CN102768236A - Multifunctional multi-channel ion source for mass spectrometer and mass spectrum analysis method for trace components in original sample - Google Patents

Abstract

The invention discloses a mass spectrometer multi-channel ion source and a mass spectrometry analysis method for trace components in an original sample. The ion source includes a sample ionization area composed of a high-voltage power supply, multiple nozzles and a sample plate, and at least two channels. The sample flow ejected from the second channel collides with the reagent ions ejected from the first channel to form sample ions, or the reagent ions ejected from the first channel collide with the sample in the sample tray to ionize the sample, and are introduced into the inlet capillary of the mass spectrometer in mass spectrometry. The multi-channel ion source of the present invention can be connected with common mass spectrometers such as LCQ, LTQ, TSQ, etc., so that the functions of ordinary mass spectrometers can be upgraded and powerful, so as to realize the rapid and efficient mass spectrometry analysis methods for gas, liquid, solid and colloid samples. Sensitive assay and can be used for in situ, real-time, online, non-destructive analysis in industrial or environmental processes.

Description

Mass Spectrometer Multifunctional Multi-Channel Ion Source and Mass Spectrometry Method for Trace Components in Original Samples

The present invention is a divisional application. The original application date was December 28, 2006, the application number was 200610170311.8, and the title of the invention was "multifunctional multi-channel ion source for mass spectrometer".

technical field

The invention relates to the field of analytical chemistry, in particular to an ion source of a mass spectrometer and its application.

Background technique

Mass spectrometry is a specialized science and technology widely used in various disciplines to identify compounds by preparing, separating, and detecting gas phase ions. Mass spectrometer is the basis of mass spectrometry research and application. A mass spectrometer generally includes a sample introduction system, an ion source, an ion optical system, a mass analyzer, a detector, a data acquisition and control system, a vacuum system, and the like. Professor R.Graham Cooks, an internationally renowned mass spectrometer master, believes that the heart of a mass spectrometer is an ionization source, whether it is for organic mass spectrometry or inorganic mass spectrometry. Therefore, people have made a variety of designs around ionization sources, such as electron bombardment ionization source (EI), chemical ionization source (CI), field desorption ionization source (FD), fast atom bombardment ionization source (FAB), electrospray ionization source ( ESI), Atmospheric Pressure Chemical Ionization (APCI), Matrix Assisted Laser Desorption Ionization (MALDI), etc. Among them, American scientist John B. Fenn and others won the 2002 Nobel Prize in Chemistry for their significant contributions to the development of electrospray ionization (ESI), a soft ionization source. Therefore, the development of new ion sources is of great significance to modern science, national economy and people's livelihood.

The various ionization sources that have been disclosed for organic mass spectrometry mainly include EI, ESI, APCI, MALDI, PI, etc. Although each has its own characteristics and application specificity, it is necessary to transform the sample into a specific form before ionization can be performed. . This kind of preprocessing is time-consuming and troublesome, and it is difficult to realize real-time online monitoring. The DESI source proposed by Professor COOKS in 2004 solved the problem of directly measuring the substances on the solid surface without sample pretreatment, and provided an idea for real-time online detection of complex samples. However, the sensitivity of this method is not high, it is difficult to directly analyze liquid and powder samples, and it uses harmful reagents to generate reagent ions.

Contents of the invention

The purpose of the present invention is to provide a novel multi-functional multi-channel ion source for generating ions of different substances. Using this ion source, gas, liquid, solid, colloid, suspended It has good molecular-ion and ion-ion reaction performance, and is an ideal research tool for molecular-ion and ion-ion reaction.

A multi-channel ion source for a mass spectrometer provided by the invention includes a high-voltage power supply, a nozzle and a sample disc, and also includes at least two channels and two nozzles, the first channel of which is composed of a first capillary and a discharge electrode placed therein , the end of the discharge electrode extends toward the direction of the sample ionization region to the outside of the first capillary, and the chemical ionization reagent is introduced into the first capillary, and the reagent ions obtained by the corona discharge of the discharge electrode enter the sample ionization region; the second channel It consists of a sheath gas capillary and a sample nozzle placed in it, and the injection port of the sample nozzle extends to the direction of the sample ionization area outside the sheath gas capillary, and the sheath gas capillary has a carrier gas, and the sample nozzle is loaded with a sample or auxiliary reagent , the second channel is pressurized to form a sample or reagent flow into the sample ionization region; the sample or reagent flow collides with reagent ions in the sample ionization region to form sample ions and is introduced into the inlet capillary of the mass spectrometer.

