WO2015169184A1

WO2015169184A1 - Mass calibrator ionization and introduction device

Info

Publication number: WO2015169184A1
Application number: PCT/CN2015/078175
Authority: WO
Inventors: 王睿; 张小强; 沈嘉祺; 金峤; 孙文剑
Original assignee: 岛津分析技术研发（上海）有限公司
Priority date: 2014-05-08
Filing date: 2015-05-04
Publication date: 2015-11-12
Also published as: CN105097412A

Abstract

A mass calibrator ionization and introduction device for a mass spectrometer, comprising at least a first ion source for the mass calibrator ionization (1); at least a second ion source for the ionization analysis (2); independent vacuum interface devices (4) corresponding to respective ion sources; and at least an ion guiding area (51), for guiding the mass calibrator ions and the analyte ions into a quality detection analysis area (52) connected to the ion guiding area (51); wherein the first ion source (1) is in a subatmospheric environment, and the second ion source (2) is in an atmospheric environment. A low pressure environment can more effectively enhance the ionization efficiency and the ion transmission efficiency compared with an atmospheric pressure environment; ensure the mass spectrum signal strength of the mass calibrator and reduce its amount in order to reduce the contamination caused by the mass calibrator to the subsequent stage of the mass spectrum; the respective independent ion sources and vacuum interface devices of mass calibrator and the analyte also avoid the interference caused by the mass calibrator to the analyte and the contamination of the analyte vacuum interface device.

Description

Mass calibrator ionization and introduction device

Technical field

The present invention relates to the field of mass analysis technology, and in particular to a mass calibration ionization and introduction device.

Background technique

Generally, when mass calibration is performed on the mass spectrometer, the mass calibrator is introduced by an external standard method or an internal standard method. The external standard method is to introduce the analyte and the mass calibrator into the mass spectrometer at different times. The internal standard rule is to mix the analyte and mass calibrant into a solution and introduce it into the mass spectrometer. The advantage of the internal standard method over the external standard method is that it can eliminate the fluctuations caused by the instrument running at different times. However, the disadvantage of the internal standard method is that the analyte and the mass calibrant must be mixed together and introduced into the mass spectrometer. In the process of ionization of the analyte and the mass calibrant, the two will mutually produce ionization inhibition, interference and other corresponding negative effects, affecting the mass spectrometric detection of the analyte itself.

Some quality calibrant ionization and introduction devices have been developed today, which have improved the shortcomings of the internal standard method and the external standard method. For example, people separate the mass calibrator from the ion source of the analyte to reduce the mutual interference caused by simultaneous mixing between the two.

For example, U.S. Patent No. 6,410,915 B1 is to place a plurality of electrospray or other atmospheric ion sources at the mass spectrometer inlet. The vacuum interface device of the mass spectrometer can selectively align the ion source used to effect ionization and introduction of the mass calibrant separately from the analyte.

Similar patents are also available in U.S. Patent No. 6,657,191, U.S. Patent No. 6,541,768 B2, U.S. Patent No. 6,507,073 B1, U.S. Patent No. 7,399,961 B2, and U.S. Patent No. 6,784,242 B2. These patents employ ion sources at multiple atmospheric pressures to effectively separate the mass calibrant and analyte from ionization and into the mass spectrometer. However, in these patents, the mass calibrators and analytes are introduced into the mass spectrometer by the same vacuum interface device, which inevitably causes contamination of the mass calibrator in the vacuum interface portion, thereby bringing the corresponding matrix effect to the analyte detection. , affecting the detection sensitivity and detection limit of the analyte. And in these inventive techniques, the mass calibrator and the ion source of the analyte are both in adjacent location regions or even in the same predetermined chamber. This easily causes interference problems between the electric field and the airflow between the ion sources, thereby affecting the stability of the mass spectrometer detection.

Although, as in U.S. Patent No. 6,465,776 B1, a multi-channel vacuum interface device is adopted, which will come from Samples of different electrospray ion sources were introduced into the mass spectrometer through different vacuum interface devices. This avoids contamination of the vacuum interface device by different samples. However, since these vacuum interface devices are integrated into one total vacuum interface device, and each electrospray ion source must be adjacent to its corresponding interface, each electrospray ion source must be adjacent in physical distance. This does not solve the problem of mutual interference between the analyte ion source and the mass calibrator ion source. Moreover, the invention is also limited to electrospray ion sources, and does not take into account molecules that cannot be used for electrospray ionization, such as non-polar molecules, which have certain limitations for analyzable samples.

Based on the above factors, the problem of mutual interference between ion sources under adjacent atmospheric pressure is solved by separating the ion source of the analyte and the mass calibrator from the physical distance. For example, U.S. Patent No. 7,385, 190 B2, U.S. Patent No. 7,790, 905 B2, and Chinese Patent Publication No. CN100429518C, and the publication of the journal of Analytical Chemistry (Anal. Chem. 2007, 79, 5711-5718), all by separating the ion source of the analyte and the mass calibrant. The analyte and mass calibrant are introduced into the mass spectrometer at a distance and then by gas flow or by converging the end of the injection capillary as a vacuum interface device. However, a disadvantage of these inventive techniques is that the mass calibrant and analyte ultimately still need to enter the mass spectrometer through the confluent injection capillary. This never solves the matrix effect that mass calibrators can bring to analyte detection.

