CN110596401B - High-field asymmetric waveform ion mobility device and method for protein detection - Google Patents
High-field asymmetric waveform ion mobility device and method for protein detection Download PDFInfo
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Abstract
The invention discloses a high-field asymmetric waveform ion mobility device for protein detection, which is characterized in that: the device comprises an electrospray ion source, a first group of electrode plates, a second group of electrode plates, a mass spectrometer, a sine wave power supply, a high-field asymmetric waveform power supply and a direct current power supply, wherein a sample inlet is formed in one side of the first group of electrode plates, the first group of electrode plates and the second group of electrode plates are coaxially arranged in parallel front and back, a pre-annealing area is formed between the first group of electrode plates, a separation area is formed between the second group of electrode plates, the rear end of the second group of electrode plates is connected with the mass spectrometer, the first group of electrode plates are connected with the sine wave power supply and a temperature control module, the second group of electrode plates are connected with the high-field asymmetric waveform power supply and the direct current power supply, and protein sample ions generated by the electrospray ion source pass through the pre-annealing area and the separation area under the pushing of carrier gas. The invention is suitable for detecting complex structure molecules with stereoisomers and intermediates, especially protein detection, and has the advantages that: the resolution and sensitivity of the detection are improved, and the repeatability is good.
Description
Technical Field
The invention relates to the technical field of ion separation detection, in particular to a high-field asymmetric waveform ion mobility device and method for protein detection.
Background
High field asymmetric waveform ion mobility (FIELD ASYMMETRIC Ion Mobility Spectrometry, FAIMS) is a fast gas phase ion separation technique developed in the traditional ion mobility technology. The ion mobility of the high-field asymmetric waveform utilizes the characteristic that the periods of the high electric field and the low electric field are alternately changed, and different ions are separated in the pole plate gap according to the difference of ion mobility under the conditions of the high electric field and the low electric field. The technology has the advantages of simple structure, small core device, easy continuous detection and the like, has great development potential in the field of on-site analysis and detection, and is currently applied to separation and detection of partial protein isomers.
The existing high-field asymmetric waveform ion mobility device is generally composed of an ionization region, a separation region and a detection region, wherein a sample is ionized into sample ions in the ionization region and then is brought into the separation region by carrier gas, the separation region is used for separating target ions by applying high-field asymmetric waveform voltage, compensation voltage is applied for compensating high-field and low-field motion deviation of the target ions, and the target ions finally enter the detection region to be detected.
The technology still has the following defects when being used for detecting complex structure molecules such as protein and the like: (1) low resolution: because the protein has a complex structure and a plurality of isomers and also has the difference of three-dimensional space structures, the existing high-field asymmetric waveform ion mobility technology has insufficient resolution in protein analysis, and the space information is difficult to determine, so that the separation and identification of the stereoisomers at the complete protein level are realized; (2) low sensitivity: the existing high-field asymmetric waveform ion mobility technology can only pass ions with corresponding compensation voltage at the same time, and other ions are neutralized by the upper electrode plate and the lower electrode plate of the separation area, so that the ions detected by the subsequent detector are greatly reduced, and the sensitivity is affected; (3) poor repeatability: because the protein structure is easily affected by temperature, the too high temperature in the separation area during continuous operation can easily cause the protein to generate self-cleaning phenomenon during the separation process, namely, the signal can be seriously inhibited while eliminating the intermediate among more stable isomers, so that the repeatability of the sample detection is affected.
Disclosure of Invention
In order to solve the defects in the prior art, the invention provides a high-field asymmetric waveform ion mobility device and a high-field asymmetric waveform ion mobility method for protein detection, which can improve the resolution and sensitivity of protein detection and have good repeatability.