The multi-channel ion source of the mass spectrometer mentioned above includes a third channel, and the structure of the third channel is the same as that of the second channel.

In the multi-channel ion source of the mass spectrometer mentioned above, the first channel is an SDAPCI source with a discharge needle.

In the multi-channel ion source of the mass spectrometer mentioned above, the second and third channels are used alone or in combination as DESI sources.

In the multi-channel ion source of the mass spectrometer mentioned above, the channel is equipped with a heating device.

In the multi-channel ion source of the mass spectrometer described above, each channel is placed on a four-dimensionally adjustable mounting frame.

In the multi-channel ion source of the mass spectrometer described above, a sample disk is also included, and the sample disk is arranged horizontally. The distance points to the sample tray.

In the multi-channel ion source of the mass spectrometer mentioned above, the chemical ionization reagent in the first channel is argon, nitrogen or air.

In the multi-channel ion source of the mass spectrometer mentioned above, the sample to be tested is gas, liquid, solid or colloid.

The multifunctional multi-channel ion source of the mass spectrometer provided by the present invention has a corresponding interface, and can conveniently switch and connect the ion source with a mass spectrometer equipped with an ESI/APCI source. After the ionization source is configured on an ordinary mass spectrometer It will be able to realize the functions of DESI, ESI, SSI, ESSI, SDAPCI, EESI, EAPCI and many other ion sources.

On the other hand, the mass spectrometry method for trace components in the original sample of the present invention uses the multi-channel ion source for the original gas or liquid sample. During detection, a chemical ionization reagent is introduced into the first channel, and a high voltage is applied to the discharge electrode. , the sample to be tested is directly sprayed into the ionization area through the second channel without pretreatment; the sample is ionized in this area in an open space and atmospheric pressure environment, and is introduced into a mass spectrometer for detection, and the composition in the sample is obtained content in.

On the other hand, the mass spectrometry analysis method of the trace components in the original sample of the present invention is aimed at the liquid, solid or colloid sample as it is, during the detection, the sample is directly placed on the sample disk without pretreatment, and the second channel or The third channel is loaded with auxiliary reagents.

On the other hand, the mass spectrometry method of the present invention for the trace components in the solid or colloidal sample uses an ion source, the ion source includes a first channel and a sample disk, the first channel consists of a first capillary and a put therein Electrode composition, the end nozzle of the discharge electrode extends out of the first capillary and points to the sample ionization area above the sample plate, and the chemical ionization reagent is introduced into the first capillary, and the reagent ions obtained by the corona discharge of the discharge electrode enter the sample Ionization area: the sample disk is arranged horizontally, the nozzle of the first channel and the sample disk are not on a horizontal plane, but above the sample disk, and point to the sample disk at an angle and distance; the reagent ions collide with the sample to form a sample ions and are introduced into the inlet capillary of the mass spectrometer;

During the detection, the ion source is connected to the LTQ mass spectrometer, the detection sample does not need to be pretreated, it is directly placed on the sample plate, and the angle between the first channel and the sample plate, the angle between the inlet capillary and the sample plate, and the LTQ are adjusted. Mass spectrometer parameters; chemical ionization reagents are introduced into the first channel, high voltage is applied to the discharge electrode, and the reagent ions generated by the first channel collide with the sample in an open space and atmospheric pressure environment to ionize the sample and be introduced into the mass spectrometer Detection is carried out to obtain the content of the component in the sample.

The chemical ionization reagent in the first channel of the ion source is argon, nitrogen or air.

