WO2018029918A1

WO2018029918A1 - Airflow-limiting ion introducing interface device for mass spectrometer

Info

Publication number: WO2018029918A1
Application number: PCT/JP2017/016421
Authority: WO
Inventors: Gongyu Jiang; Junsheng Zhang; Wenjian Sun
Original assignee: Shimadzu Corporation
Priority date: 2016-08-08
Filing date: 2017-04-25
Publication date: 2018-02-15
Also published as: CN107706082A; CN107706082B

Abstract

The present disclosure relates to an ion introducing interface structure of a mass spectrometer, and particularly to an airflow-limiting mass spectrometer ion introducing interface structure with a short tube structure. The ion introducing interface structure is located between an ion source in a relatively high air pressure environment at an upstream and an ion transmission electrode system region in a relatively low air pressure environment at a downstream, at least comprising a smaller-diameter airflow-constraining tube and a larger-diameter ion desolvation tube located at the downstream of the airflow-constraining tube. As compared with a traditional ion transmission interface shaped like a capillary having an equal inner diameter, the ion introducing interface structure has a better ion transmission efficiency under the same airflow-limiting condition, and meanwhile reduces low mass discrimination. In addition, when dirty actual samples are operated for a long time or the samples are pretreated weakly, the airflow-constraining tube can be cheaply and rapidly replaced, thereby increasing robustness and operation efficiency in use of the ion introducing interface structure of the mass spectrometer.

Description

AIRFLOW-LIMITING ION INTRODUCING INTERFACE DEVICE FOR MASS SPECTROMETER

The present disclosure belongs to the field of ion interface devices, and relates to a low-gas-loaded mass spectrometer ion introducing interface and a related operation method. It is a typical object of the present disclosure to improve an ion introducing efficiency of a small-caliber ion introducing interface and improve a reliability of a mass spectrum system when complicated pollution-prone samples are operated.

An atmospheric pressure interface of a mass spectrometer is of a great significance in rapid detection and application convenience of mass spectrum in actual analysis. However, for a small-size mass spectrum system, installation of rough vacuum and high vacuum pumps having relatively large pumping speeds can obviously increase a size and cost of the mass spectrum system, thereby limiting the application of the mass spectrum system. At present, an ordinary commercial standard-size mass spectrometer often uses a forepump of 8-12L/s and a two-stage or more-stage molecular pump having a pump speed of 40L/s and above to form a difference system. To reach a background air pressure of 10^-3 Pa in a vacuum chamber of a last-stage mass analyzer and perform effective gas transmission, usually to a two-stage or more-stage fore vacuum differential ion guiding device is formed in front of a mass analyzer and the values of the first two stages of air pressures of the guiding device are generally set in the vicinity of 100-1,000 Pa and 0.1-10 Pa.

A fore vacuum stage having a higher pressure of 100-1,000 Pa is directly connected to an atmospheric pressure interface. Since vacuum at this stage is distanced from an atmospheric pressure by 2-3 order of magnitudes of air pressure difference, a small-hole or capillary structure having an interface size of less than 1 mm is generally adopted at this stage. As a typical value, a forepump of 8-12L/s often corresponds to a sampling hole of about 0.5 mm or a capillary of about 0.75 mm having a length of about 100 mm. In order to adopt a relatively small and cheap vacuum system device, an atmospheric pressure interface mass spectrum system represented by a liquid mass system needs to limit an inlet airflow guidance to be coordinated with the reduction of the vacuum system. To solve this problem, the conventional mass spectrum systems mostly adopt three major means. Including,

Means A-type scheme: a multi-stage differential airflow-limiting device, for example, in U.S. patent application No. US20150214021, a Z-shaped ion conduction structure is adopted, in which two sampling cone structures (generally referred to as Skimmer), effective airflow limitation is formed through conductance series connection of two-stage off-axle sampling cones, similar to this, in US4977320, a structure in which a capillary and a sampling cone are connected in series is adopted, introduced airflow is firstly constrained by utilizing the heating capillary and simultaneously effective ion response is amplified by utilizing desolvation of the heating capillary, then a sample ion having a mass number larger than that of a background gas is selected through the coaxial sampling cone, the background gas is diffused by virtue of a Mach surface of the background has behind a capillary port to be relatively removed, and meanwhile, an opening structure of the sampling cone can avoid impingement loss caused by a side-direction diffusion generated when a high-pressure gas entering a low pressure environment.

In addition, Means B-type scheme is also adopted with a flow path interface having a relatively small airflow-limiting hole directly adopted to obtain ultra-low introducing port airflow guidance, this scheme sometimes includes directly constructing a fine capillary and/or a sampling cone on a same ion introducing interface device, for example, in US5304798, Millipore company designs a relatively thick prepositioned capillary combined with a post-positioned small-bore structure for performing airflow limitation, it is attempted to form convergent benefits on a sample airflow by utilizing retraction of a capillary port so as to enrich ions. Also, for example, in a scheme adopted by Hitachi in US5298744, a relatively long capillary structure is drilled or welded on the sampling cone so that it is attempted to combine an airflow limitation advantage of the capillary with diffusion loss limitation benefit of the sampling cone. In addition, there is also a design scheme that is applied to a TQ to Qda mass spectrum detector from a Waters company, airflow constraint is formed by a sampling cone small hole (US5756994) or a slab small hole (US8987663 or WO2015040387), in a design coordinated with a low-pumping-speed small pump, a typical size of a constraint small hole is less than 0.2 mm, which allows the adopted small hole to be easily blocked when “dirty” or high-salt samples are analyzed. To this end, in the above patent scheme, a design scheme that a small hole membrane can be replaced is also designed. The Waters company further designs a design that a section of heating tube is mounted in front of the small hole, pollutants are partially shielded in front of the small hole through a prepositioned tube having a certain length, so as to reduce a blocking probability of the small-bore membrane, and a design in US20030062474 is taken as a representative.