In addition, U.S. Patent No. 6,797,947 B2, 6,649,909 B2, and British Patent No. 2,424,219, utilizes a method of ionization under vacuum to directly carry the mass calibrant into the ion focusing device for ionization by air flow guiding. This approach avoids the matrix effect of the mass calibrant on the analyte. However, it also brings more serious pollution to the ion focusing device. And the samples that can be ionized in a higher vacuum environment are very limited. Because the mass calibrant needs to be vaporized, it enters the ion focusing device for ionization as the gas flow is directed. This makes it impossible for some samples that are not easily vaporized, such as peptide compounds, proteins, etc., to be used. The mass calibrators that are applicable in this way are very limited. In addition, since the ion source of the mass calibrator is in the vicinity of the ion focusing device, it also interferes with the guidance and detection of analyte ions.

Summary of the invention

In view of the above-mentioned shortcomings of the prior art, it is an object of the present invention to provide a mass calibrant ionization and introduction device for solving the contamination of the mass spectrometer in the mass spectrometer for the latter stage of the mass spectrometer, and the substrate for the analyte detection. Effects, as well as mutual interference problems between ion sources.

To achieve the above objectives and other related objects, the present invention provides a mass calibrant ionization and introduction device comprising:

At least one first ion source for mass calibrant ionization; at least one second ion source for analyte ionization; a separate vacuum interface device for each ion source; and at least one ion guiding region, The ion guiding region is configured to guide the mass calibrant ions and the analyte ions into a mass detection analysis region connected to the ion guiding region; wherein the first ion source is in an atmosphere lower than atmospheric pressure, The second ion source is in an atmospheric environment; wherein the first ion source and the second ion source respectively introduce mass calibrators and analytes into the ion guiding region through separate vacuum interface devices.

Preferably, the subatmospheric environment is a preset chamber having an internal air pressure lower than atmospheric pressure.

Preferably, the predetermined chamber is provided with a control valve for starting or stopping the transport of the mass calibrant ions to the ion guiding region.

Preferably, the ion guiding device as the vacuum interface device is connected to the preset chamber and the ion guiding region.

Preferably, the ion guiding device comprises one or a combination of an ion funnel, a multipole ion guiding device, a Q-array guide and a traveling wave guiding device.

Preferably, the mass calibrator ionization and introduction device is further connected with a mass calibrator sample desorption device, and the mass calibrator sample desorption device comprises: a sample stage under atmospheric pressure environment loading the mass calibrator, Desorbing the mass calibrator into a desorption source in the form of a gaseous ion, a gaseous molecule or an aerosol, and a guiding device for feeding the desorbed mass calibrator into the predetermined chamber; the first An ion source is disposed within the predetermined chamber for ionizing the fed mass calibrant into mass calibrant ions.

Preferably, the manner of desorption comprises one or a combination of laser, electrospray, corona beam, heating and sound waves.

Preferably, the first ion source comprises a plurality of nanoliter electrospray devices.

Preferably, the plurality of nanoliter electrospray devices respectively correspond to different types of mass calibrators, the plurality of types respectively corresponding to different mass ranges.

Preferably, the plurality of nanoliter electrospray devices correspond to at least one independent vacuum interface device, and the at least one vacuum interface device is connected to the same ion guiding region.

Preferably, the vacuum interface device respectively connected to the first ion source and the second ion source is disposed such that an angle between the central axes at the outlets of the vacuum interface devices is 0 to 90 degrees.

Preferably, the first ion source is at least two, respectively corresponding to different types of mass calibrators, and each type corresponds to a different mass range.

Preferably, the ion guiding regions are at least two, and the first ion source and the second ion source are respectively connected to different ion guiding regions.

Preferably, the first ion source in a sub-atmospheric environment comprises: an electrospray ion source, a desorbed corona beam ion source, a dielectric barrier discharge ion source, a corona discharge ion source, a chemical ionization ion source, a glow One or a combination of a discharge ion source, a laser desorption ion source, and a photoionization ion source; the second ion source in an atmospheric pressure environment includes: an electrospray ion source, a desorption corona beam ion source, and a dielectric barrier discharge ion One or a combination of a source, a chemical ionization ion source, a corona discharge ion source, a glow discharge ion source, a laser desorption ion source, and a photoionization ion source.

Preferably, the ion guiding region includes at least one ion guiding device, and the ion guiding device comprises: an ion funnel, a multipole ion guiding device, a Q-array guide, and a traveling wave guiding device. One or a combination.