The technical scheme adopted for solving the technical problems is as follows: the utility model provides a high-field asymmetric waveform ion mobility device for protein detection, includes electrospray ion source, first group electrode plate, second group electrode plate, mass spectrometer, sine wave power, high-field asymmetric waveform power, direct current source and gas generator, one side of first group electrode plate be provided with the confession electrospray ion source ionization produce protein sample ion get into advance the entry, first group electrode plate with second group electrode plate around coaxial parallel arrangement, first group electrode plate with second group electrode plate between leave the clearance, first group electrode plate between constitute the preanneal region, second group electrode plate between constitute the separation zone, second group electrode plate rear end connect mass spectrometer's detection entry, first group electrode plate with sine wave power electricity be connected, the outside of first group electrode plate be provided with be used for controlling the temperature control module of preanneal region, second group and high-field asymmetric waveform power and the direct current source of gas generator of connection the ionization region after the sample of carrier gas generator through the preanneal region of the gas generator.
In some embodiments, the first group of electrode plates and the second group of electrode plates are formed by two plate-type electrode plates which are symmetrical up and down, and the electrode plate intervals of the first group of electrode plates and the second group of electrode plates are equal. Thus, the method has better protein ion pre-annealing and separating effects.
In some embodiments, the electrode plate spacing of the first set of electrode plates and the second set of electrode plates is 0.1mm to 10cm, preferably 1mm to 5mm. Therefore, the method has a better effect and is beneficial to improving the detection resolution.
In some embodiments, the sine wave power supply has a voltage amplitude of not less than 3kV. Therefore, the annealing reaction of protein sample ions in the pre-annealing area can be better realized, and the performance stability of the protein ions in the subsequent separation process is improved.
In some embodiments, the high-field asymmetric waveform power supply can use square waves, half sine waves or double sine waves, and the voltage amplitude of the high-field asymmetric waveform power supply is not less than 3kV, and the frequency is 1 kHz-100 MHz, preferably 100kHz. Thereby having better separation effect.
A method for detecting protein by adopting a high-field asymmetric waveform ion mobility device comprises the following steps:
① Ionizing a target protein sample in the solution by using an electrospray ion source to generate protein sample ions, wherein the protein sample ions enter a first group of electrode plates and are pushed to move forwards by carrier gas;
② Providing a sine wave power supply for the first group of electrode plates, providing a stable temperature field for a pre-annealing area of the first group of electrode plates through a temperature control module, and carrying out oscillation movement of protein sample ions in the pre-annealing area under the combined action of carrier gas, the sine wave power supply and the temperature field to finish pre-annealing;
③ Providing a high-field asymmetric waveform power supply and a direct current power supply for the second group of electrode plates, enabling protein sample ions to continuously move forwards to a separation area in the second group of electrode plates under the pushing of carrier gas, separating target protein ions in the separation area, and enabling the target protein ions to enter a mass spectrometer for detection to obtain a mass spectrum signal of scanning compensation voltage, and neutralizing other ions in the separation area;
④ Changing the compensation voltage of the direct current power supply, and repeating the step ①-③ to obtain mass spectrum signals under different compensation voltages;
⑤ And integrating mass spectrum signals under different compensation voltages to obtain a signal spectrogram of the high-field asymmetric waveform ion mobility of the target protein ions.
In some embodiments, the electrospray ion source generates protein sample ions including protein positive and negative ions and other ionizable particles. The electrospray ion source can ensure that the spatial structure of the generated protein sample ions is unchanged.
In some embodiments, the carrier gas is one of hydrogen, helium, nitrogen and sulfur hexafluoride, or a mixture of multiple of hydrogen, helium, nitrogen and sulfur hexafluoride according to any proportion, or a mixture of several of hydrogen, helium, nitrogen and sulfur hexafluoride and doping gas, wherein the doping gas is selected from ether, alcohol, ketone and aromatic hydrocarbon gases, and the flow rate of the carrier gas is 0.001L/min-30L/min, preferably 1L/min-5L/min. Therefore, the carrier gas adopts the mixture of a plurality of hydrogen, helium, nitrogen and sulfur hexafluoride and the doping gas, and the pre-annealing and separation effect can be further improved by combining a specific flow rate.
