WO2023193481A1 - 一种用于质谱分析的微孔震荡雾化电喷雾萃取电离装置 - Google Patents
一种用于质谱分析的微孔震荡雾化电喷雾萃取电离装置 Download PDFInfo
- Publication number
- WO2023193481A1 WO2023193481A1 PCT/CN2022/141856 CN2022141856W WO2023193481A1 WO 2023193481 A1 WO2023193481 A1 WO 2023193481A1 CN 2022141856 W CN2022141856 W CN 2022141856W WO 2023193481 A1 WO2023193481 A1 WO 2023193481A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- polar solvent
- electrospray
- capillary
- micropore
- spray
- Prior art date
Links
- 238000000889 atomisation Methods 0.000 title claims abstract description 35
- 230000010355 oscillation Effects 0.000 title claims abstract description 8
- 238000000132 electrospray ionisation Methods 0.000 title abstract description 4
- 238000001819 mass spectrum Methods 0.000 title abstract 2
- 239000002904 solvent Substances 0.000 claims abstract description 59
- 239000002798 polar solvent Substances 0.000 claims description 201
- 239000007921 spray Substances 0.000 claims description 145
- 238000000605 extraction Methods 0.000 claims description 124
- 239000000523 sample Substances 0.000 claims description 72
- 238000004949 mass spectrometry Methods 0.000 claims description 36
- 239000012488 sample solution Substances 0.000 claims description 36
- 238000002347 injection Methods 0.000 claims description 28
- 239000007924 injection Substances 0.000 claims description 28
- 230000005540 biological transmission Effects 0.000 claims description 26
- 239000002184 metal Substances 0.000 claims description 26
- 238000012546 transfer Methods 0.000 claims description 14
- 238000000520 microinjection Methods 0.000 claims description 8
- 238000010146 3D printing Methods 0.000 claims description 5
- 230000008878 coupling Effects 0.000 claims 6
- 238000010168 coupling process Methods 0.000 claims 6
- 238000005859 coupling reaction Methods 0.000 claims 6
- 238000005507 spraying Methods 0.000 abstract 2
- 239000000126 substance Substances 0.000 description 35
- 239000000243 solution Substances 0.000 description 30
- 210000004027 cell Anatomy 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 11
- 230000009471 action Effects 0.000 description 10
- 239000000284 extract Substances 0.000 description 8
- 230000003834 intracellular effect Effects 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 210000000170 cell membrane Anatomy 0.000 description 4
- 210000003463 organelle Anatomy 0.000 description 4
- 239000012491 analyte Substances 0.000 description 3
- 230000005611 electricity Effects 0.000 description 3
- 239000011148 porous material Substances 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 230000005684 electric field Effects 0.000 description 2
- 238000007787 electrohydrodynamic spraying Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 239000012080 ambient air Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000005672 electromagnetic field Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000000752 ionisation method Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 238000006276 transfer reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/02—Details
- H01J49/10—Ion sources; Ion guns
- H01J49/16—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
- H01J49/165—Electrospray ionisation
- H01J49/167—Capillaries and nozzles specially adapted therefor
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/26—Mass spectrometers or separator tubes
Definitions
- the present application relates to the technical field of mass spectrometry analysis, and in particular to a micropore vibration atomization electrospray extraction ionization device for mass spectrometry analysis.
- a mass spectrometer is an instrument that separates and analyzes charged ions under the action of an electromagnetic field. It mainly includes several parts such as an ionization source, a mass analyzer, and a detector.
- the ionization source ionizes the substance to be measured into a charged state, which is the first and critical step in mass spectrometry analysis. Therefore, the ionization source is called the heart of the mass spectrometer.
- the electrospray ionization source is the most common and widely used ionization source.
- the sample solution containing the substance to be measured flows through the capillary tube, and a high DC voltage is applied at the outlet of the capillary tube.
- the capillary tube is coaxially equipped with heated atomization gas.
- solvent molecules will spray at the capillary outlet and atomize into micron-sized charged droplets.
- solvent evaporation and Coulomb explosion the substance to be measured will eventually turn into gaseous ions and enter the mass spectrometer. The instrument is analyzed.
- electrospray extraction ionization an electrospray extraction ionization device composed of two crossed electrosprays.
- one electrospray is the sample solution
- the other electrospray is the extraction ionization solvent. Extraction and charge transfer occur at the intersection of the two electrosprays to achieve extraction ionization of the substance to be measured, and then enter the mass spectrometer for analysis.
- the sample solution ionized by electrospray extraction is not directly electrosprayed into the mass spectrometer, but is extracted and charge transferred with another electrospray of pure solvent to achieve ionization of the substance to be measured.
- This technical method reduces the amount of water in the sample solution. There is interference from the ionization of the analyte such as the matrix. Extraction solvents of different polarities have better extraction effects on analyte molecules with different polarities.
- electrospray extraction ionization is an extraction ionization process that occurs in an open environment with the cross-collision of electrosprays assisted by two beams of atomizing gas.
- electrospray extraction ionization is an extraction ionization process that occurs in an open environment with the cross-collision of electrosprays assisted by two beams of atomizing gas.
- the extraction solvent is single and cannot achieve simultaneous analysis of polar substances and weakly polar substances;
- Both the sample solution and the extraction solvent are electrosprays assisted by atomizing gas, which rely on gas cylinders or serial gas lines, making it impossible to achieve portable integration and movement of the ionization source device, and the gas usage cost is high;
- the direction of the high-speed airflow of the two electrospray beams is inconsistent with the direction of the entrance of the mass spectrometer, which will affect the transmission efficiency of the substance to be measured to the entrance of the mass spectrometer, causing signal loss.
- this application provides a micropore oscillating atomization electrospray extraction ionization device for mass spectrometry analysis.
- the droplet collision and extraction ionization occur in the extraction ionization chamber, and it also makes the sample spray device and solvent electrospray
- the spray angle of the device and the spatial position between it and the mass spectrometer inlet are fixed, which helps to improve the stability and repeatability of electrospray extraction ionization.