Preferably, the mass detection analysis area is provided with a mass analyzer; the mass analyzer comprises: a single quadrupole mass spectrometer, a multiple quadrupole mass spectrometer, a time-of-flight mass spectrometer, a multiple quadrupole combined with a time-of-flight mass spectrometer One or a combination of Fourier transform ion cyclotron resonance and ion trap mass spectrometry devices.

Preferably, the subatmospheric pressure ranges from 0.0001 to 1 Torr, from 1 to 50 Torr, from 50 to 300 Torr, and from 300 to 700 Torr.

Preferably, the second ion source is connected to a liquid chromatography.

To achieve the above objectives and other related objects, the present invention provides a mass calibrant ionization and introduction device comprising: at least a first ion source for mass calibrator ionization; at least one for analyte ionization a dual ion source; a separate vacuum interface device for each ion source; and at least one ion guiding region for directing the mass calibrant ions and analyte ions into and with the ion guide a quality detecting analysis region of the lead region connection; wherein the second ion source is in an atmosphere below atmospheric pressure, the first ion source is in an atmospheric environment; wherein the first ion source and the second ion source respectively pass independent The vacuum interface device introduces the mass calibrant and analyte into the ion guiding region.

Preferably, the mass calibrant ionization and introduction device includes an ion guiding device as the vacuum interface device that communicates with the predetermined chamber and the ion guiding region.

Preferably, the ion guiding region comprises at least one ion guiding device, and the ion guiding device comprises: one of an ion funnel, a multipole ion guiding device, a Q-array guide and a traveling wave guiding device. Kind or combination.

Preferably, the vacuum interface device respectively connected to the first ion source and the second ion source is disposed such that an angle of a central axis at an exit of each vacuum interface device is 0 to 90 degrees.

Preferably, the second ion source in a sub-atmospheric environment comprises: an electrospray ion source, a glow discharge ion source, a dielectric barrier discharge ion source, a chemical ionization ion source, a corona discharge ion source, a desorption corona One or a combination of a beam ion source, a laser desorption ion source, and a photoionization ion source; the first ion source in an atmospheric pressure environment includes: an electrospray ion source, a desorbed corona beam ion source, and a dielectric barrier discharge ion One or a combination of a source, a chemical ionization ion source, a corona discharge ion source, a laser desorption ion source, a glow discharge ion source, and a photoionization ion source.

As described above, the present invention provides a mass calibrant ionization and introduction device for a mass spectrometer, comprising: at least one first ion source for mass calibrator ionization; at least one for analyte ionization a second ion source; and at least one ion guiding region for guiding the mass calibrant ions and the analyte ions into the mass detection analysis region connected to the ion guiding region; wherein the first ion source is at a low level In an atmospheric environment, the second ion source is in an atmospheric pressure environment. There is a separate vacuum interface device between each ion source and the ion guiding device; the low pressure environment reduces the vacuum pump load of the mass spectrometer compared to the atmospheric pressure environment, and the corresponding vacuum interface can be made. The cross-sectional area of the device may be larger than the cross-sectional area of the vacuum interface device in the atmospheric pressure environment, so that the mass calibrant ions generated in the pre-set chamber of the first ion source can enter the ion guiding region of the subsequent stage more, and the ions are reduced. The transmission loss in the vacuum interface device can effectively improve the ion transmission efficiency. Thus, using the first ion source below atmospheric pressure, a smaller amount of mass calibrator can be used with respect to the ion source at atmospheric pressure with equal ion signal intensity, thereby reducing the mass calibrator for the mass spectrometer vacuum interface. Contamination of the device. Separate ion source, preset chamber and vacuum interface device design for mass calibrators and analytes avoid mutual interference between mass calibrators and analyte ionization and transport, reducing mass calibrants for analyte detection The matrix effect eliminates the contamination of the analyte vacuum interface device by the mass calibrator while at the same time Fully implement the quality calibration of the internal standard method. It is of course also possible for the second ion source to be in a subatmospheric environment for ionization of the analyte. Thereby, the ionization efficiency and ion transport efficiency of the analyte can be improved, and it is suitable for the detection of trace analytes or analytes with low ionization efficiency.

DRAWINGS

1 is a schematic view showing the structure of an embodiment of a mass calibrant ionization and introduction device of the present invention.

2 is a schematic view showing the structure of an embodiment of the mass calibrant ionization and introduction device of the present invention.

3 is a schematic view showing the structure of an embodiment of the mass calibrant ionization and introduction device of the present invention.

4 is a schematic view showing the structure of an embodiment of the mass calibrant ionization and introduction device of the present invention.

Figure 5 is a schematic view showing the structure of an embodiment of the mass calibrant ionization and introduction device of the present invention.

Figure 6 is a schematic view showing the structure of an embodiment of the mass calibrant ionization and introduction device of the present invention.

Figure 7 is a schematic view showing the structure of an embodiment of the mass calibrant ionization and introduction device of the present invention.