Furthermore, a means C-type scheme, namely, an analysis method that airflow guidance is limited in a manner of dynamically changing an interface size and charged specie airflow is introduced only when an ion mass analyzer works can be adopted. This scheme is proposed by Ouyang Z et al. from Tsinghua University at the earliest and used for a small-size portable mass spectrometry whose structure includes a rubber tube capable of being clamped which is opened only when a post-stage mass analyzer introduces ions, this scheme is further developed in a patent US92811169 from Hitachi, that is, a corner-shaped gate valve is used to replace the rubber tube, a heating and ionization assisting device is designed behind the corner-shaped gate valve to carry out desolvation operation on ions. There is another scheme in US9305759, that is, this device does not include a gas introducing interface having a size varying in real time but includes a two-branch ion introducing interface, two passages have different tube diameter lengths and sizes, a long and thin capillary is adopted to introduce an ionized sample when the device is connected to a liquid chromatography, when the device is connected to a gas chromatography, a gaseous sample is ionized through dividing the capillary into two portions and introducing a discharge voltage therebetween behind the capillary, and then a vacuum chamber first difference is introduced through a shorter pipe.

However, there is a certain limitation in the above methods. With means A-type: a multi-stage differential airflow-limiting device is adopted, since the actual pumping speed of a primary pump is not enlarged, an intermediate-stage pressure in a multi-stage difference structure needs to be set between an atmospheric pressure and a first difference ion guiding chamber, and the air pressure of the device is 3-30 times more than that of the first difference chamber. Substantially, under an air pressure of higher than 3000 Pa, it is difficult to find an effective ion focusing airflow-limiting device at present, coordination of a multi-stage sampling hole cone or a capillary with the sampling hole cone aims at just intercepting intermediate axle airflow substantially, while radial diffusion naturally generated after airflow undergoes vacuum stage can lead to proportion loss when in each difference airflow limitation stage, especially for low-mass desolvated ion species, their diffusion coefficients are relatively large.

With means B-type: a small hole airflow-limiting device is adopted, impingement loss is relatively serious, a so-called low mass discrimination phenomenon occurs, even low-mass species are completely cut off to pass, for example, when a heating capillary having an inner diameter of 0.25 mm or less and a length of 100 mm or more is adopted to transmit ions, samples having a mass number of 250 or less almost cannot be detected by a post-stage mass analyzer. When a tube-cone composite structure is adopted, if the capillary is prepositioned, heating and desolvation cannot be carried out at a position of a post-stage sampling cone because a gas is directly subjected to supersonic expansion to form a cooled airflow, if the capillary is post-positioned, low-mass ions which have been formed easily have tube inner wall impingement loss, so a form that a hole or a cone is post-positioned is adopted to perform airflow limitation of a small hole, but at this moment, it is difficult for desolvation at post stage, there is a need to perform capillary heating at the front end to remove ions. When a single-stage tiny airflow-limiting hole/tube is adopted, sampling loss caused by a small bore becomes a main factor for limiting sensitivity, if a thin-wall hole is adopted for airflow limitation, the inlet diameter of 1/4 of a traditional liquid chromatography-mass spectrum system vacuum interface has must been less than 0.15 mm, and thus, the vacuum interface is easily blocked and cannot be used when dirty pretreated-insufficient samples or high-salt substrate samples are analyzed, a single small hole has no desolvation effect, if an air curtain manner is adopted, consumed dry airflow amount is relatively large, while when the capillary is adopted for throttling, the heating inner wall of a thin and long capillary also easily allows the samples to generate impingement loss caused by radial diffusion. For a blocking problem caused when a small hole structure is used, it can be partially solved when the small hole structure becomes a consumable material, but, a hole for passing ions through in the small hole membrane needs to be singly and precisely processed, if samples are operated on a large scale, the cost of the consumable material is relatively considerable.

Furthermore, with means C-type scheme, a dynamic size interface is adopted, such an airflow interface actually works in a non-stable state, its system difficultly reaches stability of transmission airflow so as to influence a quantitative feature of a mass spectrum system and increase the complicated degree of the system, and furthermore, the fatigue damage of a valve and a tube body can limit a robustness of the system. In addition, a pulse introducing manner can exploit the full advantages of the mass analyzer working under a pulse time sequence in the aspects of transmission efficiency such as flying time, an ion trap and a static ion trap, however, for a four-pole rod, a sector mass spectrum and the like which are most widely applied to mass spectrum quantitative analysis, because this two types of mass spectrometers both work continuously, pulse introduction of samples refers to loss of sensitivity and analysis repeatability of instruments in a pulse duty ratio. And when a branched pipe is adopted to perform gating ion analysis, airflows introduced by two branches of pipes can interfere mutually on a T-shaped communicating vessel to introduce problems including flow pattern disturbance and inter-ionization.

Accordingly, in order to solve the above disadvantages of a small-caliber mass spectrum introducing interface in a mass spectrum interface, it is necessary to design a novel stable ion introducing interface to provide a low-cost and robust solution.