The above technical solutions show that the present invention is a multi-functional, multi-channel ion source and related interface technology that integrates the theories and technologies of DESI, APCI, and SDAPCI sources. Due to the multi-channel design and each channel and its nozzle are adjustable in three to four dimensions and point to the ionization area of the sample. At the same time, there are also sample trays for placing solid, liquid or colloidal samples. Therefore, gaseous, liquid, solid, colloidal, and powder samples can be analyzed directly without sample pretreatment. The nozzle of the first channel is ESSI/SSI/ESI/APCI source mode, which is a surface desorption atmospheric pressure chemical ionization source based on corona discharge that uses argon (or air or nitrogen) to work. In this device, it can produce Highly abundant reagent ions (such as Ar ⁺ ions or hydrated protons), these reagent ions have high ionization energy (15.7eV) and can chemically ionize most substances. Gas and liquid samples can be introduced from the second channel, atomized into small droplets at the nozzle, and then interact with reagent ions to ionize the analyte. When solid and liquid samples are placed on the sample tray, high-energy reagent ions impact the sample to ionize the analyte. These analyte ions are introduced into the mass spectrometer through the inlet capillary of the mass spectrometer for mass spectrometry analysis. Since the spraying direction of the sample in the second channel is not in a straight line with the inlet capillary of the mass spectrometer, they form a certain angle with each other, and the distance is relatively large, so the phenomenon of blockage of the mass spectrometer capillary will not be caused. Therefore, it will fundamentally guarantee the successful application of mass spectrometry in real-time online monitoring.

The nozzles of the second channel and the third channel are DESI source mode, which can be used for sample or auxiliary reagent introduction, and can also be used as DESI alone. To realize the DESI function, the central quartz capillary should be under high pressure, if it is only used to introduce the test solution (or reagent), then no high pressure should be applied.

Description of drawings

Fig. 1 is the structure and working principle diagram of dual-channel ion source of the present invention;

Fig. 2 is the structural representation of the dual-channel ion source with heating device of the present invention;

Fig. 3 is the structure and working principle diagram of the three-channel ion source of the present invention;

Fig. 4 is a schematic structural diagram of a dual-channel ion source loaded with a sample disc in the present invention.

Fig. 5 is the MS spectrogram that uses ionization source of the present invention to measure the active ingredient of Claritin tablet;

Fig. 5 A is the CID spectrogram of using ionization source of the present invention to Claritin tablet m/z383;

Fig. 6 is to use the ionization source of the present invention to the real-time monitoring primary spectrogram of trace TNT in the natural water sample;

Fig. 6A is the CID spectrum of 1ppt TNT in natural water samples using the ionization source of the present invention.

Detailed ways

Different from the existing single-channel ion source, the present invention provides a multi-channel ion source. In the existing single-channel ion source, the liquid sample to be tested needs to be vaporized, and then pass through a single channel (capillary) together with the carrier gas and be ionized, and then the ion flow is ejected from the nozzle outlet in the channel, and the ion flow is at a certain rate. The speed diffuses to the surroundings and at the same time moves towards the direction of the ion flow capillary under the action of the electric field, and enters the mass analyzer through the guidance of the ion flow capillary.

The ion source of the present invention includes at least two channels, wherein the chemical ionization reagent (argon, nitrogen or air) is loaded in the first channel (capillary). When the gas is ejected from the nozzle under high pressure, due to the central discharge The electrode generates corona discharge, which produces ionization of the reagent and enters the ionization zone, while the other channel (such as the second channel, the third channel) is loaded with the sample or auxiliary reagent to be tested, and the sample or auxiliary reagent is sprayed from the outlet of each channel. It goes out to the ionization interval and collides with the reagent ions ejected from the first channel in the ionization interval, thereby ionizing the analyte in the sample, and the analyte ions are introduced through the inlet capillary of the mass spectrometer under the action of electric field and negative pressure quality analyzer.

The multi-channel ion source of the present invention will be described in detail below with reference to the accompanying drawings. Referring to Figure 1, two channels are taken as an example to illustrate the structure and working principle of the multi-channel ion source. The ion source in this example has: the first channel (SDAPCI nozzle) I, the second channel (DESI nozzle) II, and a sample ionization region A is formed between the outlet of the first channel I, the outlet of the second channel II and the inlet capillary IV of the mass spectrometer ; Wherein, the distance between the outlet end of the first channel I and the inlet capillary IV end of the mass spectrometer is 20-80 mm, and they form a certain angle (90-160°) with each other.