In some embodiments, the sine wave power supply in step ② has a voltage amplitude of not less than 3kV and the temperature field has a temperature range of 0 ℃ to 500 ℃, preferably 100 ℃ to 300 ℃. Therefore, a stable temperature field is provided for protein ion pre-annealing, the performance of protein ions after pre-annealing can be better achieved, the phenomenon of self-cleaning during subsequent separation is reduced, and the ion signal intensity is ensured.
In some embodiments, the compensation voltage of the DC power supply can be adjusted to be in a range of-200V to 200V.
Compared with the prior art, the invention has the advantages that:
(1) The protein sample ions are generated by arranging an electrospray ion source and sequentially pass through two groups of electrode plates under the pushing of carrier gas, the protein sample ions are oscillated to move under the action of a high-voltage sine wave power supply and a temperature field of a first group of electrode plates, collide with carrier gas molecules to convert heat energy, the temperature of the sample ions is increased to preheat, then the protein sample ions can be automatically maintained to a low-energy point state, an annealing effect is carried out in a pre-annealing area, the space structure and the performance of the protein are stabilized, the generation of a self-cleaning phenomenon of the protein can be reduced, and the uncontrollable self-cleaning phenomenon which occurs simultaneously in the original separation process is controlled, so that the subsequent separation effect is ensured, and the ion signal intensity is improved;
(2) The high-field asymmetric waveform power supply of the second group of electrode plates is used for separating protein sample ions, the direct-current power supply is used for compensating high-low field motion deviation of the sample ions among the second group of electrode plates, and finally target ions are separated and then enter a mass spectrometer for detection, compared with a traditional FAIMS structure, the space between the electrode plates can be increased from 1.9mm to 5mm, the separation time is increased from 0.2-0.4 s to 1-1.5 s, and the resolution can be greatly increased from 200-400 to about 800 on the premise of not losing the sensitivity, so that the accurate identification of the stereoisomers of the complete protein level is realized;
(3) The method can reasonably control the duration of protein ions in the pre-annealing stage and the separation stage, and the protein ions after the pre-annealing are not influenced by the excessive temperature during continuous operation, so that further isomerization is avoided, and the repeatability of a detection map is improved.
Drawings
FIG. 1 is a schematic diagram of a high field asymmetric waveform ion mobility device for protein detection according to the present invention.
The device comprises an electrospray ion source 1, a first group of electrode plates 2, a second group of electrode plates 3, a mass spectrometer 4, a sine wave power supply 5, a high-field asymmetric waveform power supply 6, a direct current power supply 7, a carrier gas 8, a sample inlet 9, a pre-annealing zone 10, a separation zone 11 and a temperature control module 12.
Detailed Description
The high field asymmetric waveform ion mobility apparatus and method for protein detection of the present invention is described in further detail below with reference to the accompanying drawings, but is not intended to limit the invention thereto.
Example 1
As shown in the figure, the high-field asymmetric waveform ion mobility device for protein detection comprises an electrospray ion source 1, a first group of electrode plates 2, a second group of electrode plates 3, a mass spectrometer 4, a sine wave power supply 5, a high-field asymmetric waveform power supply 6, a direct current power supply 7 and a gas generator, wherein one side of the first group of electrode plates 2 is provided with a sample inlet 9 for supplying protein sample ions generated by ionization of the electrospray ion source, the first group of electrode plates 2 and the second group of electrode plates 3 are coaxially arranged in parallel front and back, a gap is reserved between the first group of electrode plates 2 and the second group of electrode plates 3, a pre-annealing zone 10 is formed between the first group of electrode plates 2, a separation zone 11 is formed between the second group of electrode plates 3, the rear end of the second group of electrode plates 3 is connected with a detection inlet of the mass spectrometer 4, the first group of electrode plates 2 are electrically connected with the sine wave power supply 5, the outer side of the first group of electrode plates 2 is provided with a temperature control module 12 for controlling the temperature of the pre-annealing zone, the second group of electrode plates 3 is electrically connected with the high-field asymmetric waveform power supply 6 and the direct current power supply 7, and the gas generator is arranged at the front end of the first group of electrode plates 2, and the gas generator pushes the pre-annealing zone 8 to sequentially pass through the pre-annealing zone 10 and the pre-annealing zone 11 of protein ions generated by the pre-annealing zone.