[PTL 1] US20150214021
[PTL 2] US4977320
[PTL 3] US5304798
[PTL 4] US5298744
[PTL 5] US5756994
[PTL 6] US8987663 & WO2015040387
[PTL 7] US20030062474
[PTL 8] US92811169
[PTL 9] US9305759

In view of the above disadvantages of the prior art, it is an object of the present disclosure to develop a mass spectrum introducing interface having low gas introducing airflow guidance and reducing sampling loss. In the above prior art, a small-caliber mass spectrum introducing interface can effectively reduce vacuum system cost of the mass spectrum system, however, introduction of the small caliber can result in serious sampling loss and further interface inner wall impingement loss on that basis. Especially for an ion interface mass spectrum system adopting a heating capillary, its transmission efficiency merit value condition can differ according to sample mass due to mass and diffusion coefficient differences of different substances, and so-called low mass discrimination benefit occurs. In order to overcome the problem, it is necessary to optimally design transmission structure parameters of the heating capillary so as to reduce the impingement loss caused by radial diffusion and solve transmission loss of high-diffusion-coefficient low-mass ions. Even though a multi-stage scheme of a post-stage sampling cone is adopted, ions which have been lost cannot be found back actually.

With respect to the above problems existing in the prior art, an inventor considers that main problems derive from a contradiction caused by high temperature requirement of a heating and desolvation process and consequent high-temperature radial diffusion. The inventor compares situations that capillary interfaces having different inner diameters perform ion transmission. Under a situation that the whole length of the adopted heating capillary is in the same inner diameter, when the inner diameter of the capillary is less than or equal to 0.3 mm, an absolute transmission intensity of melamine molecular ions having a low mass number such as 127 Th is reduced to below 1/30 that of a capillary having an inner diameter of 0.5 mm, and under the same condition, an absolute transmission of reserpine ions having a mass number of 609 Th is only reduced to about 1/6 that of the capillary having the inner diameter of 0.5 mm, and ions having a mass number of 250 Th or less almost cannot pass through heating capillary interfaces having smaller inner diameters or longer length, such as a 0.25 mm x 200 mm capillary.

However, the inventor, during optimization of an experiment, finds that when equal airflow guidance constraining condition is reached and a bore diameter and a length of an airflow-limiting capillary are reduced simultaneously, the transmission efficiency of low-mass ions can be recovered. However, this condition is not developed in one way, but, when the capillary is less than 4 mm in length or is replaced by a thin-wall hole structure, ion transmission capability is reduced instead, and an experiment result indicates that it is caused by a fact that a too-short capillary cannot effectively perform desolvation. In order to solve this problem, the inventor finds after research that a heating capillary having an enlarged inner diameter is adopted behind a heating airflow-limiting capillary so as to carry out desolvation on charged species which have not yet been subjected to desolvation, thereby improving species transmission efficiency.

A specific scheme is as follows: a smaller-diameter airflow-constraining tube and a larger-diameter ion desolvation tube located at a downstream thereof, which are directly connected, are adopted to serve as an ion introducing interface of a small-size mass spectrum system. The ion introducing interface is characterized in that the inner diameter of the ion desolvation tube at the downstream is at least 3 times that of the airflow-constraining tube at an upstream, and under the same two-end air pressure condition, the airflow guidance of the airflow-constraining tube at the upstream is at least 1/10 or less than that of the ion desolvation tube at the downstream. In order to reach effective airflow limitation on sample gas beams passing through the airflow-constraining tube, a ratio of the partial length to the maximum inner diameter of the airflow-constraining tube is larger than or equal to 10:1, and the ion desolvation tube at the downstream is additionally provided with a heating device whose available heating time is 50-1000 degrees Celsius.

Further, the airflow-constraining tube at the upstream is also additionally provided with a heating system for improving desolvation of ions inside the airflow-constraining tube and further limiting airflow guidance thereof. Charged sample airflow departing from the airflow-constraining tube can avoid the impingement loss of desolvated molecular ions therein caused by radial diffusion. When the inner diameter of the desolvation tube is 3 times or more than 3 times that of the airflow-constraining tube at the upstream, when charged ion species of 100 Th or more uses air as a flow-loading gas, ion species having an inner diameter of 10 mm or less cannot diffuse to a tube wall. However, the desolvation effect of the heating tube wall is still transmitted to an intermediate axle sample airflow through molecule-molecule collision by virtue of air having a smaller average molecular weight, thereby taking a purpose of improving the pass-through efficiency of the ion species.

As a preferred size of the airflow-constraining tube, the inner diameter thereof is 0.10-0.25 mm;

As a preferred length of the airflow-constraining tube, the length thereof is 4-30 mm;

As a preferred size of the ion desolvation tube, the inner diameter thereof is 0.5-4 mm; and

As a preferred length of the ion desolvation tube, the length thereof is 40-90 mm;

Specially, as a preferred airflow-constraining tube, the ion interface of which the downstream is directly connected to an ion guiding device whose working air pressure is 100-700 Pa has an inner diameter of 0.15-0.25 mm and a ratio of the inner diameter to the length of 1:20-1:150. As a preferred ion desolvation tube, the ion interface has an inner diameter of 0.75-1.1 mm and a ratio of the inner diameter to the length of 1:50-1:70. As a preferred temperature of the ion desolvation tube, the temperature of the ion interface is 150-400 degrees Celsius.