The first channel (SDAPCI nozzle) I consists of a first capillary 11 and a discharge electrode 12 placed therein. The needle of the discharge electrode 12 extends toward the direction of the sample ionization region A to about 1 mm outside the first capillary 11. High-voltage power supply, chemical ionization reagent (argon, nitrogen or air) gas flow G is ionized by the corona discharge generated by the first channel I discharge electrode 12, forming a reagent ion flow into the sample ionization area A;

The second channel (DESI nozzle) II is composed of a sheath gas (or carrier gas) capillary 21 and a sample capillary 22 placed therein. The sample capillary 22 is a quartz capillary thinner than the sheath gas capillary 21, and the sample capillary 22 The injection port extends toward the direction of the sample ionization area A to the outside of the sheath gas capillary 21, the sheath gas capillary 21 is connected to nitrogen gas, and the sample capillary 22 is connected to the sample (gas or liquid); when the liquid sample is difficult to volatilize, the second channel II can be connected with an external heating device 24 Apply heat (see Figure 2). The sample passes through the sample capillary 22 to form a sample stream and injects it into the sample ionization region A;

In the sample ionization region A, the sample flow is ionized during the collision with the reagent ion flow, and the sample ions form an ion flow I, which is introduced into the mass analyzer of the mass spectrometer through the inlet capillary IV of the mass spectrometer under the action of an electric field and negative pressure middle.

In the present invention, the high-voltage power supply is provided by a 12V DC power supply, a potentiometer, and a high-voltage module, and can also be directly taken from the mass spectrometer.

Another embodiment of the present invention is that heating devices 14 and 24 are provided on the outer layers of the first channel I and the second channel II respectively, see FIG. 2 , so as to obtain better ionization effect and assist desolvation.

In another embodiment of the present invention, on the basis of the above-mentioned embodiment, the number of channels can be increased to three. Referring to FIG. Sample ionization region A. The structure and function of the third channel III can be the same as that of the second channel II, and when used in combination with the second channel II, it can be used to transport auxiliary reagents; similarly, the sample flow injected from the second channel II and the auxiliary reagent injected from the third channel III The (such as desolvation) flow collides with the reagent ion flow ejected from the first channel I in the sample ionization region A to ionize the sample, and the sample ions are introduced into the mass spectrometer mass analyzer through the mass spectrometer inlet capillary IV under the action of an external electric field middle. Similarly, the outer layer of the third channel III can also be provided with a heating device.

In another embodiment of the present invention, on the basis of the above embodiment, a sample tray is added. Referring to shown in Figure 4, the sample tray 4 is placed horizontally, the sample is loaded in the sample tray, and the first channel 1 has an angle with the sample tray 4. Similarly,

The entrance capillary IV of the mass spectrometer has an included angle with the sample disk 4 on the other side of the sample disk. In this way, the reagent ion flow emitted from the first channel I collides with the sample in the sample disk 4 to form a sample flow and enters the ionization area A. At this time, the second channel II emits an auxiliary reagent flow, which contacts or reacts with the sample flow in the ionization area A. Under the action of electric field and negative pressure, it is introduced into the mass analyzer of the mass spectrometer through the inlet capillary IV of the mass spectrometer. In the case that no auxiliary reagent is needed, this embodiment can also not use the second channel.

It can be understood that, in the various embodiments above, in order to fix and adjust the positions of the first channel I, the second channel II and the third channel III, it is necessary to set up a mounting frame, which is three-dimensional or four-dimensional adjustable, so as to Adjust the distance and angle between the channels, the channel and the sample, and the entrance capillary of the mass spectrometer to meet the detection needs of different samples.

The multi-channel ion source of the present invention can be connected with common mass spectrometers (such as: LCQ, LTQ, TSQ, etc.), so that the function of ordinary mass spectrometry can be upgraded and powerful, so as to realize the mass spectrometry analysis method for gas, liquid, solid and colloid samples. Fast, sensitive assays, and can be used for in situ, real-time, online, non-destructive analysis in industrial or environmental processes.