- a micropore oscillating atomization electrospray extraction ionization device for mass spectrometry analysis including a sample spray device, a solvent electrospray device and an extraction ionization chamber;
- the extraction ionization chamber is provided with a sample spray droplet inlet, a solvent spray droplet inlet and an outlet respectively; the extension line of the sample spray droplet inlet to the inner cavity of the extraction ionization chamber is connected to the solvent spray droplet inlet.
- the extension lines to the inner cavity of the extraction ionization chamber intersect;
- the sample spray droplet inlet of the extraction ionization chamber is connected to the outlet of the sample spray device, the solvent spray droplet inlet is connected to the outlet of the solvent electrospray device, and the outlet is used to connect to the inlet of the mass spectrometer.
- the sample spray device includes:
- a high-frequency microporous vibrating plate is provided at the sample spray droplet inlet of the extraction ionization chamber and used for injecting or dropping samples.
- the sample spray droplet inlet is opened at the top of the extraction ionization chamber, and the solvent spray droplet inlet is opened at the side wall of the extraction ionization chamber.
- the sample spray device further includes a sample solution syringe pump and a sample solution transfer capillary;
- the inlet end of the sample solution transmission capillary is connected to the outlet end of the sample solution syringe pump, and the outlet end is used to align the high-frequency micropore oscillating plate.
- the solvent spray droplet inlet includes a polar solvent spray droplet inlet and a weakly polar solvent spray droplet inlet;
- the solvent electrospray device includes a polar solvent electrospray device and a weakly polar solvent electrospray device; the outlet of the polar solvent electrospray device is connected to the polar solvent spray droplet inlet, and the weakly polar solvent The outlet of the electrospray device is connected to the inlet of the weakly polar solvent spray droplets.
- the polar solvent electrospray device includes a polar solvent spray body
- the weakly polar solvent electrospray device includes a weakly polar solvent spray body
- the solvent electrospray device also includes a DC high-voltage power supply and a high-frequency switch;
- the DC high-voltage power supply is communicatively connected to the high-frequency switch, and the high-frequency switch is electrically connected to the capillary tube of the polar solvent spray body and the capillary tube of the weakly polar solvent spray body respectively.
- the polar solvent spray body includes a polar solvent injection pump and a polar solvent capillary; the inlet end of the polar solvent capillary is connected to the outlet end of the polar solvent injection pump, and the outlet end is connected to the polar solvent capillary tube.
- the solvent spray droplet inlet is connected and electrically connected to the high-frequency switch;
- the weakly polar solvent spray body includes a weakly polar solvent injection pump and a weakly polar solvent capillary; the inlet end of the weakly polar solvent capillary is connected to the outlet end of the weakly polar solvent injection pump, and the outlet end is connected to the weakly polar solvent injection pump.
- the weakly polar solvent spray droplet inlet is connected and electrically connected to the high-frequency switch.
- the polar solvent spray body further includes a polar solvent metal two-way;
- the polar solvent metal two-way is connected to the middle part of the polar solvent capillary tube and is electrically connected to the high-frequency switch;
- the weakly polar solvent spray body also includes a weakly polar solvent metal two-way; the weakly polar solvent metal two-way is connected to the middle part of the weakly polar solvent capillary and is electrically connected to the high-frequency switch. connect.
- the polar solvent spray droplet inlet and the weakly polar solvent spray droplet inlet are opened on the same side wall of the extraction ionization chamber, and the outlet is opened on another side of the extraction ionization chamber.
- the outlet end of the polar solvent capillary tube is inclined downward in the horizontal direction and is connected to the polar solvent spray droplet inlet, and the outlet end of the weak polar solvent capillary tube is inclined upward in the horizontal direction and is connected to the weak polar solvent spray port.
- the droplet inlets are connected.
- the extraction ionization chamber is made by 3D printing.
- Figure 1 is a schematic structural diagram of a micropore vibration atomization electrospray extraction ionization device for mass spectrometry analysis provided by an embodiment of the present application;
- Figure 2 is a flow chart of a micropore vibration atomization electrospray extraction ionization device for mass spectrometry analysis provided in an embodiment of the present application.
- 1 is a high-frequency microporous oscillating plate
- 2 is an extraction ionization chamber
- 3 is a sample solution syringe pump
- 4 is a sample solution transmission capillary
- 5 is a polar solvent syringe pump
- 6 is a polar solvent transmission capillary
- 7 It is a metal coupler for polar solvent
- 8 is a polar electrospray capillary
- 9 is a weakly polar solvent syringe pump
- 10 is a weakly polar solvent transmission capillary
- 11 is a metal coupler for weakly polar solvent
- 12 is a weakly polar electrospray capillary.
- Spray capillary, 13 is a DC high-voltage power supply
- 14 is a high-frequency switch
- 15 is a mass spectrometer inlet transmission capillary
- 16 is a mass spectrometer.
- the micropore oscillating atomization electrospray extraction ionization device for mass spectrometry analysis includes a sample spray device, a solvent electrospray device and an extraction ionization chamber (2);
- the extraction ionization chamber 2 is provided with a sample spray droplet inlet, a solvent spray droplet inlet and an outlet respectively; the sample spray droplet inlet is an extension line to the inner cavity of the extraction ionization chamber 2, and the solvent spray droplet inlet is to the extraction ionization chamber. 2 The extension lines of the inner cavity intersect;
- the sample spray droplet inlet of the extraction ionization chamber 2 is connected to the outlet of the sample spray device, the solvent spray droplet inlet is connected to the outlet of the solvent electrospray device, and the outlet is used to connect to the inlet of the mass spectrometer 16 .
- the inner extension line of the sample spray droplet inlet intersects with the inner extension line of the solvent spray droplet inlet, so that the spray droplets of the sample spray device and the solvent electrospray device are in the extraction ionization chamber 2
- An intersection point is formed in the extraction ionization chamber 2, thereby causing the spray droplets of the two paths to collide, extract and transfer charge in the extraction ionization chamber 2, extracting the substance to be measured in the ionized sample, and then under the vacuum negative pressure of the mass spectrometer 16,
- the substance to be measured extracted and ionized in the extraction ionization chamber 2 is transferred to the mass spectrometer 16 for mass spectrometry analysis.