When the airflow-constraining tube further limits airflow guidance through heating of the tube body, the preferred heating temperature is 250-550 degrees Celsius.

In a preferred embodiment, through preferred parameter values in the above range, a 0.15 mm x10 mm airflow-limiting tube is coordinated with a 0.9 mm x 75 mm ion desolvation tube to reach an ion transmission efficiency which is about 1/10 that of a standard 0.5 mm x 84 mm ion introducing tube, and the transmission efficiency of equal-airflow-guidance 0.25 mm x 84 mm airflow-limiting tube on ions of 127 Th is only 1/60 that of the standard tube.

In a preferred embodiment, the airflow-constraining tube and the ion desolvation tube are made of stainless steel capillaries having the same outer diameter, and this structure can be processed from the same capillary so as to simplify the structure of the device.

In a preferred embodiment, the airflow-constraining tube and the ion desolvation tube form a detachable vacuum-tight connection through sealing with a thread-fastened tapered axle sleeve, wherein the airflow-constraining tube is disposable as a consumable material, so as to be changed at a low cost at any time when being polluted.

In a preferred embodiment, the airflow-constraining tube and the ion desolvation tube are connected through a thin-walled extension seal wall so as to reduce a temperature of an elastic seal ring connecting and sealing two devices.

In a preferred embodiment, a side wall of the ion desolvation tube is provided with small holes for introducing an airflow sheath to further compress a middle axle ion sample airflow.

In a preferred embodiment, the small holes introduce vapor of a volatilizable standard substance that is introduced together with the middle axle ion sample airflow to serve as an external standard or an internal standard for mass spectrum tuning.

In a preferred embodiment, when a gas is adopted to heat the airflow-constraining tube, a working temperature of a front end of the airflow-constraining tube ranges from more than 20 degrees Celsius to 550 degrees Celsius.

As mentioned above, the airflow-limiting ion introducing interface device for the mass spectrometer disclosed by the present disclosure has the beneficial effects that as compared with a traditional ion transmission interface shaped like a capillary having an equal inner diameter, the ion introducing interface device has a better ion transmission efficiency under the same airflow-limiting condition, and meanwhile reduces low mass discrimination. In addition, when dirty actual samples are operated for a long time or the samples are pretreated weakly, the airflow-constraining tube can be cheaply and rapidly replaced, thereby increasing a robustness and an operation efficiency in use of the ion introducing interface structure of the mass spectrometer.

FIG. 1 is a schematic structural diagram of a basic embodiment of an ion interface device according to the present disclosure. FIG. 2 is a structure diagram of an ion interface device mounted on a mass spectrometer and a vacuum pump device according to the present disclosure. FIG. 3 illustrates vacuum degree influence of airflow-constraining tubes having different sizes on a preceding-stage chamber 107. FIGs. 4a-4c are graphs illustrating transmission ion-temperature efficiencies of capillary interfaces having different sizes, wherein, FIG. 4a is a result of a capillary having an inner diameter of 0.5 mm and a length of 84 mm. FIGs. 4a-4c are graphs illustrating transmission ion-temperature efficiencies of capillary interfaces having different sizes, wherein, FIG. 4b is a result of a capillary having an inner diameter of 0.25 mm and a length of 84 mm. FIGs. 4a-4c are graphs illustrating transmission ion-temperature efficiencies of capillary interfaces having different sizes, wherein, FIG. 4c is a result of an airflow-constraining capilary having an inner diameter of 0.15 mm and a length of 10 mm combined with a desolvation capillary having an inner diameter of 0.9 mm and a length of 75 mm. FIG. 5 is a diagram illustrating transmission and diffusion of ions in traditional capillaries having different sizes and a composite capillary of the present disclosure, wherein for sake of clarity, the length and the width are out of a proportion. FIGs. 6a-6e illustrating a preferred size of an ion desolvation tube 102, and ion intensity-temperature response curves of three different samples (melamine 127 Th, long-effect sulfanilamide 311 Th and reserpine 609 Th). FIGs. 7a-7b illustrates ion intensity-temperature response curves of three different samples (melamine 127 Th, long-effect sulfanilamide 311 Th and reserpine 609 Th) when the length and the inner diameter of the ion desolvation tube 102 are simultaneously reduced. FIG. 8a illustrates a structure diagram of components of a tapered cutting sleeve vacuum sealing structure capable of replacing the airflow-constraining tube. FIG. 8b illustrates a structure diagram of components of a thin flange disc vacuum sealing structure capable of replacing the airflow-constraining tube. FIG. 9 illustrates relationships between optimum heating temperatures and structural sizes under airflow-constraining tubes 101 having different structures, and ion intensity responses of three different samples (melamine 127 Th, long-effect sulfanilamide 311 Th and reserpine 609 Th) under the airflow-constraining tubes having different structures. FIG. 10a illustrates a scheme that a sheath protection gas is introduced to a tube wall of a desolvation tube 102 through a side-wall microhole. FIG. 10b illustrates a scheme that a calibration sample is introduced to the tube wall of the desolvation tube 102 through a semipermeable membrane tube coated with the side wall. FIG. 11 illustrates ion enhancing effect generated by adopting a 0.15 mm x 10 mm capillary to be connected to a desolvation having a length of 75 mm and an inner diameter of 0.9 mm in series and to be coordinated with a heating enhanced electric spray source having a heating temperature up to 550 degrees, without signal discrimination of sample ion peaks except solvent ion peaks.