Figure 8 is a schematic view showing the structure of an embodiment of the mass calibrant ionization and introduction device of the present invention.

Figure 9 is a schematic view showing the structure of an embodiment of the mass calibrant ionization and introduction device of the present invention.

Component label description

1,1a,1b,1c,1d,1e,1f,1g first ion source

2, 2a, 2b, 2c, 2d, 2e, 2f, 2g second ion source

3,3a,3b,3c,3d,3e,3f,3g preset chamber

31, 31a, 31b, 31c, 31d, 31e, 31f, 31g suction port

32a control valve

33b ion guiding device

4,4a,4b,4c,4d,4e,4f,4g vacuum interface unit

5,5a,5b,5c,5d,5e,5f,5g device body

51, 51a, 51b, 51c, 51d, 51e, 51f, 51g ion guiding area

511, 511a, 511b, 511c, 511d, 511e, 511f, 511g ion guiding device

52, 52a, 52b, 52c, 52d, 52e, 52f, 52g quality inspection analysis area

6c sample station

61c desorption source

62c catheter

detailed description

The embodiments of the present invention are described below by way of specific examples, and those skilled in the art can readily understand other advantages and effects of the present invention from the disclosure of the present disclosure. The present invention may be embodied or applied in various other specific embodiments, and various modifications and changes can be made without departing from the spirit and scope of the invention. It should be noted that the embodiments in the present application and the features in the embodiments may be combined with each other without conflict.

Example 1:

Referring to FIG. 1, the present invention provides a mass calibrant ionization and introduction device, comprising: at least one first ion source for mass calibrator ionization, at least one second ion source for analyte ionization 2. a predetermined chamber 3 of the first ion source, at least one ion guiding region 51, a vacuum interface device 4 for connecting the ion source and the ion guiding region, and a mass detecting and analyzing region 52, the ion guiding region 51 for guiding the mass calibrant ions and analyte ions into a mass detection analysis region 52 connected to the ion guiding region 51, the ion motion may refer to an arrow direction illustrated; wherein the first ion source 1 is in an environment below atmospheric pressure, and the second ion source 2 is in an atmospheric environment.

In one aspect, the first ion source 1 in a sub-atmospheric environment comprises: an electrospray ion source, a glow discharge ion source, a dielectric barrier discharge ion source, a chemical ionization ion source, a desorption corona beam ion source, and an electric One or a combination of a halo discharge ion source, a laser desorption ion source, and a photoionization ion source; wherein the space charge effect is lowered, the discharge current is increased, and the photon flight distance is increased due to the subatmospheric pressure environment, so that the electrospray ion source, Ionization efficiency and transmission efficiency of glow discharge ion source and photoionization ion source The rate has been greatly improved. Thus, the electrospray ion source, the glow discharge ion source and the photoionization ion source are preferred as the low pressure ion source; the second ion source 2 in the atmospheric pressure environment comprises: an electrospray ion source, a desorption corona beam ion One or a combination of a source, a dielectric barrier discharge ion source, a chemical ionization ion source, a corona discharge ion source, a glow discharge ion source, a laser desorption ion source, and a photoionization ion source. Preferably, in this embodiment, the first ion source 1 corresponding to the mass calibrator is placed in the preset chamber 3, and an electrospray ion source, a glow discharge ion source or a photoionization ion source is used. The use of a low-pressure environment to improve the ionization efficiency and ion transport efficiency of the mass calibrant ions, thereby reducing the amount of mass calibrator used, reducing the contamination of the mass spectrometer to the mass spectrometer after the mass calibrator, thereby reducing the mass calibrator for the analyte The matrix effect brought by the detection improves the detection sensitivity of the analyte.

In one aspect, the subatmospheric environment is a preset chamber 3 having an internal air pressure lower than atmospheric pressure, preferably but not necessarily, the preset chamber 3 includes a suction port 31 for pumping gas to change the internal air pressure, Therefore, the pump is connected through the air suction port 31 to extract the gas to adjust the internal air pressure; in addition, the first ion source 1 and the second ion source 2 respectively transmit the mass calibrant ions and the analyte through the mutually independent vacuum interface device 4. Ion to ion guiding region 51, on the one hand, the vacuum interface device 4 may be a sampling cone, a circular hole, a straight capillary or a curved capillary to completely separate the mass calibrant from the ionization and introduction process of the analyte, thereby This allows the mass calibrator to not contaminate the analyte's vacuum interface device and thus does not affect the analyte's detection sensitivity. It does not interfere with the ionization and introduction of the analyte, and improves the stability of the analyte detection; while the second ion source 2 is under atmospheric pressure, it can be placed under atmospheric pressure alone, or in a chamber connected to an atmospheric environment. .

In one aspect, the subatmospheric environment may be 0.0001 to 1 Torr, 1 to 50 Torr, 50 to 300 Torr, and 300 to 700 Torr; and preferably, the electrospray ion source corresponds to a low pressure of 1 to 300 Torr; the glow discharge ion source: 0.0001 to 300 Torr; photoionization ion source: 0.0001 to 300 Torr.