The use process and detection effect of the multi-channel ion source of the present invention will be described below with specific detection examples.

药片中的活性成分氯雷他定(Loratadine，FW382)Test Example 1: Determination in Positive Ion Mode

The active ingredient Loratadine (FW382) in the tablet

药片放置在样品盘上，调整好第一通道与样品盘的夹角为45-80°，联接到LTQ质谱仪上的入口毛细管与样品盘的夹角为5-10°，调节好LTQ质谱仪参数。第一通道中通入化学电离试剂为氮气（含水量为45～60％），压力为0.1～20psi，放电极加高压为3～6KV，对样品进行检测，结果见图5和图5A。图5中显示了强度很高的分子离子峰m/z383，说明该方法能够有效检测到

药片中有效成分的准分子离子峰（m/z383），并且二级质谱对m/z383的CID图（参见图5A）给出明显的m/z337峰[M+H-CH₃CH₂OH]⁺，对(m/z338)结构进行了确认，从而证明使用本发明多通道离子源进行测定的准确性。In this example it is possible to use only the first channel and the sample tray. Connect the ion source to the LTQ mass spectrometer. During the experiment, the sample will be tested

Place the tablet on the sample tray, adjust the angle between the first channel and the sample tray to be 45-80°, and the angle between the inlet capillary connected to the LTQ mass spectrometer and the sample tray to be 5-10°, and adjust the LTQ mass spectrometer parameter. The chemical ionization reagent is nitrogen (water content 45-60%) in the first channel, the pressure is 0.1-20psi, and the high voltage of the discharge electrode is 3-6KV, and the sample is tested. The results are shown in Figure 5 and Figure 5A. The highly intense molecular ion peak m/z 383 is shown in Figure 5, indicating that the method can effectively detect

The quasi-molecular ion peak (m/z383) of the active ingredient in the tablet, and the CID diagram of m/z383 (see Figure 5A) by MS/MS gives an obvious peak of m/z337 [M+H-CH ₃ CH ₂ OH] ⁺ , the (m/z338) structure was confirmed, thus proving the accuracy of the determination using the multi-channel ion source of the present invention.

In addition, it can also be seen from Figure 5 that the signal intensity obtained by this method is 4.86×10 ⁷ , while the signal intensity of the same tablet reported in Science under the same conditions detected by the DESIMS ionization source is 5×10 ⁴ . It can be seen that the detection signal intensity using the ionization source of the present invention will be greatly improved, showing that the use of the ionization source of the present invention can not only directly detect solid samples, but also has great significance for realizing online mass spectrometry detection of medicines and foods. It has a positive impact on fields such as chemical engineering, public safety and life sciences.

Detection example 2: detection of trace TNT in natural water samples.

In the detection, the chemical ionization reagent is argon gas passed into the first channel, and the discharge electrode is applied with a high voltage of 5KV, and the water sample to be tested is sprayed to the ionization area through the second channel. The analyte in the sample is ionized in this area and introduced into the mass spectrometer for detection. The results are shown in Figure 6 and Figure 6A. The results show that when the TNT content in the water sample is 1ppt, the secondary mass spectrometry of TNT can also be carried out. The detection results show that the detection sensitivity can be improved by using the ionization source of the present invention, and rapid and sensitive determination and real-time online detection of trace substances can be realized.

Two detection examples have been cited above. In addition, the present invention can also flexibly change the working mode according to the nature and state of the sample by adjusting the polarity and magnitude of the applied voltage, the distance and angle of each channel, and it is convenient to carry out The mass spectrometric determination of various samples greatly broadens the application field of existing mass spectrometers.