Implementation modes of the present disclosure will be described below by specific embodiments, and those of ordinary skill in the art can easily know other advantages and effects of the present disclosure by virtue of the content disclosed by the present specification.

Referring to FIG. 1 to FIG. 11, it is noted that structures, proportions, sizes and the like drawn in accompanying drawings of the present specification are all merely used for coordinating the content disclosed by the specification to be known and read by those of ordinary skill in the art, but not limit the limitation conditions of implementing the present disclosure, so do not have technically substantial significance, any structure modifications, change of proportion relationships or size regulation all should fall within the scope covered by the technical content disclosed by the present disclosure without influencing generated effects and achieved purposes from the present disclosure. In the meantime, terms such as “upper”, “lower”, “left”, “right”, “intermediate” and “first” cited in the specification are only convenient for clear description but not used for limiting the implementation scope of the present disclosure, change or regulation of the relative relationships thereof should also be deemed to the implementation scope of the present disclosure without a substantial changed technology content.

FIG. 1 is a typical implementation scheme of the present disclosure. This device is formed by directly connecting an airflow-constraining tube 101 having a smaller inner diameter with an ion desolvation tube 102 having a larger inner diameter, a Pt100 mode of platinum resistor 103 is bonded on the ion desolvation tube 102 to measure the temperature of the ion desolvation tube 102, and the two ends of the desolvation tube adopt a 1-48V of alternative current voltage source 104 to perform Joule heating. The platinum resistor and a heating voltage are controlled by a temperature control instrument 105 and a determined heating temperature is set.

In order to form effective air constraint on a small-size mass spectrum device, in the present disclosure, this ion interface device is connected to a mass spectrum system, as indicated in FIG. 2, a preceding-stage chamber 107 of the mass spectrum system device is extracted by a sliding vane rotary vacuum pump 106. When the pumping speed of the vacuum pump 106 is equivalent to air pumping speed of 2 litres/second, FIG. 3 illustrates the vacuum degree influence of airflow-constraining tubes having different sizes on the preceding-stage chamber 107.

It can be seen from FIG. 3 that when the inner diameter of the airflow-constraining tube 101 ranges from 0.1 mm to 0.25 mm, the proper length of the tube 101 is selected so that the pressure of the preceding-stage chamber 107 falls within a working pressure range of 100-1000 Pa. Particularly, when a four-stage rod or a deformation system 108 thereof is adopted as an ion guiding device in the chamber 107, the proper working pressure range of the ion guiding device is about 160-370 Pa, rings in the drawing point out the preferred size of the airflow-constraining tube in this air pressure range, the airflow-constraining tube generally has a proper inner diameter of 0.15-0.25 mm and a correspondingly proper length of 6-30 mm, when the smallest inner diameter of 0.10 mm is adopted, it is allowable to adopt a length of 4 mm. It can be seen from the ratio of the allowable inner diameter to the allowable length, the ratio range thereof is 1:24-1:150. When a stacked electrode guidance device is used to replace the four-stage rod to constrain ions, a larger working pressure range may be used so as to further extend the caliber limitation of the constraining tube. For example, when a so-called dipolar ion passage technology is used, the working air pressure range of the preceding-stage chamber 107 extends to 680 Pa, at this moment, an upper limit of the theoretical inner diameter of the constraining tube 101 is 0.3 mm which corresponds to a lower limit of a ratio of the inner diameter to the length of 1:20.

In order to illustrate transmission efficiency advantages of this structure on ions having different mass-to-charge ratios, FIGs. 4a-4c illustrate transmission ion-temperature efficiency graphs of capillary interfaces having different sizes. Usually, a mainstream liquid chromatograph-mass spectrometry adopts a mechanical pump of about 8 L/s as a rough vacuum stage, when the preceding-stage air pressure is 240 Pa, a 0.5 mm x 84 mm capillary interface has better ion transmission efficiency, especially under a situation that it works at the optimal desolvation temperature of 250-300 degrees. In order to reduce the pumping speed of the preceding-stage mechanical pump to 1.4 L/s, when a capillary interface whose inner diameter is reduced to 0.25 mm is adopted, a work air pressure of a post-stage vacuum chamber of the capillary interface is still 240 Pa, at this moment, the optimal transmission temperature of reserpine ions of 609 Th is reduced to 150 degrees, and the transmission temperature merit values of the lower-mass ions of 311 Th and 127 Th are reduced to 100 degrees so that transmission temperature discrimination occurs, especially, the signal proportion of lower-mass 127 Th ions to 609 Th ions is reduced from 1/10 of original size device to 1/51 so that serious mass discrimination occurs, when working is performed at 300 degrees, ion signals of 127 Th are even completely cut off and disappear.

In an experimental study, a 0.15 mm x 10 mm capillary is adopted to replace a 0.25 mm x 84 mm capillary to be used as a mass spectrum interface, the working air pressure of the post-stage vacuum chamber of the mass spectrum interface is still 240 Pa, indicating that both of two capillaries have the same airflow guidance, and FIG. 4c illustrates ion transmission features of this combined capillary interface. It can be seen that similar to a standard capillary interface, with respect to three mixed sample ions (melamine, long-effect sulfanilamide and reserpine) having different masses, three ions are the same as ions in the standard interface along with the rising of the desolvation temperature, presenting a tendency that ion signals synchronously rise along with the rising of the temperature. The signal ratio of lower-mass melamine ions 127 Th to reserpine ions 609 Th rises back to 1/16 when in a merit value, and compared with absolute signal intensity, the intensities of ion signals of 609 Th and 127 Th are improved by 50%-5 times to different extents as well. The above results indicate that under the situation of equal airflow guidance namely equal introducing flow and equal vacuum load, adoption of a structure having a stepped inner diameter facilitates reduction of ion transmission loss.