In one aspect, the second ion source 2 can be used in conjunction with a liquid chromatography.

In one aspect, a device body 5 is provided. The ion guiding region 51 and the mass detecting and analyzing region 52 may be chambers formed in the device body 5, and the ion guiding region 51 is lower in air pressure than the preset chamber 3. The air pressure is lower than the air pressure of the ion guiding region 51.

In one aspect, the ion guiding region 51 is provided with one or a combination of an ion guiding device 511, such as an ion funnel, a multipole ion guiding device, a Q-array guide, and a traveling wave guiding device. Of course, the ion guiding device 511 can also have an ion focusing effect, which is a conventional technique in the industry, and will not be further described; on the other hand, the quality detecting and analyzing region 52 may be provided with a mass detector and a mass analyzer. Said The mass analyzer is, for example, a single quadrupole mass spectrometer, a multiple quadrupole mass spectrometer, a time-of-flight mass spectrometer, a multiple quadrupole combined time-of-flight mass spectrometer, a Fourier transform ion cyclotron resonance, and an ion trap mass spectrometer. Alternatively, the mass detector is a device for obtaining an ion signal that impinges on the detector or an ion current signal that moves in the mass analyzer.

In the present embodiment, in order to reduce pollution, the vacuum interface device 4 to which the first ion source 1 and the second ion source 2 are respectively connected is disposed such that an angle of a central axis at an exit of each vacuum interface device 4 is 0 to 90 degrees (i.e., angle α as shown) can reduce the interference of mass calibrant ions on analyte ionization and introduction processes.

Example 2

As shown in FIG. 2, the vacuum interface device can be in various forms, and the vacuum interface device 4a can be a sampling cone, a circular hole, a straight capillary or a curved capillary, as shown, for example, in the figure, due to the ion guiding region 51a. The inlet is a straight straight capillary, so the vacuum interface device 4a of the predetermined chamber 3a in the vertical direction is a curved capillary, and is similar to the angle maintained between the ion sources in Embodiment 1, in this embodiment, The angle between the center line of the bent capillary outlet section, that is, the bending section, and the center line of the straight capillary tube is between 0 and 90 degrees, and can be aligned with the inlet of the ion guiding area 51a, and can satisfy the analysis. The material and the mass calibrator do not affect the efficiency of each other; in other embodiments, the second ion source 2a may also use a curved capillary as a vacuum interface device.

As shown in FIG. 3, preferably, the preset chamber 3a is provided with a control valve 32a for starting or stopping the transport of the mass calibrant ions to the ion guiding region 51a, and the control valve can utilize an electronic signal. Control, thus enabling the amount and timing of control mass calibrators to enter the mass spectrometer, enabling online real-time mass calibration.

As described above, if the mass calibrant ionization and introduction device includes: the device main body 5a provided with the ion guiding region 51a and the mass detecting analysis region 52a, the first ion source 1a is in the preset chamber 3a The ion source and the ion guiding region 51a are connected by a vacuum interface device 4a.

Example 3

As shown in FIG. 4, the main difference from the above embodiment is that, in the present embodiment, the predetermined chamber 3b includes an ion guiding device 33b leading to the ion guiding region 51b, as described above. The first ion source 1b is disposed in the preset chamber 3b, and the mass calibrant ions generated by ionization of the mass calibrant pass The ion guiding device enters into the ion guiding region 51b.

Preferably, the ion guiding device 33b comprises one or a combination of an ion funnel, a multipole ion guiding device, a Q-array guide and a traveling wave guiding device.

The ion source in a low pressure environment is used in conjunction with the ion guiding device 51b to improve the ion transport efficiency of the mass calibrant, reduce the amount of mass calibrator used, and contaminate the mass spectrometer.

Example 4:

As shown in FIG. 5, in the present embodiment, the main difference from the above embodiment is that the mass calibrant ionization and introduction device is further connected with a mass calibrator processing device, and the mass calibrator processing device includes: loading a sample stage 6c of the mass caliper for processing the mass calibrant into gaseous molecules for feeding into the preset chamber 3c, for example, the mass calibrant may be at the atmospheric pressure in the sample The stage is converted into a gaseous molecule, a gaseous ion, or an aerosol by means of a desorption source 61c (desorption may be laser, heated, electrosprayed, or sonic), and then sent to a predetermined cavity through, for example, a conduit 62c. Ionization is performed in the chamber 3c, and the first ion source 1c is disposed in the predetermined chamber 3c for ionizing the mass calibrator in the form of an aerosol, and then feeding the ion aligning region 51c. In this way, mass calibrators in the form of gaseous molecules, gaseous ions, or aerosols can be ionized more easily, thereby increasing ionization efficiency and reducing contamination of the mass spectrometer to the mass spectrometer. . At the same time, this secondary ionization method can also reduce the pre-preparation of the mass calibrator, save the preparation time of the mass calibrator, and can simultaneously place a plurality of mass calibrators corresponding to different mass ranges on the sample stage, which can be quickly replaced. Different quality calibrators for fast calibration of multiple mass ranges.