In this embodiment, the upper electrode plate of the first group of electrode plates 2 is provided with the sample inlet 9, and the sample inlet direction of protein sample ions generated by ionization of the electrospray ion source forms a certain angle with the carrier gas direction, so that the loss of sample ions can be better reduced.
In this embodiment, the temperature control module 12 includes a heating plate closely disposed around the first set of electrode plates and a temperature sensor, where the heating plate is connected to an external power source, and the temperature sensor is connected to a control system for accurately controlling the temperature of the pre-annealing zone and ensuring a stable temperature field. The gas generator is also connected with a gas flow controller for controlling the carrier gas to maintain a steady flow rate.
In this embodiment, the first group electrode plate 2 and the second group electrode plate 3 are each composed of two plate electrode plates which are vertically symmetrical, the electrode plate pitches of the first group electrode plate 2 and the second group electrode plate 3 are equal and are both 4mm, in other embodiments, the electrode plate pitches may be 0.1mm, 1mm, 3mm, 5mm, 1cm, 10cm, etc.
In this embodiment, the voltage amplitude of the sine wave power supply 5 is not less than 3kV. The high-field asymmetric waveform power supply 6 is formed by superposition of double sine waves, wherein the waveform formed by superposition satisfies that the integral of one period is 0, that is, the integral area of the high-field part and the low-field part is the same, and in other embodiments, the high-field asymmetric waveform power supply 6 can achieve an approximate effect by adopting square waves, half sine waves or other high-order fitting waveforms. The voltage amplitude of the high-field asymmetric waveform power supply 6 is not less than 3kV, the frequency is 100kHz, and in other embodiments, the frequency of the high-field asymmetric waveform power supply 6 can be 1kHz, 10kHz, 500kHz, 10MHz, 100MHz, etc.
Mass to charge ratio (m/z) of the mass spectrometer 4 is in the range of 1 to 1000000amu, preferably 1000 to 200000amu, and mass resolution of the mass spectrometer 4 is in the range of 100 to 20000000. In this embodiment, the mass resolution of the mass spectrometer is not less than 10000 under the conditions of a mass-to-charge ratio of 1000amu and the highest sensitivity of the mass spectrometer, and the mass spectrometer has a better effect.
Example two
The invention discloses a method for detecting protein by adopting a high-field asymmetric waveform ion mobility device, which comprises the following steps:
① Using an electrospray ion source to ionize a target protein sample in the solution to generate protein sample ions, ensuring that the spatial structure of the protein sample ions is unchanged, and enabling the protein sample ions to enter a first group of electrode plates and move forwards by being pushed by carrier gas;
② Providing a sine wave power supply for the first group of electrode plates, providing a stable temperature field for a pre-annealing area of the first group of electrode plates through a temperature control module, and carrying out oscillation movement of protein sample ions in the pre-annealing area under the combined action of carrier gas, the sine wave power supply and the temperature field to finish pre-annealing;
③ Providing a high-field asymmetric waveform power supply and a direct current power supply for the second group of electrode plates, enabling protein sample ions to continuously move forwards to a separation area in the second group of electrode plates under the pushing of carrier gas, separating target protein ions in the separation area, and enabling the target protein ions to enter a mass spectrometer for detection to obtain a mass spectrum signal of scanning compensation voltage, and neutralizing other ions in the separation area;
④ Changing the compensation voltage of the direct current power supply, and repeating the step ①-③ to obtain mass spectrum signals under different compensation voltages;
⑤ And integrating mass spectrum signals under different compensation voltages to obtain a signal spectrogram of the high-field asymmetric waveform ion mobility of the target protein ions.
The protein sample ions generated by the electrospray ion source include protein positive and negative ions and other ionizable particles.
