions and gas molecules or between ions.

In addition, FT-ICR MS can be used for measuring, separating, ion excitation, and ion cooling to realize more sensitive and high-resolution tandem mass spectrometry and furthermore to neutral gases and ions, ions and ions. In addition, new methods for the reaction between ions and electrons can be implemented.

Claims (3)

In tandem mass spectrometer An ion source 100 for injecting a sample to be analyzed in a gaseous state or similar state and ionizing and transferring the injected sample; A skimmer 200 for supporting a high pressure difference between atmospheric pressure and a vacuum state; An octapole ion transport tube (Ion guide) 300 for splitting the injected molecular ions into high magnetic fields; A first Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1) 400 that selects ions, analyzes and separates the masses, and selects primary ions having a specific mass among various masses in the sample; Collision gas injection port 500 for supplying neutral gas to the octapole collision tube; Neutral gas through the collision gas inlet before transferring the primary ions selected from the first Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1) to the second Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS2) An octopole collision cell 600 for decomposing the sample into smaller grains by injecting ions into collisions; Secondary Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS2) to measure the precise mass of the sample decomposed into pieces through the first Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS1) and the octapole collision tube 700; Fourier transform ion cyclotron resonance (FT-ICR MS / FT-ICR MS) tandem mass spectrometer, characterized in that consisting of a vacuum pump for maintaining the vacuum state of all the components. The method of claim 1, The collision gas injection port is also installed inside a Fourier transform ion cyclotron resonance (FT-ICR) trap to separate the ion operation such as collision induction and magnetron movement of selected ions into cyclotron movement to cool the collision. 4. A Fourier transform ion cyclotron resonance (FT-ICR MS / FT-ICR MS) tandem mass spectrometer, characterized in that it is configured to perform in Fourier transform ion cyclotron resonance (FT-ICR MS1). The method of claim 1 or 2 Fourier transform ion cyclotron resonance (FT-ICR MS / FT-ICR MS), characterized in that the ion source 100 can be further configured at the rear end of the second Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS2). ) Tandem Mass Spectrometer.

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