Example 5:

As shown in FIG. 6, the main difference from the above embodiment is that the ion guiding regions 51d are plural, the first ion source 1d (for the mass calibrator) and the second ion source 2d (for analysis). The ions are connected to different ion guiding regions 51d, respectively, and the mass calibrators and analyte ions enter the mass analysis and detection pleasing through different ion guiding devices.

In this embodiment, the ion guiding regions 51d are disposed on the left and right sides of the mass detecting and analyzing region 52d, respectively corresponding to the first ion source 1d and the second ion source 2d; The detection analysis area 52d is provided with vacuum interface devices respectively connecting the two ion guiding regions 51d on the left and right sides, so that the first ion source 1d and the second ion source 2d can be separated to the greatest extent, thus being effective The mutual interference between the analyte ions and the mass calibrant ions is eliminated, and the contamination of the analyte vacuum interface device and the ion guiding device by the mass calibrator is avoided, and the detection sensitivity and stability of the analyte are improved.

To further accommodate the application of multiple mass calibrators or analytes, two examples are provided below:

Example 6

As shown in FIG. 7, the main difference from the above embodiment is that the first ion source 1e has at least two, corresponding to mass calibrators of different mass ranges; both are in an atmosphere below atmospheric pressure and the respective internal air pressures are The same may be different, for example, in a plurality of preset chambers 3e that are independent of each other; in the embodiment, the first ion source 1e is two, and are respectively disposed in two different preset chambers 3e. Within the quality calibrators of different mass ranges, they can also be ionized separately under different sub-atmospheric conditions to meet the calibration requirements of different mass ranges, and can also be calibrated in different mass ranges without changing samples and preparation. Mixing the samples also reduces the mutual ionization inhibition and interference produced by the mass calibrators of different masses in the same mixed solution.

Example 7

As shown in FIG. 8, the main difference from the above embodiment is that the first ion source 1f or the second ion source 2f in the preset chamber 3f includes: a plurality of nanoliter electrospray devices; in this embodiment Inside the preset chamber 3f is a first ion source 1f comprising a plurality of nanoliter electrospray devices for ionizing the mass calibrant and delivering it to the ion guiding region 51f.

In one aspect, the plurality of nanoliter electrospray devices can be applied to ionization of mass calibrators of different mass ranges in one-to-one correspondence; on the one hand, at least one vacuum interface device is disposed in the preset chamber 3f. 4f, as shown in the drawing, the vacuum interface device 4f is at least one vacuum interface device; the plurality of nanoliter electrospray devices can be selectively turned on at different times to meet the requirements of selective mass calibration, or simultaneously The calibration of the different mass ranges is initiated; the at least one vacuum interface device is connected to the ion guiding region 51f. In the embodiment, the vacuum interface device can also be a sampling cone or a circle like the vacuum interface device 4f. Hole, straight capillary or curved capillary.

In this way, the mass calibration can be selectively performed to meet the calibration requirements of different mass ranges; the mass calibrant solutions of different masses can be simultaneously input, and the calibration of the larger mass range can be performed at one time without Replacing samples or preparing mixed samples; reducing mutual ionization inhibition and interference produced by different quality mass calibrators in the same mixed solution.

It should be noted that the features in the above embodiments 4, 6 and 7 can be used in combination, that is, the design of the mass calibrator for different mass ranges at the same time or at the same time, ionization and introduction, only need to design a preset chamber. And related devices, and those skilled in the art can easily obtain various combinations of technical solutions by the above description.

On the other hand, the second ion source (2~2f) may also be disposed under a sub-atmospheric environment, and the first ion source (1~1f) is set in an atmospheric pressure environment, as shown in the next embodiment; In the above embodiment, the second ion source (2 to 2f) and the first ion source (1 to 1f) are interchangeable, that is, the analyte can also be ionized under a subatmospheric environment. Ions, which enhance the ionization and ion transport efficiency of analytes, are suitable for the detection of trace analytes or analytes with lower ionization efficiency.

Example 8

As shown in FIG. 9, the main difference from the above embodiment is that the second ion source 2g is disposed in the preset chamber 3g, and the first ion source 1g is placed in an atmospheric pressure environment. The environment can improve the ion transport efficiency and ionization efficiency of the analyte, and can be used for the detection of trace analytes or analytes with low ionization efficiency, which improves the sensitivity of analyte detection.

Preferably, the subatmospheric pressure environment is a preset chamber 3g whose internal air pressure is lower than atmospheric pressure, and may have a suction port 31g.

Preferably, the mass calibrant ionization and introduction device may include an ion guiding device (not shown) as the vacuum interface device that communicates with the preset chamber 3g and the ion guiding region 51g; further preferably The ion guiding device (not shown) may include one or a combination of an ion funnel, a multipole ion guiding device, a Q-array guide, and a traveling wave guiding device.