The carrier gas is one or more of hydrogen, helium, nitrogen and sulfur hexafluoride mixed according to any proportion, or a plurality of hydrogen, helium, nitrogen and sulfur hexafluoride mixed with doping gas, and the doping gas is selected from ether, alcohol, ketone and aromatic hydrocarbon gases, so that the separation effect of the target sample can be improved. The flow rate of the carrier gas is 0.001L/min to 30L/min, preferably 1L/min to 5L/min. In the step ②, the voltage amplitude of the sine wave power supply is not less than 3kV, and the temperature range of the temperature field is 0-500 ℃, preferably 100-300 ℃.
In the embodiment, the carrier gas is pure nitrogen or mixture of 75% nitrogen and 25% hydrogen, the flow rate is 2-3L/min, and the pre-annealing temperature is 100-150 ℃. The adjustable range of the compensation voltage of the direct current power supply is-200V. Based on the specific carrier gas flow rate, the pre-annealing temperature and the sine wave voltage, the protein is pre-annealed before separation, the uncontrollable self-cleaning phenomenon which occurs simultaneously in the original separation process is controlled, and the signal intensity of protein detection is ensured.
The invention relates to a high-field asymmetric waveform ion mobility device and a method for protein detection, and the basic working principle is as follows: after the protein sample ions are ionized by the electrospray ion source 1 to form sample ions, the sample ions sequentially pass through two groups of flat plate electrode plates under the pushing of carrier gas, the sample ions are subjected to the action of a temperature field stabilized by a high-voltage sine wave power supply 5 and a temperature control module 12 between the first group of electrode plates 2 (a pre-annealing area 10), the sample ions vibrate and collide with carrier gas molecules, part of kinetic energy is converted into heat energy, the temperature of the sample ions is increased to be preheated, and then the protein sample ions can be automatically maintained to a low-energy state to perform annealing action. The process can reduce the generation of the self-cleaning phenomenon of the protein, is beneficial to stabilizing the spatial structure and performance of the protein, is beneficial to subsequent separation, and improves the ion signal intensity. The protein sample ions are then separated between the second set of electrode plates 3 (separation region 11) by the action of the high field asymmetric waveform power supply 6, the target ions fly out of the separation region by the compensation of the dc power supply 7 and are finally detected by the mass spectrometer 4, while the remaining ions impinge on the electrode plates and are neutralised.
Based on the characteristics, the high-field asymmetric waveform ion mobility device and the method for protein detection, disclosed by the invention, lead in a protein pre-annealing stage, adopt sine waves with higher average voltage to pre-anneal the protein before separation, are beneficial to stabilizing the spatial structure and performance of the protein, can reduce the generation of the phenomenon of self-cleaning of the protein, and can control the phenomenon of uncontrollable self-cleaning which occurs simultaneously in the original separation process, thereby ensuring the subsequent separation effect and improving the ion signal intensity; compared with the traditional FAIMS structure, the electrode plate spacing of the invention can be increased from 1.9mm to 5mm, the separation time is increased from 0.2 to 0.4s to 1 to 1.5s, the residence time of ions in a separation area is prolonged, and the resolution can be greatly increased from 200 to 400 to about 800 on the premise of not losing the sensitivity, thus realizing the accurate identification of the stereoisomers at the complete protein level; the length of the electrode plate and the flow rate of the carrier gas can be used for reasonably controlling the duration of protein ions in the pre-annealing stage and the separation stage, and the protein ions after the pre-annealing are not influenced by the excessive temperature during continuous operation, so that further isomerization can be avoided, and the repeatability of a detection map is improved.
The high-field asymmetric waveform ion mobility device and method for protein detection are also suitable for detecting other molecules with complex structures and stereoisomers and intermediates.
It should be noted that the foregoing description is only a preferred embodiment of the present invention, and is not intended to limit the scope of the invention, and the present invention may also be modified by material and structure of the above-mentioned various components or by substitution of technical equivalents. Therefore, all equivalent structural changes made in the specification and the illustrated content of the present invention, or direct or indirect application to other related technical fields are included in the scope of the present invention.