- the electrospray extraction ionization of this scheme occurs in the extraction ionization chamber 2, which can avoid being affected by external factors such as ambient air flow, and the angle of the two spray droplets and the spatial position between the entrance of the mass spectrometer 16 are all fixed, thus helping to improve the stability and repeatability of electrospray extraction ionization.
- the sample spray device includes:
- a high-frequency micropore oscillating plate 1 is provided at the sample spray droplet inlet of the extraction ionization chamber 2 and is used to inject or drop the sample.
- a sample is applied to the high-frequency microporous oscillating plate 1.
- the sample quickly passes through the microporous plate of the high-frequency microporous oscillating plate 1 and is broken into micron-sized droplet sprays. Then enter the extraction ionization chamber 2.
- this solution uses a high-frequency microporous vibrator 1 as the sample spray device to atomize the sample into a micron-sized droplet plume. It is not only suitable for continuously flowing solution samples, but also for droplet samples, cell samples, etc.
- the cell membrane, organelles, etc. are fragmented and cut by micron-sized pores, and intracellular substances are completely released into the sample droplets, enabling complete and efficient analysis of cellular substances.
- the sample spray droplet inlet is opened at the top of the extraction ionization chamber 2
- the solvent spray droplet inlet is opened at the side wall of the extraction ionization chamber 2 .
- This solution is designed so that the sample spray droplets can naturally fall vertically into the extraction ionization chamber 2 .
- the bottom end of the high-frequency microporous vibrating plate 1 is connected to the top end of the extraction ionization chamber 2.
- the sample spray device also includes a sample solution syringe pump 3 and a sample solution transmission capillary 4;
- the inlet end of the sample solution transmission capillary 4 is connected to the outlet end of the sample solution syringe pump 3.
- the sample solution syringe pump 3 is a stepper motor micro-injection pump, and is equipped with a 1mL syringe to set the flow rate of the sample solution.
- the syringe The sample solution is pre-extracted by driving the stepper motor micro-injection pump, and then the outlet end of the syringe is connected to the inlet end of the sample solution transmission capillary 4 to transport the sample solution; the outlet end of the sample solution transmission capillary 4 is used to align the high
- the high-frequency microporous oscillating plate 1, that is, the outlet end of the sample solution transmission capillary 4 and the microporous plate of the high-frequency microporous oscillating plate 1 form an alignment fit.
- This solution is designed in such a way to facilitate the automatic injection of the sample solution into the high-frequency microporous oscillating plate 1, and also uses a sample solution injection pump 3 without atomization gas assistance to provide power for sample solution transmission, that is, the sample spray device is
- the sample spray device without nebulizer gas assistance helps to get rid of the restrictions of using cylinder gas, reduces the cost of use, and makes the device easy to be portable, integrated and moved.
- the solvent spray droplet inlet includes a polar solvent spray droplet inlet and a weakly polar solvent spray droplet inlet;
- the solvent electrospray device includes a polar solvent electrospray device and a weakly polar solvent electrospray device; the outlet of the polar solvent electrospray device is connected to the polar solvent spray droplet inlet, and the outlet of the weakly polar solvent electrospray device is connected to the described
- the weakly polar solvent spray droplets are connected to the inlet.
- This solution is designed in such a way that on the one hand, the polar solvent electrospray device generates polar solvent electrospray under the action of high DC voltage, and interacts with the sample spray droplets in the extraction ionization chamber 2, and extracts the ionized sample droplets.
- the substance to be measured is of medium polarity; on the other hand, the weakly polar solvent electrospray device generates weakly polar solvent electrospray under the action of DC high voltage, and interacts with the sample spray droplets in the extraction ionization chamber 2, and Extract the weakly polar analyte in the ionized sample droplets.
- this solution uses two solvent electrospray devices of different polarities to extract polar and weakly polar substances in the ionized sample droplets, maximizing the realization of the separation of polar and weakly polar substances. Simultaneous ionization analysis.
- the polar solvent electrospray device includes a polar solvent spray body
- the weakly polar solvent electrospray device includes a weakly polar solvent spray body
- the solvent electrospray device also includes a DC high-voltage power supply 13 and a high-frequency switch 14;
- the DC high-voltage power supply 13 is communicatively connected to the high-frequency switch 14, and the high-frequency switch 14 is electrically connected to the capillary tube of the polar solvent spray body and the capillary tube of the weakly polar solvent spray body respectively.
- This solution is designed in such a way that the high-voltage electricity provided by the DC high-voltage power supply 13 is switched and output to the capillary tubes of the polar solvent spray body and the weakly polar solvent spray body through the high-frequency switch 14 to achieve polarity and weak polarity.
- the alternation of solvent electrospray occurs, thereby facilitating the separate extraction of polar and weakly polar substances in the ionized sample droplets.
- this solution uses dual-solvent electrospray devices of different polarities to facilitate alternating electrospraying of polar and weakly polar solvents, and to facilitate the extraction of polar and weakly polar substances in the ionized sample droplets, thereby maximizing the Simultaneous ionization analysis of multiple substances is achieved to the maximum extent possible.
- the polar solvent electrospray device and the weakly polar solvent electrospray device of this solution share a DC high-voltage power supply 13.
- the polar solvent spray body includes a polar solvent injection pump 5 and a polar solvent capillary; the inlet end of the polar solvent capillary is connected to the outlet end of the polar solvent injection pump 5.
- polar solvent injection pump 5 and a polar solvent capillary tube are connected.
- the sexual solvent syringe pump 5 is a stepper motor micro-injection pump. It is equipped with a 1mL syringe and can set the polar solvent flow rate.
- the syringe is driven by the stepper motor micro-injection pump to pre-extract the polar solvent, and then the outlet of the syringe is The end is connected to the inlet end of the polar solvent capillary tube to transport the polar solvent; the outlet end of the polar solvent capillary tube is connected to the polar solvent spray droplet inlet, and is electrically connected to the high-frequency switch 14;
- the main body of the weakly polar solvent spray includes a weakly polar solvent injection pump 9 and a weakly polar solvent capillary; the inlet end of the weakly polar solvent capillary is connected to the outlet end of the weakly polar solvent injection pump 9.
