The present invention relates to the technical field of mass analysis, and more specifically to an ionization and ion introduction device for a mass spectrometer.
Mass spectrometer, as an instrument to measure the molecular mass of analyte, is often employed for the detection of complex samples, trace samples, large molecules of biological samples and the like due to features such as high sensitivity and good qualitative and quantitative function. In the mass spectrometer there is one common ionization source that generally generates ions in an atmospheric pressure environment, for example, atmospheric pressure electrospray ionization source. However, such ionization source working at atmospheric pressure has a problem that ions generated in the atmospheric pressure environment are transferred into the mass spectrometer in an extremely low proportion, usually only 1% or even lower, which greatly reduces the detection sensitivity and detection efficiency of the mass spectrometer. Thus, how to improve the transfer efficiency of ions entering a mass spectrometer is a very important problem.
Generally, people enlarges the diameter of the vacuum system interface of the mass spectrometer interconnected to the atmospheric pressure ionization source, thereby directly increasing the total number of ions entering the vacuum system of the mass spectrometer. However, this method also greatly increases the burden of the vacuum system of the mass spectrometer and increases the load of a vacuum pump. There is one other method in which the number of the vacuum system interfaces of the mass spectrometer is increased, so as to enlarge the diameter of the vacuum system interface interconnected to the atmospheric pressure ionization source and simultaneously reduce the load of the corresponding pump of the vacuum system.
For example, U.S. Pat. No. 8,642,946 provides a vacuum interface device for a mass spectrometer, which includes multiple capillaries used for forming multi-stage vacuum interfaces, so as to improve the transfer efficiency of ions without increasing the burden of the final-stage vacuum pump. However, this device is merely to improve the transfer efficiency of ions entering the vacuum interface from the atmospheric pressure interface, and can't reduce neutral solvent impurities or other gas impurities at the same time; moreover, this device is only available for the ion source device working in an atmospheric pressure environment.
U.S. Pat. No. 7,700,913 provides a scheme for separating neutral gas from gas ions, which mainly is applied to the ionization method generating gas ions by surface desorption, for example, Direct Analysis in Real Time (DART) ionization source. Therefore, this scheme is not applicable to the separation between neutral gas and charged droplets.
Similar documents include Chinese patent CN102232238A (U.S. Pat. No. 8,410,431), which focuses ions generated by an ionization source by means of the laminar flow formed by a generated air flow, thereby facilitating more ions to enter the mass spectrometer. This technology mainly is applied to the condition that an atmospheric pressure ionization source is located far away from the inlet of the mass spectrometer and the condition that an analyte has a relatively big detection area. Thus, this technology is suitable for direct-analysis ionization, for example, Desorption Electrospray Ionization (DESI).
The above technologies mainly are applicable to atmospheric pressure ionization source. However, the atmospheric pressure environment itself limits the diameter of the vacuum system interface of the mass spectrometer, thus causing a great limitation to the improvement of ion transfer efficiency.
U.S. Pat. No. 8,173,960 adopts an electrospray ionization source below atmospheric pressure. However, the outlet of the electrospray ionization source chamber at a pressure below atmospheric pressure is directly connected to the inlet of the chamber of a following-stage ion focusing guide in this technology, causing lots of neutral noises (such as solvent gas molecule) generated during the process of ionization to directly enter the next-stage ion focusing guide, thus reducing the detection signal-to-noise ratio of the instrument and also bringing a great pollution to the ion focusing guide.
In view of the drawbacks in the above existing technologies, the present invention aims to provide an ionization and ion introduction device for a mass spectrometer, which transfers an ionization source from an atmospheric pressure environment to an environment below atmospheric pressure, to further enlarge the diameter of the vacuum system interface of the mass spectrometer and improve the transfer efficiency of ions, and which has at least one transfer chamber at pressure below atmospheric pressure arranged between the ionization source chamber and an ion focusing guide chamber, to further improve the detection sensitivity of the mass spectrometer.
To achieve the above aim and other relevant aims, the present invention provides an ionization and ion introduction device for a mass spectrometer, including: an ionization source chamber at a pressure below atmospheric pressure; at least one ionization source, which is arranged in the ionization source chamber to generate ions; at least one ion focusing guide chamber, which is arranged to guide ions into a mass analysis device chamber connected therewith; at least one transfer chamber at pressure below atmospheric pressure, which is located between the ionization source chamber and the ion focusing guide chamber, including an inlet interconnected to the ionization source chamber and an outlet interconnected to the ion focusing guide chamber, wherein the pressure of the transfer chamber is lower than that of the ionization source chamber but higher than that of the ion focusing guide chamber.