Claims (9)
1. The high-field asymmetric waveform ion mobility device for protein detection is characterized by comprising an electrospray ion source, a first group of electrode plates, a second group of electrode plates, a mass spectrometer, a sine wave power supply, a high-field asymmetric waveform power supply, a direct current power supply and a gas generator, wherein the first group of electrode plates and the second group of electrode plates are composed of two flat plate electrode plates which are symmetrical up and down, the electrode plate intervals of the first group of electrode plates and the electrode plate interval of the second group of electrode plates are equal, one side of the first group of electrode plates is provided with a sample inlet for protein sample ions generated by ionization of the electrospray ion source to enter, the first group of electrode plates and the second group of electrode plates are coaxially arranged in parallel front and back, a gap is reserved between the first group of electrode plates and the second group of electrode plates, a pre-annealing area is formed between the first group of electrode plates, the separation area is formed between the second group of electrode plates, the rear end of the second group of electrode plates is connected with the detection inlet of the mass spectrometer, the first group of electrode plates are electrically connected with the sine wave power supply, the outer side of the first group of electrode plates is provided with a temperature control module for controlling the temperature of the pre-annealing area, the second group of electrode plates are electrically connected with the high-field asymmetric waveform power supply and the direct current power supply, the gas generator is arranged at the front end of the first group of electrode plates, the generated carrier gas pushes ionized protein sample ions to sequentially pass through the pre-annealing area and the separation area, the protein sample ions vibrate under the action of the high-voltage sine wave power supply and the temperature field of which the voltage amplitude of the first group of electrode plates is not less than 3kV and collide with carrier gas molecules to convert heat energy, the temperature of the sample ions is increased to preheat, then the protein sample ions are automatically maintained to a low-energy potential point state, and annealing is carried out in a pre-annealing area, so that the spatial structure and the performance of the protein are stabilized.
2. The high field asymmetric waveform ion mobility apparatus for protein detection as defined in claim 1, wherein the electrode plate spacing between the first set of electrode plates and the second set of electrode plates is 0.1mm to 10cm.
3. The high-field asymmetric waveform ion mobility device for protein detection according to claim 1, wherein the high-field asymmetric waveform power source can adopt square waves, half sine waves or double sine waves, and the voltage amplitude of the high-field asymmetric waveform power source is not less than 3kV, and the frequency is 1 kHz-100 MHz.
4. A method for protein detection using the high field asymmetric waveform ion mobility device of claim 1, comprising the steps of:
① Ionizing a target protein sample in the solution by using an electrospray ion source to generate protein sample ions, wherein the protein sample ions enter a first group of electrode plates and are pushed to move forwards by carrier gas;
② Providing a sine wave power supply for the first group of electrode plates, providing a stable temperature field for a pre-annealing area of the first group of electrode plates through a temperature control module, and carrying out oscillation movement of protein sample ions in the pre-annealing area under the combined action of carrier gas, the sine wave power supply and the temperature field to finish pre-annealing;
③ Providing a high-field asymmetric waveform power supply and a direct current power supply for the second group of electrode plates, enabling protein sample ions to continuously move forwards to a separation area in the second group of electrode plates under the pushing of carrier gas, separating target protein ions in the separation area, and enabling the target protein ions to enter a mass spectrometer for detection to obtain a mass spectrum signal of scanning compensation voltage, and neutralizing other ions in the separation area;
④ Changing the compensation voltage of the direct current power supply, and repeating the step ①-③ to obtain mass spectrum signals under different compensation voltages;
⑤ And integrating mass spectrum signals under different compensation voltages to obtain a signal spectrogram of the high-field asymmetric waveform ion mobility of the target protein ions.
5. The method of claim 4, wherein the electrospray ion source generates protein sample ions comprising positive and negative protein ions.