- the weakly polar solvent injection Pump 9 is a stepper motor micro-injection pump, equipped with a 1mL syringe, which can set the flow rate of weakly polar solvents.
- the syringe is driven by the stepper motor microinjection pump to pre-extract the weakly polar solvent, and then the outlet end of the syringe is
- the inlet end of the weakly polar solvent capillary is connected to transport the weakly polar solvent; the outlet end of the weakly polar solvent capillary is connected with the weakly polar solvent spray droplet inlet, and is electrically connected to the high-frequency switch 14 .
- This solution is designed so that both solvent spray bodies use solvent injection pumps without atomizing gas assistance to provide power for electrospray solvent transmission, that is, both solvent electrospray devices use solvents without atomizing gas assistance.
- the electrospray device thus helps to get rid of the limitations of using cylinder gas, reduces the cost of use, and makes the device easy to be portable, integrated and moved.
- the polar solvent spray body also includes a polar solvent metal two-way connection 7;
- the polar solvent metal two-way connection 7 is connected to the middle part of the polar solvent capillary tube and is electrically connected to the high-frequency switch 14;
- the main body of the weakly polar solvent spray also includes a weakly polar solvent metal two-way pass 11; the weakly polar solvent metal two-way pass 11 is connected to the middle part of the weakly polar solvent capillary tube and is electrically connected to the high-frequency switch 14.
- This solution is designed in such a way that the capillaries of the two solvent spray bodies are connected to the DC high voltage.
- the weakly polar solvent capillary includes a polar solvent transfer capillary 6 and a polar electrospray capillary 8; in this application, the inlet end of the polar solvent transfer capillary 6 and the outlet end of the polar solvent injection pump 5 Connected, the outlet end is connected to one end of the polar solvent metal two-way 7; the inlet end of the polar electrospray capillary 8 is connected to the other end of the polar solvent metal two-way 7, and the outlet end is connected to the polar solvent spray droplet inlet;
- the weakly polar solvent capillary includes a weakly polar solvent transfer capillary 10 and a weakly polar electrospray capillary 12; in this application, the inlet end of the weakly polar solvent transfer capillary 10 is connected to the outlet end of the weakly polar solvent injection pump 9, The outlet end is connected to one end of the weakly polar solvent metal two-way 11; the inlet end of the weakly polar electrosp
- the polar solvent spray droplet inlet and the weak polar solvent spray droplet inlet are opened on the same side wall of the extraction ionization chamber 2, and the outlet is opened on the other side of the extraction ionization chamber 2.
- the side walls are respectively arranged opposite to the polar solvent spray droplet inlet and the weakly polar solvent spray droplet inlet;
- the outlet end of the polar solvent capillary is inclined downward in the horizontal direction and is connected to the polar solvent spray droplet inlet, and the outlet end of the weakly polar solvent capillary is inclined upward in the horizontal direction and is connected to the weakly polar solvent spray droplet inlet. That is to say, the polar and weakly polar solvent electrosprays in this scheme are introduced from the side wall of the extraction ionization chamber 2 at a certain angle in the horizontal direction, and interact with the vertically falling sample spray droplets in the extraction ionization chamber 2 Interactive collisions occur, and the ionized polar and weakly polar test substances are extracted respectively, and then enter the mass spectrometer for analysis.
- This solution is designed so that the high-speed airflow direction of the two solvent electrospray beams is consistent with the entrance direction of the mass spectrometer 16 to avoid affecting the transmission efficiency of the substance to be measured to the entrance of the mass spectrometer 16 and causing signal loss.
- the extraction ionization chamber 2 is made by 3D printing and has the characteristics of fast molding and manufacturing efficiency and long service life.
- the extraction ionization chamber 2 is a cylindrical cavity with an opening at the upper end; in this application, the upper opening of the cylindrical cavity is the sample spray droplet inlet of the extraction ionization chamber 2, and the upper end of the cylindrical cavity is connected to The bottom end of the high-frequency microporous oscillating plate 1 is connected, and the solvent spray droplet inlet and outlet are opened on the side wall of the cylindrical cavity.
- This application involves the construction of a new normal pressure ionization source device.
- the solution sample first comes into contact with the microporous oscillating plate and is rapidly atomized into micron-sized droplets, and then is sprayed with polar electrospray and weak polar electrospray (two paths)
- the droplets undergo collision extraction and charge transfer successively, extracting polar and non-polar substances in the ionized sample respectively, and then enter the mass spectrometer for analysis.
- This application provides a new ionization source technology and device for mass spectrometry analysis.
- the overall process flow of this application is shown in Figure 2.
- the continuous flow solution/droplet/cell sample is applied to the microporous oscillating plate through contact connection or dripping. Under the action of high-frequency oscillation, the solution sample, droplet sample or cell sample quickly passes through the microporous plate and is broken. Spray into micron-sized droplets and enter the extraction ionization chamber.
- DC high-voltage electricity successively triggers the atomization-free microliter electrospray of polar solvents and weakly polar solvents, which collides with the sample droplets in the extraction ionization chamber for extraction and charge transfer reactions to achieve polarity. Efficient ionization of weakly polar substances to be measured enters the mass spectrometer for analysis under the attraction of the vacuum negative pressure of the mass spectrometer.
- the microporous vibration piece can vibrate up and down at high frequency when driven by 24V DC voltage.
- the middle vibration piece is covered with micron-sized pores.
- For solution samples the moment the solution samples come into contact with the vibrating plate, they pass through the microporous plate under the action of high-frequency oscillation, are cut into micron-sized spray droplets, and vertically enter the semi-enclosed extraction ionization chamber; for cell samples, When the cell solution or droplet comes into contact with the vibrating plate, the cell membrane is instantly oscillated and fragmented.
- the organelles and cytoplasm pass through the microporous plate. Larger organelles such as mitochondria are further cut and fragmented, and intracellular substances are completely released into micron-sized sample droplets. middle.
- a Taylor cone spray is formed at the tip of the spray capillary (10 microns in diameter), producing micron-sized solvent spray droplets and solvents of different polarities.
- the polar and weakly polar electrosprays are successively introduced from one side of the extraction ionization chamber at a certain angle in the horizontal direction, and interact with the vertical sample spray droplets in the chamber to extract the ionization polarity and weakly polarity analytes respectively.