Preferably, the ion guiding region 51g may include at least one ion guiding device 511g, the ion guiding device 511g includes: an ion funnel, a multipole ion guiding device, a Q-array guide, and traveling wave guiding One or a combination of devices.

Preferably, the vacuum interface device 4g to which the first ion source 1g and the second ion source 2g are respectively connected is disposed such that the central axis of the outlet of each vacuum interface device 4g is at an angle of 0 to 90 degrees (ie, The angle β in Fig. 9).

In summary, the present invention provides a mass calibrant ionization and introduction device for a mass spectrometer, comprising: at least a first ion source for mass calibrator ionization; at least one for analyte ionization a second ion source; and at least one ion guiding region for guiding the mass calibrant ions and the analyte ions into the mass detection analysis region connected to the ion guiding region; wherein the first ion source is at In an atmosphere below atmospheric pressure, the second ion source is in an atmospheric pressure environment. There is a separate vacuum interface device between each ion source and the ion guiding device; the low pressure environment reduces the vacuum pump load of the mass spectrometer compared to the atmospheric pressure environment, and the corresponding vacuum can be made. The cross-sectional area of the interface device is larger than the cross-sectional area of the vacuum interface device in the atmospheric pressure environment, so that the mass calibrant ions generated in the first ion source preset chamber can enter the ion guiding region of the subsequent stage more, reducing the ions. The transmission loss in the vacuum interface device can effectively improve the ion transmission efficiency. Thus, using the first ion source below atmospheric pressure, a smaller amount of mass calibrator can be used with respect to the ion source at atmospheric pressure with equal ion signal intensity, thereby reducing the mass calibrator for the mass spectrometer vacuum interface. Contamination of the device. Separate ion source, preset chamber and vacuum interface device design for mass calibrators and analytes avoid mutual interference between mass calibrators and analyte ionization and transport, reducing mass calibrants for analyte detection The matrix effect eliminates the contamination of the analyte vacuum interface device by the mass calibrator, while at the same time fully achieving the mass calibration of the internal standard method. It is of course also possible for the second ion source to be in a subatmospheric environment for ionization of the analyte. Thereby, the ionization efficiency and ion transport efficiency of the analyte can be improved, and it is suitable for the detection of trace analytes or analytes with low ionization efficiency.

The above-described embodiments are merely illustrative of the principles of the invention and its effects, and are not intended to limit the invention. Modifications or variations of the above-described embodiments may be made by those skilled in the art without departing from the spirit and scope of the invention. Therefore, all equivalent modifications or changes made by those skilled in the art without departing from the spirit and scope of the invention will be covered by the appended claims.

Claims

A mass calibrant ionization and introduction device, comprising:

At least one first ion source for mass calibrator ionization;

At least one second ion source for analyte ionization;

a separate vacuum interface device for each ion source;

At least one ion guiding region, the ion guiding region is configured to guide the mass calibrant ions and analyte ions into a quality detecting analysis region connected to the ion guiding region;