According to the above ionization and ion introduction device for mass spectrometer, the transfer chamber further includes at least one vacuum pump suction port for connecting to a vacuum pump.
According to the above ionization and ion introduction device for mass spectrometer, the ionization source includes one of an electrospray ion source, a glow discharge ion source, a dielectric barrier discharge ion source, a chemical an ionization ion source, a desorption corona beam ion source, a laser desorption ion source and a photo-ionization ion source, or combinations thereof.
According to the above ionization and ion introduction device for mass spectrometer, the pressure below atmospheric pressure is from 0.0001 to 1 Torr, from 1 to 50 Torr, from 50 to 300 Torr, and from 300 to 700 Torr.
According to the above ionization and ion introduction device for mass spectrometer, the inlet of the transfer chamber interconnected to the ionization source chamber and the outlet of the transfer chamber interconnected to the ion focusing guide chamber are one of a circular hole, a capillary, a taper hole, a nozzle hole, a reducing hole and a scaling hole, or combinations thereof.
According to the above ionization and ion introduction device for mass spectrometer, a direct voltage is applied to the inlet and outlet.
According to the above ionization and ion introduction device for mass spectrometer, the ionization source is used in combination with liquid chromatography.
According to the above ionization and ion introduction device for mass spectrometer, the ion focusing guide chamber has an ion focusing guide arranged therein and includes at least one vacuum pump suction port.
Further, according to the above ionization and ion introduction device for mass spectrometer, the ion focusing guide is one of an ion funnel, a multipole rod ion guide, a Q-array ion guide and a travelling wave ion guide, or combinations thereof.
Further, according to the above ionization and ion introduction device for mass spectrometer, the mass analysis device chamber has a mass detector and a mass analyzer arranged therein and includes at least one vacuum pump suction port, wherein the mass analyzer includes one of a single-quadrupole mass spectrometer device, a multi-quadrupole mass spectrometer device, a time of flight mass spectrometer device, a multi-quadrupole time of flight mass spectrometer device, a Fourier transform ion cyclotron resonance mass spectrometer device and an ion trap spectrometer device, or combinations thereof, and the mass detector is arranged to obtain a signal of ions impacted thereon or a signal of an ion current moving in the mass analyzer.
According to the above ionization and ion introduction device for mass spectrometer, the included angle between the central axes of the ionization source and the inlet of the transfer chamber interconnected to the ionization source chamber is from 0 to 90 degrees.
According to the above ionization and ion introduction device for mass spectrometer, the included angle between the central axis of the inlet of the transfer chamber interconnected to the ionization source chamber and the central axis of the outlet of the transfer chamber interconnected to the ion focusing guide chamber is from 0 to 90 degrees.
According to the above ionization and ion introduction device for mass spectrometer, the ionization source serves as a secondary ionization source for direct sample analysis.
According to the above ionization and ion introduction device for mass spectrometer, the ionization source is applied to one of a single-quadrupole mass spectrometer, a multi-quadrupole mass spectrometer, a time of flight mass spectrometer, a multi-quadrupole time of flight mass spectrometer, a Fourier transform ion cyclotron resonance mass spectrometer and anion trap spectrometer.
According to the above ionization and ion introduction device for mass spectrometer, a porous channel is arranged between the inlet of the transfer chamber interconnected to the ionization source and the outlet of the transfer chamber interconnected to the ion focusing guide chamber.
According to the above ionization and ion introduction device for mass spectrometer, at least one electrode, to which a direct voltage and a radio-frequency voltage are applied, is arranged between the inlet of the transfer chamber interconnected to the ionization source and the outlet of the transfer chamber interconnected to the ion focusing guide chamber.