- the substance enters the mass spectrometer for analysis.
- High-frequency microhole oscillator 1 with optional diameter (10-30mm) and number of micropores (1000-3000 mesh), driven by DC 24V voltage.
- the sample solution penetrates the microporous plate under the action of high-frequency oscillation and is cut into a spray of micron-sized droplets.
- the cell membrane is also broken and intracellular substances are released; the sample droplets enter the extraction ionization chamber 2.
- Extraction ionization chamber 2 is made by 3D printing.
- the top is open, and the top is connected to the microporous oscillating plate, and the side wall has openings, which are respectively connected to the polar electrospray capillary 8, the weak polar electrospray capillary 12, and the mass spectrometer inlet transmission capillary 15; the extraction ionization chamber 2 is the spray intersection and The place where extractive ionization occurs.
- the sample solution syringe pump 3 provides power for sample solution transmission and regulates the flow rate.
- Sample solution transfer capillary 4 outer diameter 360 microns, inner diameter 50 microns.
- the polar solvent injection pump 5 provides power and regulates the flow rate for polar electrospray solvent transmission.
- Polar solvent transfer capillary 6 outer diameter 360 microns, inner diameter 50 microns.
- the metal union (that is, the polar solvent metal union 7) connects the polar solvent transmission capillary 6 and the polar electrospray capillary 8, and is also the application point of DC high voltage.
- Polar electrospray capillary 8 with an outer diameter of 360 microns, an inner diameter of 20 microns, and a tip inner diameter of 10 microns, generates polar electrospray under the action of DC high voltage (3-5kV), and the spray plume interacts with the sample in the extraction ionization chamber 2
- the droplets collide and extract the polar substances to be measured in the ionized sample droplets.
- the weakly polar solvent injection pump 9 provides power and adjusts the flow rate for the weakly polar electrospray solvent transmission.
- the metal union (that is, the weakly polar solvent metal union 11) connects the weakly polar solvent transmission capillary 10 and the weakly polar electrospray capillary 12, and is also the application point of DC high voltage.
- Weak polarity electrospray capillary 12 with an outer diameter of 360 microns, an inner diameter of 20 microns, and a tip inner diameter of 10 microns, generates weak polarity electrospray under the action of DC high voltage (4-6kV), and the spray plume is in the extraction ionization chamber 2 It interacts with the sample droplets and extracts the weakly polar substance to be measured in the ionized sample droplets.
- DC high voltage 4-6kV
- DC high voltage power supply 13 provides DC high voltage for polarity and weak polarity electrospray.
- the high-frequency switch 14 switches and outputs the high-voltage electricity and high-frequency switch provided by the DC high-voltage power supply 13 to the polar/weak-polar electrospray capillary to realize the alternating occurrence of polar and weak-polar electrospray, and extract the ionized sample droplets respectively.
- polar and weakly polar substances are used to realize the alternating occurrence of polar and weak-polar electrospray, and extract the ionized sample droplets respectively.
- the mass spectrometer inlet transmission capillary 15 transmits the polar and weakly polar test substances extracted and ionized in the extraction ionization chamber 2 to the mass spectrometer inlet under the vacuum negative pressure of the mass spectrometer for mass spectrometry analysis.
- the extraction ionization chamber 2 is connected to the mass spectrometer inlet transmission capillary 15. Turn on the polar solvent injection pump 5, the weakly polar solvent injection pump 9, the DC high-voltage power supply 13 and the high-frequency switch 14 until the solvent fills the capillary and forms a stable electrospray. Afterwards (about 2 minutes), turn on the high-frequency micropore vibrator 1. For solution samples, start the sample solution syringe pump 3, adjust the flow rate, and start mass spectrometry analysis; for droplets or cell samples, directly add droplets or cell-containing droplets to the high-frequency micropore oscillating plate 1, and start mass spectrometry. analyze.
- extraction ionization chamber 2 is processed by 3D printing, and other high-frequency microporous oscillators, DC high-voltage power supplies, transmission capillaries, electrospray capillaries, etc. are commercial parts.
- the cell membrane, organelles, etc. are fragmented and cut by micron-sized pores, and the intracellular substances are completely released into the sample droplets, enabling complete and efficient analysis of cellular substances.
- the design of dual electrospray extraction probes performs alternating electrospraying of polar and weakly polar solvents to extract polar and weakly polar substances in the ionized sample droplets respectively, maximizing the simultaneous ionization of multiple substances. analyze.
- the 3D printed semi-closed extraction ionization chamber is used to improve the stability and repeatability of extraction ionization.