In order to reveal the reason of this ion signal improvement, FIG. 5 illustrates a transmission-diffusion situation diagram of ions having different masses in interface capillaries having different structures. It can be seen that in a common large-caliber capillary, ions arrive at the inner diameter of the tube when reaching average diffusion radius at the tail end of the capillary. While, after the inner diameter of the capillary is reduced, the ions can diffuse to a position nearby the inner wall of the tube when being in the middle of the tube to cause impingement loss, after a stepped inner diameter structure is adopted, a diffusion space is left in a radial direction for species that has been subjected to heating and desolvation, and therefore, the transmission impingement loss of the species in the desolvation tube is obviously overcome, the transmission rising of the ions is generated as indicated in FIG.4, and especially, the transmission on small ions having low masses and high diffusion coefficients are improved obviously. As the upper limit of the size of the desolvation tube 102, the tube diameter should be equivalent to a size of a Mach surface formed by supersonic expansion at the tail end of the tube 102, namely about 4 mm. Under this circumstance, ions at the tail end can completely avoid impingement lost when being subjected to supersonic expansion. But, expect for collision, an ion-containing high-speed gas and the inner wall of the desolvation tube bring influences such as deolvation favorable to signals, accordingly, it is necessary to optimize specific sizes.

FIGs. 6a-6e illustrate a preferred size of the ion desolvation tube 102, from which it can be seen that when the inner diameter of the ion desolvation tube 102 ranges from 0.5 to 1.3 mm, different kinds of ions all can obtain a certain ion passing rate without a phenomenon that ions having low mass number such as 127 Th are completely cut off in the above capillary having an equal inner diameter. However, the drawings also illustrate limitation brought by too big or too small desolvation tubes, for example, when a desolvation tube of 0.5 mm is adopted, there are a mass discrimination phenomenon and a phenomenon that ions generate impingement diffusion loss along with heating at the temperature of 120 degrees or more. As to a tube of 1.3 mm, ion signals generate plateau regions when the working temperature of the tube is less than 100 degrees, which indicates that at this moment, the heating of the tube wall on transmission ions and charged liquid drops is insufficiently, the ions cannot effectively diffuse to a position nearby the inner wall of the heating tube before departing from the whole device, and realize effective desolvation insofar as needing a temperature of 300 degrees or more. This is unfavorable for designing a detachable structure of an ion interface and a vacuum chamber, because when the temperature is 300 degrees or more, there are no reliable elastic materials (such as rubber) to perform sealing and unconspicuous discharge of discomposed gas. Thus, the desolvation tubes 102 having an inner diameter of 0.75-1.1 mm are all included within the optimal size range.

It is noted that when the tube diameter of the ion desolvation tube 102 is reduced, the impingement loss of the ions can be avoided as well by limiting the length of the ion desolvation tube 102. FIGs. 7a-7b illustrate this effect that when the inner diameter of the tube 102 is reduced from 0.90 mm to 0.75 mm, the length of the tube 102 is decreased from 75 mm to 60 mm, and similar transmission ion efficiency and relative proportions of various ions can be realized as well. It can be seen that there is a certain significance for maintaining the length-to-inner diameter ratio of the ion desolvation tube 102 to be a constant value. In an experiment, it can be found that when the inner diameter-to-length ratio of the tube is about 1:50-1:70 (approximately corresponding to a tube length of 40-90 mm), reduction of ion signals on the desolvation tube due to heating temperature and impingement loss is not obvious. At the same time, since the transmission efficiency of the desolvation tube can be promoted insofar as a proper temperature is needed, a proper heating temperature range which is 150-300 degrees Celsius is shown as a gentle section of the ion signal in FIG. 6b.

In addition, it is further noted from FIGs. 6a-6e that a wider inner diameter of the ion desolvation tube corresponds to a higher heating temperature, which results from a fact that direct high-efficiency wall surface collision heating is replaced by a lower-efficiency radiation heating process. As to a situation that the size of the desilvation tube 102 reaches 4 mm, the highest heating temperature being up to 1000 degrees Celsius can also be used actually, but at this moment, it is required for some means to separate a heating part of the tube from a vacuum sealing part in space. At this moment, since a heating effect is relatively obvious, a temperature-signal straight section occurs, resulting from reduction of space gas molecule number density caused by heating (which is inversely proportional to an absolute temperature of gas) and balance effect of heating and desolvation. It is noted that the reduction of the gas molecule number density can also be used for providing stronger airflow-constraining effect to the constraining tube 101.