6. The method for detecting protein according to claim 4, wherein the carrier gas is one of hydrogen, helium, nitrogen and sulfur hexafluoride, or a mixture of a plurality of hydrogen, helium, nitrogen and sulfur hexafluoride in any proportion, or a mixture of a plurality of hydrogen, helium, nitrogen and sulfur hexafluoride with a doping gas selected from ethers, alcohols, ketones and aromatic hydrocarbon gases.
7. The method for protein detection according to claim 6, wherein the carrier gas has a flow rate of 0.001L/min to 30L/min.
8. The method for protein detection according to claim 4, wherein the sine wave power supply in step ② has a voltage amplitude of not less than 3kV and the temperature field has a temperature range of 0 ℃ to 500 ℃.
9. The method for protein detection according to claim 4, wherein the compensation voltage of the DC power supply is adjustable within a range of-200V to 200V.
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Citations (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6639212B1 (en) * | 1998-08-05 | 2003-10-28 | National Research Council Canada | Method for separation of isomers and different conformations of ions in gaseous phase |
| WO2004090534A1 (en) * | 2003-04-01 | 2004-10-21 | The Charles Stark Draper Laboratory, Inc. | Non-invasive breath analysis using field asymmetric ion mobility spectrometry |
| CN1585666A (en) * | 2001-04-17 | 2005-02-23 | 查尔斯斯塔克布料实验室公司 | Methods and apparatus for electrospray-augmented high field asymmetric ion mobility spectrometry |
| CN101571508A (en) * | 2009-06-16 | 2009-11-04 | 清华大学 | High-field asymmetric waveform ion mobility spectrometer with multi-layer plate structure |
| CN103854954A (en) * | 2012-12-06 | 2014-06-11 | 中国科学院大连化学物理研究所 | Thermal desorption membrane inlet high field asymmetry waveform ion migration spectrometer |
| CN107064517A (en) * | 2016-01-14 | 2017-08-18 | 萨默费尼根有限公司 | The method based on mass spectrographic sign for biomolecule |
| CN107635477A (en) * | 2015-03-06 | 2018-01-26 | 英国质谱公司 | For being coupled to rapid evaporation MALDI-MS（“REIMS”）The entrance instrument of the ion analyser of device |
| CN108091542A (en) * | 2016-11-23 | 2018-05-29 | 中国科学院大连化学物理研究所 | A kind of effectively ionized method of High-Field Asymmetric Waveform Ion Mobility Spectrometer sample |
| CN108717927A (en) * | 2018-05-23 | 2018-10-30 | 宁波盘福生物科技有限公司 | Multichannel glow discharge Penning ion source device |
| CN109065435A (en) * | 2018-08-28 | 2018-12-21 | 山东省分析测试中心 | A kind of micro- ionization spray ion source difference ion mobility spectrometry and its application method |
| CN109326525A (en) * | 2018-08-20 | 2019-02-12 | 西安电子科技大学 | Mixed polarity AlGaN/GaN high electron mobility transistor based on sputtered AlN substrate and preparation method thereof |
| CN109682906A (en) * | 2019-01-10 | 2019-04-26 | 宁波大学 | A kind of gas-chromatography-low temperature plasma ion-source mass spectrometer combined apparatus |
| CN109863391A (en) * | 2016-10-05 | 2019-06-07 | 雅培实验室 | Device and method for sample analysis |
| CN110186990A (en) * | 2018-02-23 | 2019-08-30 | 布鲁克科学有限公司 | Series connection ionic migration spectrometer |
| CN211148673U (en) * | 2019-09-11 | 2020-07-31 | 宁波盘福生物科技有限公司 | High-field asymmetric waveform ion mobility device for protein detection |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8299443B1 (en) * | 2011-04-14 | 2012-10-30 | Battelle Memorial Institute | Microchip and wedge ion funnels and planar ion beam analyzers using same |