Landscapes
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Engineering & Computer Science (AREA)
- Plasma & Fusion (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
- Electron Tubes For Measurement (AREA)
Abstract
本发明公开的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，将液滴碰撞和萃取电离发生在萃取电离腔体内，使得样本喷雾装置和溶剂电喷雾装置的喷雾角度以及与质谱仪入口之间的空间位置都是固定的，从而有助于提高了电喷雾萃取电离的稳定性和重复性。
Description
本申请要求于2022年04月08日提交中国专利局、申请号为202210365101.3、发明名称为“一种用于质谱分析的微孔震荡雾化电喷雾萃取电离装置”的中国专利申请的优先权，其全部内容通过引用结合在本申请中。
本申请涉及质谱分析技术领域，特别涉及一种用于质谱分析的微孔震荡雾化电喷雾萃取电离装置。
质谱仪是在电磁场作用下对带电离子进行分离分析的仪器，主要包括电离源、质量分析器、检测器等几个部分。电离源将待测物质电离为带电状态，是质谱分析的第一步也是关键步骤，因此电离源被称为质谱仪的心脏。
电喷雾电离源是最常见、应用最为广泛的一种电离源，含有待测物质的样本溶液流经毛细管，在毛细管的出口处施加直流高电压，同时毛细管同轴带有加热的雾化气。在电场力和雾化气双重作用下，溶剂分子在毛细管出口处会发生喷雾，雾化成微米级带有电荷的小液滴，经过溶剂蒸发和库伦爆炸，最终待测物质变为气态离子进入质谱仪被分析。
本申请，电喷雾萃取电离：由两路交叉的电喷雾构成的电喷雾萃取电离装置。本申请一路电喷雾是样本溶液，另一路电喷雾是萃取电离溶剂，在两路电喷雾的交汇点发生萃取和电荷转移，实现待测物质的萃取电离，然后进入质谱进行分析。也就是说，电喷雾萃取电离的样本溶液并不是直接电喷雾进入质谱，而是与另一路纯溶剂的电喷雾发生萃取和电荷转移而实现待测物质的电离，该技术方法降低了样本溶液中基质等对待测物质电离的干扰，不同极性的萃取溶剂对有不同极性的待测物分子有较好的萃取效果。
此外，电喷雾萃取电离是在敞开式环境中、两束雾化气辅助的电喷雾交叉碰撞发生的萃取电离过程，然而还存在以下缺点：
1、受环境气流等外界因素影响较大，稳定性差；
2、两束电喷雾角度以及与质谱入口之间的空间位置不好调节，重复性差；
3、萃取溶剂单一，无法实现极性物质和弱极性物质的同时分析；
4、样本溶液与萃取溶剂均是雾化气辅助的电喷雾，依赖气体钢瓶或串接气路，无法实现电离源装置的便携式集成和移动，同时气体使用成本较高；
5、两束电喷雾的高速气流方向与质谱仪入口方向不一致，会影响待测物质向质谱仪入口的传输效率，造成信号损失。
有鉴于此，本申请提供了一种用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，将液滴碰撞和萃取电离发生在萃取电离腔体内，而且也使得样本喷雾装置和溶剂电喷雾装置的喷雾角度以及与质谱仪入口之间的空间位置都是固定的，从而有助于提高了电喷雾萃取电离的稳定性和重复性。
为实现上述目的，本申请提供如下技术方案：
一种用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，包括样本喷雾装置、溶剂电喷雾装置和萃取电离腔体；
所述萃取电离腔体分别开设有样本喷雾液滴入口、溶剂喷雾液滴入口和出口；所述样本喷雾液滴入口向所述萃取电离腔体内腔的延长线，与所述溶剂喷雾液滴入口向所述萃取电离腔体内腔的延长线相交；
所述萃取电离腔体的样本喷雾液滴入口与所述样本喷雾装置的出口相连，溶剂喷雾液滴入口与所述溶剂电喷雾装置的出口相连，出口用于与质谱仪的入口相连。
优选地，所述样本喷雾装置包括：
设置于所述萃取电离腔体的样本喷雾液滴入口，且用于注入或滴入样本的高频微孔震荡片。
优选地，所述样本喷雾液滴入口开设于所述萃取电离腔体的顶端，所述溶剂喷雾液滴入口开设于所述萃取电离腔体的侧壁。
优选地，所述样本喷雾装置还包括样本溶液注射泵和样本溶液传输毛细管；
所述样本溶液传输毛细管的进口端与所述样本溶液注射泵的出口端相连，出口端用于对准所述高频微孔震荡片。
优选地，所述溶剂喷雾液滴入口包括极性溶剂喷雾液滴入口和弱极性溶剂喷雾液滴入口；
所述溶剂电喷雾装置包括极性溶剂电喷雾装置和弱极性溶剂电喷雾装置；所述极性溶剂电喷雾装置的出口与所述极性溶剂喷雾液滴入口相连，所述弱极性溶剂电喷雾装置的出口与所述弱极性溶剂喷雾液滴入口相连。
优选地，所述极性溶剂电喷雾装置包括极性溶剂喷雾主体；
所述弱极性溶剂电喷雾装置包括弱极性溶剂喷雾主体；
所述溶剂电喷雾装置还包括直流高压电源和高频切换开关；
所述直流高压电源与所述高频切换开关通讯连接，所述高频切换开关分别与所述极性溶剂喷雾主体的毛细管和所述弱极性溶剂喷雾主体的毛细管电连接。
优选地，所述极性溶剂喷雾主体包括极性溶剂注射泵和极性溶剂毛细管；所述极性溶剂毛细管的进口端与所述极性溶剂注射泵的出口端相连，出口端与所述极性溶剂喷雾液滴入口相连，且与所述高频切换开关电连接；
所述弱极性溶剂喷雾主体包括弱极性溶剂注射泵和弱极性溶剂毛细管；所述弱极性溶剂毛细管的进口端与所述弱极性溶剂注射泵的出口端相连，出口端与所述弱极性溶剂喷雾液滴入口相连，且与所述高频切换开关电连接。
优选地，所述极性溶剂喷雾主体还包括极性溶剂金属二通；
所述极性溶剂金属二通接入于所述极性溶剂毛细管的中间部分，且与所述高频切换开关电连接；
所述弱极性溶剂喷雾主体还包括弱极性溶剂金属二通；所述弱极性溶剂金属二通接入于所述弱极性溶剂毛细管的中间部分，且与所述高频切换开关电连接。