FIG. 8a illustrates an improved ion interface device realizing this structure. In this structure, a structure of a so-called Swagelok metal seal axle sleeve 110 is adopted to replace welding in a basic scheme to realize a scheme of a replaceable airflow-constraining tube 101. The axle sleeve structure 110 is composed of a tapered protective sheath 1101 and an external thread cone hole 1102, and a firm vacuum seal structure is formed by a clamp nut 1103. In this scheme, the device is additionally provided with a heating block 111, which is tightly coordinated with the outer diameter of the airflow-constraining tube 101 so as to realize the additional heating of the airflow-constraining tube. As a variant, thermal conduction and heat transmission control of the heating block 111 and the constraining tube 101 can be realized through air curtain airflow 112 therebetween. Another function of the air curtain airflow 112 is that charged liquid drops formed by an ion source such as electric spray ionization source 113 in the drawings are subjected desolvation before entering the introducing interface of the tube 101, and simultaneously, the air curtain can blow away dirty large-size liquid drops so as to avoid direct pollution of the airflow-constraining tube. To make an O-shaped ring seal structure adapt to a situation that the temperature of the desolvation tube 102 is more than 300 degrees, a thin-wall round tube stepped thermal sink 114 is welded outside the desolvation tube 102 to provide vacuum seal, and the air curtain airflow 112 can be used for precooling the vacuum sealing surface of the thermal sink 114 in order to further reduce the failure risk of the O-shaped ring.

In addition, another method can also be used to reduce the failure risk of an airtight structure at high temperature. As indicated in FIG. 8b, a thin-wall plain film 1012 can be welded outside the replaceable airflow-constraining tube 101. Because the thin-wall plain film 1012 has a small section thickness (the typical size of the narrowest position is 0.2-0.5 mm), even if it is made of a metal member such as stainless steel, the thermal conductivity of the thin-wall plain film 1012 can be controlled in a reasonable acceptance range, so that a O-shaped ring tightly connected to the plain film is tightly combined with the plain film to form vacuum seal. Similarly, this thin-wall structure 1022 can also be formed outside the desolvation tube 102, so that the O-shaped ring can be effectively fixed, and is not heated and melted. This structure can be popularized to any situations using an elastic seal ring. For a purpose that the thin-wall structure is capable of effectively limiting heat transmission, the so-called thin-wall thickness should be controlled to half or less than the size of the outer diameter of the airflow-constraining tube 101.

FIG. 9 illustrates optimal heating temperatures under the airflow-constraining tubes 101 having different structures. When the heating temperature rises up to 500 degrees, a structure of a tube 101 having an inner diameter of 0.25 mm may also be adopted, its ion signal may be improved by about 2-3 times relative to a structure of 0.15 mm adopted at room temperature and a slightly higher temperature. In the meantime, a structure for sealing the metal axle sleeve can also improve coaxial coordination feature of the tube 101-the tube 102, for example, compared with a situation that a thick-wall rubber tube is used for sealing, the ion signal may rise by about 1.5 times. When the airflow guidance of the airflow-constraining tube is limited further through heating of the tube body, the preferred heating temperature of the airflow-constraining tube is 250-550 degrees Celsius.

It is further noted that different from a structure that a thin-wall membrane hole or a cone hole is adopted to form airflow limitation in the above schemes, a short capillary airflow-limiting device adopted in this scheme can additionally obtain the desolvation gain of the ion signals, for example, a situation indicated in a table 1 that a comparison experiment is made to the thin-wall hole airflow limitation and an airflow-constraining tube having an inner diameter of 0.15 mm and a length of 10 mm. As to polyethylene glycol/propylene glycol polymer ions of from 256 Th to 1004 Th, when the airflow-constraining tube is replaced with an equal-airflow-guidance small hole having an inner diameter such as 0.12 mm, all of the ion signals generate 3-4 times of signal reduction. An approximate square relationship of ion response and inner diameter represented by the small hole structure and a multi-time parallel experiment result by changing a small hole processing manner indicate that this difference is not caused by the structure error of the processed small hole, and is indeed transmission advantage brought by the capillary airflow-limiting structure.

In addition, some variations can be made to this device so as to introduce new functions and effects. For example, as indicated in FIG. 10a, a plurality of small holes 1021 can be formed in a tube wall of a desolvation tube 102 so as to introduce sheath airflow outside a main axle airflow for avoiding ion loss when directly bombarding the inner wall of the desolvation tube, and a principle of this method is mainly achieved by a fact that the endosmosis of the sheath airflow compresses intermediate axle ion-containing airflow therein. Another variation illustrated in FIG. 10b uses a PDMS (polydimethylsiloxane) tube 1022 having a semipermeable membrane micropore structure to replace the small holes to replace the small hole to introduce gas from the outside to form gas sheath. According to different design requirements, the thickness of the semipermeable membrane may be selected between 0.002 mm and 1 mm, and generally, in order to facilitate sealing, a tube-shaped membrane capable of being shrunk inwardly by heating may be adopted or a complete structure is realized by using a plane membrane added with a proper clamp member. Simultaneously, a correction sample 1023 may be introduced by the semipermeable membrane without disturbing smoothness of the inside of the ion introducing interface, thereby taking an effect of correcting a post-stage mass spectrum system in real time in no need of replacing correction liquid and ion source connection. Components of available correction liquid include but are not limited to molten metal or alloy thereof, silicon grease, fluorpolyether, polyols, unsaturated advanced aliphatic hydrocarbon and halogeneated products thereof, ion liquid and other available compounds having proper boiling ranges, the small hole or semipermeable membrane structure introduces vapor of a volatilizable standard substance that is introduced together with the middle axle airflow to serve as an external standard for mass spectrum tuning, sample ions to be analyzed are introduced together with the vapor of the standard substance so as to serve as an internal standard for correcting the mass precision and intensity of the mass spectrum constantly.