Wherein the first ion source is in an atmosphere below atmospheric pressure, and the second ion source is in an atmospheric environment; wherein the first ion source and the second ion source respectively calibrate mass through the independent vacuum interface device The analyte and analyte are introduced into the ion guiding region.
The mass calibrant ionization and introduction device of claim 1 wherein said subatmospheric pressure environment is a predetermined chamber having an internal gas pressure below atmospheric pressure.
The mass calibrant ionization and introduction device of claim 2, wherein the predetermined chamber is provided with a control valve for starting or stopping the transport of the mass calibrant ions to the ion guiding region.
The mass calibrant ionization and introduction device according to claim 2, comprising: an ion guiding device as the vacuum interface device that communicates with the predetermined chamber and the ion guiding region.
The mass calibrant ionization and introduction device according to claim 4, wherein the ion guiding device comprises: an ion funnel, a multipole ion guiding device, a Q-array guide, and a traveling wave guiding device One or a combination of them.
The mass calibrant ionization and introduction device according to claim 2, wherein a mass calibrator sample desorption device is coupled, the mass calibrator sample desorption device comprising: loading the mass calibrator in an atmospheric pressure environment a sample stage for desorbing the mass calibrant into a desorption source in the form of a gaseous ion, a gaseous molecule or an aerosol, and sending the desorbed mass calibrator a guiding device into the preset chamber; the first ion source is disposed in the preset chamber for processing the fed mass calibrator into mass calibrant ions.
The mass calibrant ionization and introduction device according to claim 6, wherein the manner of desorption comprises one or a combination of laser, electrospray, corona beam, heating, and sound waves.
A mass calibrant ionization and introduction device according to claim 1 or 2, wherein the first ion source comprises a plurality of nanoliter electrospray devices.
The mass calibrant ionization and introduction device according to claim 8, wherein the plurality of nanoliter electrospray device segments respectively correspond to different types of mass calibrators, each of which corresponds to a different mass range .
The mass calibrant ionization and introduction device according to claim 8, wherein said plurality of nanoliter electrospray devices correspond to at least one vacuum interface device, said at least one vacuum interface device being connected to said same ion Guide area.
The mass calibrant ionization and introduction device according to claim 1, wherein said vacuum interface device to which said first ion source and said second ion source are respectively connected are disposed such that an outlet of each vacuum interface device is provided The angle between the central axes is 0 to 90 degrees.
The mass calibrant ionization and introduction device according to claim 2, wherein the first ion source is at least two, respectively corresponding to different types of mass calibrators, each of the types corresponding to different masses. range.
The mass calibrant ionization and introduction device according to claim 1, wherein the ion guiding regions are at least two, and the first ion source and the second ion source are respectively connected to different ion guiding regions. .
The mass calibrant ionization and introduction device of claim 1 wherein said The first ion source under subatmospheric environment includes: electrospray ion source, glow discharge ion source, desorption corona beam ion source, dielectric barrier discharge ion source, chemical ionization ion source, corona discharge ion source, laser One or a combination of a desorbed ion source and a photoionization ion source; the second ion source in an atmospheric pressure environment comprises: an electrospray ion source, a desorbed corona beam ion source, a dielectric barrier discharge ion source, chemical ionization One or a combination of an ion source, a corona discharge ion source, a laser desorption ion source, a glow discharge ion source, and a photoionization ion source.
The mass calibrant ionization and introduction device according to claim 1, wherein said ion guiding region comprises at least one ion guiding device, said ion guiding device comprising: an ion funnel, a multipole One or a combination of an ion guiding device, a Q-array guide, and a traveling wave guiding device.
The mass calibrant ionization and introduction device according to claim 1, wherein the mass detection analysis region is provided with a mass analyzer; the mass analyzer comprises: a single quadrupole mass spectrometer, a multiple quadrupole One or a combination of a mass spectrometer device, a time-of-flight mass spectrometer device, a multiple quadrupole coupled time-of-flight mass spectrometer device, a Fourier transform ion cyclotron resonance, and an ion trap mass spectrometer.
The mass calibrant ionization and introduction device according to claim 1, wherein the subatmospheric pressure is in a range of 0.0001 to 1 Torr, 1 to 50 Torr, 50 to 300 Torr, and 300 to 700 Torr.
The mass calibrant ionization and introduction device of claim 1 wherein said second ion source is coupled to a liquid chromatography.
A mass calibrant ionization and introduction device, comprising:

At least one first ion source for mass calibrator ionization;

At least one second ion source for analyte ionization;

a separate vacuum interface device for each ion source;

At least one ion guiding region, the ion guiding region is configured to guide the mass calibrant ions and analyte ions into a quality detecting analysis region connected to the ion guiding region;

Wherein the second ion source is in an environment below atmospheric pressure, the first ion source is in a large Pneumatic environment;

Wherein the first ion source and the second ion source respectively introduce the mass calibrator and the analyte into the ion guiding region through the independent vacuum interface device.
The mass calibrant ionization and introduction device of claim 19, wherein the subatmospheric pressure environment is a predetermined chamber having an internal gas pressure below atmospheric pressure.
The mass calibrant ionization and introduction device of claim 20, comprising: an ion guiding device as the vacuum interface device in communication with the predetermined chamber and the ion guiding region.
The mass calibrant ionization and introduction device according to claim 21, wherein the ion guiding device comprises: an ion funnel, a multipole ion guiding device, a Q-array guide, and a traveling wave guiding device One or a combination of them.
The mass calibrant ionization and introduction device according to claim 19, wherein the ion guiding region comprises at least one ion guiding device, and the ion guiding device comprises: an ion funnel, a multipole ion guide One or a combination of a guiding device, a Q-array guide, and a traveling wave guiding device.
The mass calibrant ionization and introduction device according to claim 19, wherein said vacuum interface device to which said first ion source and said second ion source are respectively connected are disposed such that an outlet of each vacuum interface device is provided The central axis has an angle of 0 to 90 degrees.
The mass calibrant ionization and introduction device according to claim 19, wherein said subatmospheric atmosphere has a gas pressure range of 0.0001 to 1 Torr, 1 to 50 Torr, 50 to 300 Torr, and 300 to 700 Torr.
The mass calibrant ionization and introduction device according to claim 19, wherein the second ion source in a subatmospheric environment comprises: an electrospray ion source, a glow discharge ion source, and a desorption corona. One or a combination of a beam ion source, a dielectric barrier discharge ion source, a chemical ionization ion source, a corona discharge ion source, a laser desorption ion source, and a photoionization ion source; The first ion source in the environment includes: electrospray ion source, desorption corona beam ion source, dielectric barrier discharge ion source, chemical ionization ion source, corona discharge ion source, laser desorption ion source, glow discharge ion source And one or a combination of photoionization ion sources.