Claims (10)

1. the mass spectrometric analysis method of trace constituent in the former state sample; It is characterized in that,, use multichannel ion source to gas or fluid sample former state; This ion gun comprises high-voltage power supply and nozzle; Also comprise at least two passages and two nozzles, its first passage is made up of first kapillary and a discharge electrode that is placed in one, and the termination of discharge electrode extends to outside first kapillary to sample ionization district direction; And import chemi-ionization reagent in this first kapillary, the reagent ion that is obtained by the corona discharge of discharge electrode gets into the sample ionization district; Second channel is made up of sheath gas kapillary and the nozzle that is placed in one; And the injection orifice of nozzle extends to outside the sheath gas kapillary to sample ionization district direction; And this sheath gas kapillary has carrier gas; Be written into sample or auxiliary reagent in the nozzle, add and depress that second channel forms sample or reagent flows into the sample ionization district; Said sample or reagent stream form sample ions with the reagent ion collision and are introduced in the mass spectrometric inlet kapillary in the sample ionization district;

In the detection, feed chemi-ionization reagent in the first passage, discharge electrode plus high-pressure, sample to be detected need not pre-service, directly are ejected into ionized region through second channel; In open space with the normal atmosphere environment under said sample in this zone ionization, and be introduced into mass spectrometer and detect, obtain the content of this composition in sample.

2. mass spectrometric analysis method according to claim 1 is characterized in that said multichannel ion source also comprises third channel, and said third channel structure is identical with second channel, and said third channel is carried auxiliary reagent.

3. mass spectrometric analysis method according to claim 1 and 2 is characterized in that, the first passage of said multichannel ion source is the SDAPCI source with spray point.

4. mass spectrometric analysis method according to claim 2 is characterized in that, second, third passage of said multichannel ion source uses or coupling as the DESI source separately.

5. according to claim 1 or 2 or 3 or 4 described mass spectrometric analysis methods, it is characterized in that said first passage, second channel or third channel are with heating arrangement.

6. according to claim 1 or 2 or 3 or 4 or 5 described mass spectrometric analysis methods, it is characterized in that each passage of said multichannel ion source places on the four-dimensional adjustable erecting frame.

7. according to the described mass spectrometric analysis method of aforementioned arbitrary claim; It is characterized in that,, also comprise a sample disc in the said multichannel ion source to liquid, solid or colloid sample former state; Said sample disc is horizontally disposed with; The nozzle of said each passage and sample disc but above sample disc, and are pointed to sample disc with an angle and distance not on a surface level; In the detection, said sample need not pre-service, directly places on the sample disc, and said second channel or third channel are written into auxiliary reagent.

8. the mass spectrometric analysis method of trace constituent in solid or the colloid sample former state; It is characterized in that use ion gun, this ion gun comprises first passage and sample disc; First passage is made up of first kapillary and a discharge electrode that is placed in one; The termination nozzle of discharge electrode extends to outside first kapillary and points to sample ionization district, sample disc top, and imports chemi-ionization reagent in this first kapillary, and the reagent ion that is obtained by the corona discharge of discharge electrode gets into the sample ionization district; Said sample disc is horizontally disposed with, and the nozzle of said first passage and sample disc but above sample disc, and are pointed to sample disc with an angle and distance not on a surface level; Said reagent ion collision sample forms sample ions and is introduced in the mass spectrometric inlet kapillary;

In the detection, ion gun is connected on the LTQ mass spectrometer, test sample need not directly be placed on the sample disc in pre-service, adjusts the angle of first passage and sample disc, and the angle of inlet kapillary and sample disc regulates LTQ mass spectrometer parameter; Feed chemi-ionization reagent in the first passage; Discharge electrode adds high pressure; In open space, collide sample down by reagent ion that first passage produced and make sample ionsization, and be introduced into mass spectrometer and detect, obtain the content of this composition in sample with the normal atmosphere environment.

9. mass spectrometric analysis method according to claim 8; It is characterized in that; The angle of first passage and sample disc is 45-80 °, and the inlet kapillary and the angle of sample disc that are connected on the LTQ mass spectrometer are 5-10 °, and the chemi-ionization reagent that feeds in the first passage is nitrogen; Pressure is 0.1～20psi, and it is 3～6KV that discharge electrode adds high pressure.

10. according to the described mass spectrometric analysis method of aforementioned arbitrary claim, it is characterized in that chemi-ionization reagent is argon gas, nitrogen or air in the said first passage.

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