In addition, it is also noted that experiments prove that this ion interface device not only can inhibit ion radial diffusion impingement loss brought by heating inside but also can obtain the increasing of ion signals and does not introduce low-mass ion discrimination loss brought by a small-flow air pressure interface when an electric spray ionization source for external heating or an atmospheric pressure chemical ionization source is used. FIG. 11 illustrates an effect generated by adopting a 0.15 mm x 10 mm capillary airflow tube to be connected to a 75 mm x 0.9 mm desolvation tube in series and to be coordinated with a room-temperature electric spray source and a heating enhanced electric spray source having a heating temperature being up to 550 degrees. An ionization experiment result of polyethylene glycol/propylene glycol mixed sample methanol-aqueous solution indicated in FIG. 11 illustrates that signal gains of ions in a wide mass range except solvent ions (mass number 65u) are all larger than 2, and the gains of partial high-mass ions exceed half of order of magnitudes, wherein, the heating enhanced electric spray source heats spray or assisted gas through extra electric heat or other schemes to form the rising of the temperature of a capillary airflow-limiting tube inlet. It is noted that except for the highest heating temperature of 550 degrees obtained by current experiment devices, under the condition that the heating temperatures of other capillary airflow-limiting tube inlets are higher than room temperature (20 degrees Celsius), various signal ion signals can rise in different quantities, which means that this device can be adapt to various heating ion source mass spectrum interfaces.

The above embodiments merely exemplarily illustrate the principle and effect of the present disclosure, and are not intended to obstruct the present disclosure. Persons skilled in the art can make modification or change on the above embodiments without deviating from the spirit and the scope of the present disclosure. For example, a protection tube or protection cone which has no airflow-limiting function is added in front of this device, or an air dynamic adjustment lens for limiting the flow type of airflow, etc. Accordingly, all of equivalent modification or changes completed by persons skilled in the air without departing from the spirit and the technological ideas disclosed by the present disclosure are still covered by claims of the present disclosure.

Claims

An airflow-limiting ion introducing interface device for a mass spectrometer, characterized by comprising following structures:
　　an airflow-constraining tube, an opening of which is located in an ion source region in a relatively high air pressure environment at an upstream;
　　an ion desolvation tube, an outlet of which is located in an ion transmission electrode system region in a relatively low air pressure environment at a downstream, wherein,
　　a ratio of a length to a maximum inner diameter of the airflow-constraining tube is larger than or equal to 10:1,
　　a minimum inner diameter of the ion desolvation tube is 3 times or more than 3 times the maximum inner diameter of the airflow-constraining tube,
　　a length of the ion desolvation tube is larger than that of the airflow-constraining tube; and
　　a temperature control device, configured to control a temperature of the ion desolvation tube to obtain a determined temperature to remove residual solvent-ion bonding.
The airflow-limiting ion introducing interface device according to claim 1, characterized in that an available heating temperature of the ion desolvation tube at the downstream is 50-1,000 degrees Celsius.
The airflow-limiting ion introducing interface device according to claim 1, characterized in that the inner diameter of the airflow-constraining tube is 0.10-0.25 mm, and the length thereof is 4-30 mm.
The airflow-limiting ion introducing interface device according to claim 1, characterized in that the inner diameter of the ion desolvation tube is 0.5-4 mm, and the length thereof is 40-90 mm.
The airflow-limiting ion introducing interface device according to claim 1, characterized in that the downstream is directly connected to an ion guiding device with a working air pressure of 100-700 Pa; the airflow-constraining tube has an inner diameter of 0.15-0.25 mm and a ratio of the inner diameter to the length of 1:20-1:150; and the ion desolvation tube has an inner diameter of 0.75-1.1 mm, a ratio of the inner diameter to the length of 1:50-1:70 and a temperature of 150-400 degrees Celsius.
The airflow-limiting ion introducing interface device according to claim 5, characterized in that when the airflow-constraining tube further limits an airflow guidance by heating a tube body, a heating temperature thereof is 250-550 degrees Celsius.
The airflow-limiting ion introducing interface device according to claim 1, characterized in that the airflow-constraining tube and the ion desolvation tube are made of stainless steel capillaries with an equal outer diameter, and are processed from a same material block.
The airflow-limiting ion introducing interface device according to claim 1, characterized in that the airflow-constraining tube and the ion desolvation tube form a detachable vacuum-tight connection through sealing with a thread-fastened tapered axle sleeve, wherein the airflow-constraining tube is disposable as a consumable material, so as to be changed at a low cost when being polluted.
The airflow-limiting ion introducing interface device according to claim 1, characterized in that outer walls of the airflow-constraining tube and the ion desolvation tube are welded or processed to form a thin-wall structure for supporting a vacuum-tight elastic seal ring.
The airflow-limiting ion introducing interface device according to claim 1, characterized in that a side wall of the ion desolvation tube is provided with a small hole or a semipermeable membrane structure for introducing an airflow sheath to further compress a middle axle ion sample airflow.
The airflow-limiting ion introducing interface device according to claim 10, characterized in that the small hole or the semipermeable membrane structure introduces vapor of a volatilizable standard substance that is introduced together with the middle axle ion sample airflow to serve as an external standard or an internal standard for mass spectrum tuning.
The airflow-limiting ion introducing interface device according to claim 1, characterized in that when gas is adopted to heat the airflow-constraining tube, a working temperature of a front end of the airflow-constraining tube ranges from more than 20 degrees Celsius to 550 degrees Celsius.