As described above, the ionization and ion introduction device for mass spectrometer provided in the present invention includes at least one ionization source located in an environment below atmospheric pressure, an ionization source chamber at a pressure below atmospheric pressure, and at least one transfer chamber at pressure below atmospheric pressure. The transfer chamber is located between the ionization source chamber and the ion focusing guide chamber, including an inlet only connected to the outlet of the ionization source chamber, an outlet only connected to the inlet of the ion focusing guide chamber, and at least one vacuum pump suction port; the pressure of the transfer chamber is lower than that of the ionization source chamber but higher than that of the ion focusing guide chamber. In particular, first, the transfer chamber is arranged to assist the ionization source chamber to realize an environment below atmospheric pressure, in which discharge current is increased or photon flight distance is increased, so that the ionization efficiency of the ionization source is greatly improved; as for the electrospray ionization source, the environment below atmospheric pressure greatly reduces the repulsion between charged droplets, making the electrospray narrower, thereby increasing the number of charged droplets per unit volume, increasing the number of charged droplets entering the next-stage vacuum chamber and improving detection efficiency. At the same time, the ionization source in the environment below atmospheric pressure can make an enlarged diameter for the inlet of the next-stage transfer chamber at pressure below atmospheric pressure interconnected to the ionization source chamber, thereby improving the transfer efficiency of charged droplets and ions; pumping the transfer chamber at pressure below atmospheric pressure through a vacuum pump can reduce the gas pressure in the ionization source chamber, without directly interfering the ionization source. Second, the transfer chamber can separate charged droplets or ions from other solvents and impurity molecules using the pressure difference between the ionization source chamber and the ion focusing guide chamber, through the special design of interface between chambers, the vacuum pumping of the transfer chamber and the aerodynamic transfer principle. Smaller neutral solvent gas molecules and other small impurity gas molecules are easily exhausted by the vacuum pump due to low mass and low inertia, while charged droplets and analyte molecules still keep forward movement due to large mass and large inertia and enter the next-stage ion focusing guide through the outlet of the transfer chamber at pressure below atmospheric pressure; therefore, the transfer chamber below atmospheric pressure can further remove solvents and impurities in the environment, thereby reducing the limit of detection of the mass spectrometer; the addition of at least one stage of vacuum chamber also can reduce the load of the vacuum pump of the final-stage vacuum chamber and facilitate the desolvation of analyte, thereby improving the detection sensitivity of the mass spectrometer.
Description of designators is as follows:
Embodiments of the present invention are described below through specific examples. Those skilled in the art may easily learn other advantages and functions of the present invention from the content disclosed in the specification. The present invention also may be implemented or applied through other different embodiments, and what details described in the present invention may be modified or changed based on different views and applications without departing from the spirit of the present invention.
It should be noted that the drawings provided in embodiments are simply to illustrate the basic idea of the present invention in a schematic way, only showing components relevant to the present invention but drawn according to the number, shape and dimension of the components during actual implementation. During actual implementation, the shape, number and proportion of each component may be changed randomly and the layout of components might be more complex.
Please refer to
In one aspect, the ionization source 1 located in an environment below atmospheric pressure includes one of 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, a laser desorption ion source and a photo-ionization ion source, or combinations thereof. Since, in the environment below atmospheric pressure, charge repulsion is reduced, discharge current is increased and photon flight distance is increased, the ionization efficiency and transfer efficiency of the electrospray ion source, the glow discharge ion source and the photo-ionization ion source are greatly improved, which makes the electrospray ion source, the glow discharge ion source and the photo-ionization ion source optimal schemes for low-pressure ionization source.
In one aspect, the ionization source located in an environment below atmospheric pressure may serve as a secondary ionization source for direct sample analysis.
In one aspect, the ionization source may be applied to one of a single-quadrupole mass spectrometer, a multi-quadrupole mass spectrometer, a time of flight mass spectrometer, a multi-quadrupole time of flight mass spectrometer, a Fourier transform ion cyclotron resonance mass spectrometer and anion trap spectrometer.
In one aspect, the pressure below atmospheric pressure can be from 0.0001 to 1 Torr, from 1 to 50 Torr, from 50 to 300 Torr, or from 300 to 700 Torr. Preferably, the pressure corresponding to the electrospray ion source below atmospheric pressure is 1 to 300 Torr, the pressure corresponding to the glow discharge ion source below atmospheric pressure is 0.0001 to 300 Torr, and the pressure corresponding to the photo-ionization ion source below atmospheric pressure is 0.0001 to 300 Torr.
In one aspect, the inlet 3 of the transfer chamber 5 interconnected to the ionization source chamber 2 and the outlet 4 of the transfer chamber 5 interconnected to the ion focusing guide chamber 7 are one of a circular hole, a capillary, a taper hole, a nozzle hole, a reducing hole and a scaling hole, or combinations thereof, to which certain direct voltage can be applied.
In one aspect, the ionization source 1 is used in combination with liquid chromatography.
In one aspect, the ion focusing guide chamber 7 has an ion focusing guide 6 arranged therein and includes at least one vacuum pump suction port 10. The ion focusing guide 6 is one of an ion funnel, a multipole rod ion guide, a Q-array ion guide and a travelling wave ion guide, or combinations thereof.