优选地，所述极性溶剂喷雾液滴入口和所述弱极性溶剂喷雾液滴入口开设于所述萃取电离腔体的同一侧壁，所述出口开设于所述萃取电离腔体的另一侧壁，且分别与所述极性溶剂喷雾液滴入口和所述弱极性溶剂喷雾液滴入口相对设置；
所述极性溶剂毛细管的出口端沿水平方向向下倾斜与所述极性溶剂喷雾液滴入口相连，所述弱极性溶剂毛细管的出口端沿水平方向向上倾斜与所述弱极性溶剂喷雾液滴入口相连。
优选地，所述萃取电离腔体由3D打印加工制成。
从上述的技术方案可以看出，本申请提供的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置中，将液滴碰撞和萃取电离发生在萃取电离腔体内，而且也使得样本喷雾装置和溶剂电喷雾装置的喷雾角度以及与质谱仪入口之间的空间位置都是固定的，从而有助于提高了电喷雾萃取电离的稳定性和重复性。
为了更清楚地说明本申请实施例或现有技术中的技术方案，下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本申请的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。
图1为本申请实施例提供的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置的结构简图；
图2为本申请实施例提供的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置的流程图。
本申请，1为高频微孔震荡片，2为萃取电离腔体，3为样本溶液注射泵，4为样本溶液传输毛细管，5为极性溶剂注射泵，6为极性溶剂传输毛细管，7为极性溶剂金属二通，8为极性电喷雾毛细管，9为弱极性溶剂注射泵，10为弱极性溶剂传输毛细管，11为弱极性溶剂金属二通，12为弱极性电喷雾毛细管，13为直流高压电源，14为高频切换开关，15为质谱仪入口传输毛细管，16为质谱仪。
本申请的实施方式
下面将结合本申请实施例中的附图，对本申请实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本申请一部分实施例，而不是全部的实施例。基于本申请中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本申请保护的范围。
本申请实施例提供的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，如图1所示，包括样本喷雾装置、溶剂电喷雾装置和萃取电离腔体（2）；
萃取电离腔体2分别开设有样本喷雾液滴入口、溶剂喷雾液滴入口和出口；样本喷雾液滴入口向萃取电离腔体2内腔的延长线，与溶剂喷雾液滴入口向萃取电离腔体2内腔的延长线相交；
萃取电离腔体2的样本喷雾液滴入口与样本喷雾装置的出口相连，溶剂喷雾液滴入口与溶剂电喷雾装置的出口相连，出口用于与质谱仪16的入口相连。
需要说明的是，样本喷雾液滴入口的内侧延长线与溶剂喷雾液滴入口的内侧延长线相交，以便于使得样本喷雾装置和溶剂电喷雾装置这两路的喷雾液滴在萃取电离腔体2内形成交汇点，进而使得这两路的喷雾液滴在萃取电离腔体2内发生碰撞萃取和电荷转移，萃取电离样本中的待测物质，然后在在质谱仪16真空负压作用下，再将萃取电离腔体2内萃取电离的待测物质传输到质谱仪16内进行质谱分析。也就是说，本方案的电喷雾萃取电离发生在萃取电离腔体2内，可避免受环境气流等外界因素影响，而且这两路喷雾液滴的角度以及与质谱仪16入口之间的空间位置都是固定的，从而有助于提高了电喷雾萃取电离的稳定性和重复性。
从上述的技术方案可以看出，本申请实施例提供的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置中，将液滴碰撞和萃取电离发生在萃取电离腔体内，而且也使得样本喷雾装置和溶剂电喷雾装置的喷雾角度以及与质谱仪入口之间的空间位置都是固定的，从而有助于提高了电喷雾萃取电离的稳定性和重复性。
在本方案中，如图1所示，样本喷雾装置包括：
设置于萃取电离腔体2的样本喷雾液滴入口，且用于注入或滴入样本的高频微孔震荡片1。本申请，将样本施加于高频微孔震荡片1上，在高频振荡作用下，样本迅速穿过高频微孔震荡片1的微孔片，被破碎成微米级细小的液滴喷雾，然后再进入萃取电离腔体2内。此外，本方案选用高频微孔震荡片1作为样本喷雾装置，以便于将样本雾化成微米级液滴羽束，不仅适用于连续流动的溶液样本，还适用于液滴样本、细胞样本等，而且细胞样本经过高频震荡片1时，细胞膜、细胞器等被微米级细孔碎裂切割，胞内物质完全释放到样本液滴中，可实现完整、高效的细胞物质分析。
具体地，样本喷雾液滴入口开设于萃取电离腔体2的顶端，溶剂喷雾液滴入口开设于萃取电离腔体2的侧壁。本方案如此设计，以便于使得样本喷雾液滴能够垂直自然落入萃取电离腔体2内。此外，高频微孔震荡片1的底端与萃取电离腔体2的顶端相连。
进一步地，如图1所示，样本喷雾装置还包括样本溶液注射泵3和样本溶液传输毛细管4；
样本溶液传输毛细管4的进口端与样本溶液注射泵3的出口端相连，本申请，样本溶液注射泵3为步进电机微量注射泵，搭配1mL规格的注射器，可以设定输送样本溶液流量，注射器通过步进电机微量注射泵的驱动预先抽取样本溶液，然后再将注射器的出口端与样本溶液传输毛细管4的进口端相连以待输送样本溶液；样本溶液传输毛细管4的出口端用于对准高频微孔震荡片1，即样本溶液传输毛细管4的出口端与高频微孔震荡片1的微孔片形成对位配合。本方案如此设计，以便于实现样本溶液对高频微孔震荡片1的自动注射，而且还采用无雾化气辅助的样本溶液注射泵3为样本溶液传输提供动力，即使得该样本喷雾装置为无雾化气辅助的样本喷雾装置，从而有助于摆脱了使用钢瓶气体的限制，降低了使用成本，且使得本装置易于便携式集成和移动。
在本方案中，溶剂喷雾液滴入口包括极性溶剂喷雾液滴入口和弱极性溶剂喷雾液滴入口；