| US9926596B2 (en) * | 2011-05-27 | 2018-03-27 | Genapsys, Inc. | Systems and methods for genetic and biological analysis |
| US9089279B2 (en) * | 2011-12-29 | 2015-07-28 | General Electric Company | Ion-based breath analysis system |
| US10386372B1 (en) * | 2018-02-09 | 2019-08-20 | The Florida International University Board Of Trustees | Materials and methods for screening topoisomers |
-
2019
- 2019-09-11 CN CN201910858501.6A patent/CN110596401B/en active Active
Patent Citations (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6639212B1 (en) * | 1998-08-05 | 2003-10-28 | National Research Council Canada | Method for separation of isomers and different conformations of ions in gaseous phase |
| CN1585666A (en) * | 2001-04-17 | 2005-02-23 | 查尔斯斯塔克布料实验室公司 | Methods and apparatus for electrospray-augmented high field asymmetric ion mobility spectrometry |
| WO2004090534A1 (en) * | 2003-04-01 | 2004-10-21 | The Charles Stark Draper Laboratory, Inc. | Non-invasive breath analysis using field asymmetric ion mobility spectrometry |
| CN101571508A (en) * | 2009-06-16 | 2009-11-04 | 清华大学 | High-field asymmetric waveform ion mobility spectrometer with multi-layer plate structure |
| CN103854954A (en) * | 2012-12-06 | 2014-06-11 | 中国科学院大连化学物理研究所 | Thermal desorption membrane inlet high field asymmetry waveform ion migration spectrometer |
| CN107635477A (en) * | 2015-03-06 | 2018-01-26 | 英国质谱公司 | For being coupled to rapid evaporation MALDI-MS（“REIMS”）The entrance instrument of the ion analyser of device |
| CN107064517A (en) * | 2016-01-14 | 2017-08-18 | 萨默费尼根有限公司 | The method based on mass spectrographic sign for biomolecule |
| CN109863391A (en) * | 2016-10-05 | 2019-06-07 | 雅培实验室 | Device and method for sample analysis |
| CN108091542A (en) * | 2016-11-23 | 2018-05-29 | 中国科学院大连化学物理研究所 | A kind of effectively ionized method of High-Field Asymmetric Waveform Ion Mobility Spectrometer sample |
| CN110186990A (en) * | 2018-02-23 | 2019-08-30 | 布鲁克科学有限公司 | Series connection ionic migration spectrometer |
| CN108717927A (en) * | 2018-05-23 | 2018-10-30 | 宁波盘福生物科技有限公司 | Multichannel glow discharge Penning ion source device |
| CN109326525A (en) * | 2018-08-20 | 2019-02-12 | 西安电子科技大学 | Mixed polarity AlGaN/GaN high electron mobility transistor based on sputtered AlN substrate and preparation method thereof |
| CN109065435A (en) * | 2018-08-28 | 2018-12-21 | 山东省分析测试中心 | A kind of micro- ionization spray ion source difference ion mobility spectrometry and its application method |
| CN109682906A (en) * | 2019-01-10 | 2019-04-26 | 宁波大学 | A kind of gas-chromatography-low temperature plasma ion-source mass spectrometer combined apparatus |
| CN211148673U (en) * | 2019-09-11 | 2020-07-31 | 宁波盘福生物科技有限公司 | High-field asymmetric waveform ion mobility device for protein detection |
Non-Patent Citations (4)
| Title |
|---|
| Distortion of Ion Structures by Field Asymmetric Waveform Ion Mobility Spectrometry;Alexandre A. Shvartsburg 等;Anal. Chem.;20070118;第79卷(第4期);1523–1528 * |
| To What Extent is FAIMS Beneficial in the Analysis of Proteins?;Helen J. Cooper;J. Am. Soc. Mass Spectrom.;20161231;第27卷(第4期);566–577 * |
| 基于FAIMS谱图峰位置的离子迁移率非线性函数解析;王电令;陈池来;赵聪;高钧;孔德义;尤晖;Juergen Brugger;;光谱学与光谱分析;20120815(第08期);2050-2055 * |
| 蛋白质的微芯片电泳分离及其与脱氧核糖核酸迁移规律的比较;刘春叶 等;色谱;20101231;第28卷(第03期);296-300 * |
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