In one aspect, the other side of the ion focusing guide chamber 7 is provided with a mass analysis device chamber 8, which may have a mass detector and a mass analyzer arranged therein and include at least one vacuum pump suction port 11. The mass analyzer, for example, is one of a single-quadrupole mass spectrometer device, a multi-quadrupole mass spectrometer device, a time of flight mass spectrometer device, a multi-quadrupole time of flight mass spectrometer device, a Fourier transform ion cyclotron resonance mass spectrometer device and an ion trap spectrometer device, or combinations thereof; and the mass detector is a device configured to obtain a signal of ions impacted thereon or a signal of an ion current moving in the mass analyzer.
In this embodiment, the included angle between the central axes of the ionization source 1 and the inlet 3 of the transfer chamber 5 interconnected to the ionization source chamber 2 is from 0 to 90 degrees (that is, the included angle α shown in
In addition, the included angle between the central axis of the inlet 3 of the transfer chamber 5 interconnected to the ionization source chamber 2 and the central axis of the outlet 4 of the transfer chamber 5 interconnected to the ion focusing guide chamber 7 is from 0 to 90 degrees.
The ionization and ion introduction device for mass spectrometer may take many forms. As shown in
As shown in
As shown in
As shown in
Preferably, the inlet 3d of the first transfer chamber 5d below atmospheric pressure interconnected to the ionization source 1d, the outlet 4d of the second transfer chamber 12d below atmospheric pressure interconnected to the ion focusing guide chamber 7d, the interface opening 13d between the first transfer chamber 5d below atmospheric pressure and the second transfer chamber 12d below atmospheric pressure adopt one of a circular hole, a capillary, a taper hole, a nozzle hole, a reducing hole and a scaling hole, or combinations thereof.
To be further applicable to different applications, two embodiments are provided below.
As shown in
The porous channel 14e also can be replaced by an electrode, as shown in
As shown in
To sum up, the ionization and ion introduction device for mass spectrometer provided in the present invention includes at least one ionization source located in an environment below atmospheric pressure, an ionization source chamber at a pressure below atmospheric pressure, and at least one transfer chamber at pressure below atmospheric pressure. The transfer chamber is located between the ionization source chamber and the ion focusing guide chamber, including an inlet only connected to the outlet of the ionization source chamber, an outlet only connected to the inlet of the ion focusing guide chamber, and at least one vacuum pump suction port; the pressure of the transfer chamber is lower than that of the ionization source chamber but higher than that of the ion focusing guide chamber. In particular, first, the transfer chamber is arranged to assist the ionization source chamber to realize an environment below atmospheric pressure, in which discharge current is increased or photon flight distance is increased, so that the ionization efficiency of the ionization source is greatly improved; as for the electrospray ionization source, the environment below atmospheric pressure greatly reduces the repulsion between charged droplets, making the electrospray narrower, thereby increasing the number of charged droplets per unit volume, increasing the number of charged droplets entering the next-stage vacuum chamber and improving detection efficiency. At the same time, the ionization source in the environment below atmospheric pressure can make an enlarged diameter for the inlet of the next-stage transfer chamber at pressure below atmospheric pressure interconnected to the ionization source chamber, thereby improving the transfer efficiency of charged droplets and ions; pumping the transfer chamber at pressure below atmospheric pressure through a vacuum pump can reduce the gas pressure in the ionization source chamber, without directly interfering the ionization source. Second, the transfer chamber can separate charged droplets or ions from other solvents and impurity molecules using the pressure difference between the ionization source chamber and the ion focusing guide chamber, through the special design of interface between chambers, the vacuum pumping of the transfer chamber and the aerodynamic transfer principle. Smaller neutral solvent gas molecules and other small impurity gas molecules are easily exhausted by the vacuum pump due to low mass and low inertia, while charged droplets and analyte molecules still keep forward movement due to large mass and large inertia and enter the next-stage ion focusing guide through the outlet of the transfer chamber at pressure below atmospheric pressure; therefore, the transfer chamber at pressure below atmospheric pressure can further remove solvents and impurities in the environment, thereby reducing the limit of detection of the mass spectrometer; the addition of at least one stage of vacuum chamber also can reduce the load of the vacuum pump of the final-stage vacuum chamber and facilitate the desolvation of analyte, thereby improving the detection sensitivity of the mass spectrometer.
The above embodiments illustrate the principle and functions of the present invention through examples simply and are not intended to limit the present invention. Those familiar with the technology may make modifications or changes to the above embodiments without departing from the spirit and scope of the present invention. Thus, all modifications or changes accomplished by the ordinary staff in this technical field without departing from the spirit and technical idea disclosed in the present invention are intended to be covered by the claims appended below.
Number | Date | Country | Kind |
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201510430131.8 | Jul 2015 | CN | national |
Filing Document | Filing Date | Country | Kind |
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PCT/IB2016/054330 | 7/21/2016 | WO | 00 |