溶剂电喷雾装置包括极性溶剂电喷雾装置和弱极性溶剂电喷雾装置；极性溶剂电喷雾装置的出口与极性溶剂喷雾液滴入口相连，弱极性溶剂电喷雾装置的出口与所述弱极性溶剂喷雾液滴入口相连。本方案如此设计，一方面使得极性溶剂电喷雾装置在直流高电压作用下产生极性溶剂电喷雾，而且在萃取电离腔体2内与样本喷雾液滴发生交互碰撞，并萃取电离样本液滴中极性待测物质；另一方面使得弱极性溶剂电喷雾装置在直流高电压作用下产生弱极性溶剂电喷雾，而且在萃取电离腔体2内与样本喷雾液滴发生交互碰撞，并萃取电离样本液滴中弱极性待测物质。也就是说，本方案采用两个不同极性的溶剂电喷雾装置，以便于能够萃取电离样本液滴中的极性和弱极性物质，最大限度地实现了极性物质和弱极性物质的同时电离分析。
具体地，极性溶剂电喷雾装置包括极性溶剂喷雾主体；
弱极性溶剂电喷雾装置包括弱极性溶剂喷雾主体；
如图1所示，溶剂电喷雾装置还包括直流高压电源13和高频切换开关14；
直流高压电源13与高频切换开关14通讯连接，高频切换开关14分别与极性溶剂喷雾主体的毛细管和弱极性溶剂喷雾主体的毛细管电连接。本方案如此设计，以便于通过高频切换开关14将直流高压电源13提供的高压电高频切换输出给极性溶剂喷雾主体和弱极性溶剂喷雾主体的毛细管，实现极性和弱极性溶剂电喷雾的交替发生，进而便于分别萃取电离样本液滴中的极性和弱极性物质。也就是说，本方案采用不同极性的双溶剂电喷雾装置，以便于进行极性、弱极性溶剂交替电喷雾，方便分别萃取电离样本液滴中的极性和弱极性物质，从而最大限度地实现了多种物质的同时电离分析。此外，不难看出的是，本方案的极性溶剂电喷雾装置和弱极性溶剂电喷雾装置共用一个直流高压电源13。
进一步地，如图1所示，极性溶剂喷雾主体包括极性溶剂注射泵5和极性溶剂毛细管；极性溶剂毛细管的进口端与极性溶剂注射泵5的出口端相连，本申请，极性溶剂注射泵5为步进电机微量注射泵，搭配1mL规格的注射器，可以设定输送极性溶剂流量，注射器通过步进电机微量注射泵的驱动预先抽取极性溶剂，然后再将注射器的出口端与极性溶剂毛细管的进口端相连以待输送极性溶剂；极性溶剂毛细管的出口端与极性溶剂喷雾液滴入口相连，且与高频切换开关14电连接；
弱极性溶剂喷雾主体包括弱极性溶剂注射泵9和弱极性溶剂毛细管；弱极性溶剂毛细管的进口端与弱极性溶剂注射泵9的出口端相连，本申请，弱极性溶剂注射泵9为步进电机微量注射泵，搭配1mL规格的注射器，可以设定输送弱极性溶剂流量，注射器通过步进电机微量注射泵的驱动预先抽取弱极性溶剂，然后再将注射器的出口端与弱极性溶剂毛细管的进口端相连以待输送弱极性溶剂；弱极性溶剂毛细管的出口端与弱极性溶剂喷雾液滴入口相连，且与高频切换开关14电连接。本方案如此设计，以使得这两种溶剂喷雾主体均采用无雾化气辅助的溶剂注射泵为电喷雾溶剂传输提供动力，即使得这两种溶剂电喷雾装置均为无雾化气辅助的溶剂电喷雾装置，从而有助于摆脱了使用钢瓶气体的限制，降低了使用成本，且使得本装置易于便携式集成和移动。
再进一步地，如图1所示，极性溶剂喷雾主体还包括极性溶剂金属二通7；
极性溶剂金属二通7接入于极性溶剂毛细管的中间部分，且与高频切换开关14电连接；
弱极性溶剂喷雾主体还包括弱极性溶剂金属二通11；弱极性溶剂金属二通11接入于弱极性溶剂毛细管的中间部分，且与高频切换开关14电连接。本方案如此设计，以便于使得这两种溶剂喷雾主体的毛细管与直流高电压形成导通。此外，如图1所示，弱极性溶剂毛细管包括极性溶剂传输毛细管6和极性电喷雾毛细管8；本申请，极性溶剂传输毛细管6的进口端与极性溶剂注射泵5的出口端相连，出口端与极性溶剂金属二通7的一端相连；极性电喷雾毛细管8的进口端与极性溶剂金属二通7的另一端相连，出口端与极性溶剂喷雾液滴入口相连；另外，弱极性溶剂毛细管包括弱极性溶剂传输毛细管10和弱极性电喷雾毛细管12；本申请，弱极性溶剂传输毛细管10的进口端与弱极性溶剂注射泵9的出口端相连，出口端与弱极性溶剂金属二通11的一端相连；弱极性电喷雾毛细管12的进口端与弱极性溶剂金属二通11的另一端相连，出口端与弱极性溶剂喷雾液滴入口相连。
在本方案中，如图1所示，极性溶剂喷雾液滴入口和弱极性溶剂喷雾液滴入口开设于萃取电离腔体2的同一侧壁，出口开设于萃取电离腔体2的另一侧壁，且分别与极性溶剂喷雾液滴入口和弱极性溶剂喷雾液滴入口相对设置；
极性溶剂毛细管的出口端沿水平方向向下倾斜与极性溶剂喷雾液滴入口相连，弱极性溶剂毛细管的出口端沿水平方向向上倾斜与弱极性溶剂喷雾液滴入口相连。也就是说，本方案的极性和弱极性溶剂电喷雾先后沿水平方向以一定角度从萃取电离腔体2一侧壁引入，并在萃取电离腔体2内与垂直落下的样本喷雾液滴发生交互碰撞，分别萃取电离极性和弱极性的待测物质，然后再进入质谱仪进行分析。本方案如此设计，以使得两束溶剂电喷雾的高速气流方向与质谱仪16入口方向保持一致，避免影响待测物质向质谱仪16入口的传输效率，以防造成信号损失。
具体地，萃取电离腔体2由3D打印加工制成，具有成型制造效率快、使用寿命高等特点。作为优选，萃取电离腔体2为上端设有开口的圆柱形腔体；本申请，圆柱形腔体的上端开口即为萃取电离腔体2的样本喷雾液滴入口，圆柱形腔体的上端与高频微孔震荡片1底端相连，溶剂喷雾液滴入口和出口开设于该圆柱形腔体的侧壁。
下面结合具体实施例对本方案作进一步介绍：
本申请涉及构建一种新的常压电离源装置，溶液样本首先与微孔震荡片接触，被迅速雾化成微米级小液滴，然后与极性电喷雾和弱极性电喷雾（两路）液滴先后发生碰撞萃取和电荷转移，分别萃取电离样本中极性和非极性物质，之后再进入质谱仪进行分析。
本申请提供了一种用于质谱分析的新型电离源技术与装置，本申请整体作用流程如图2所示。连续流溶液/液滴/细胞样本通过接触连接或滴加的方式被施加到微孔震荡片上，在高频振荡作用下，溶液样本、液滴样本或细胞样本迅速穿过微孔片，被破碎成微米级细小的液滴喷雾，进入萃取电离腔体。与此同时，直流高压电先后触发极性溶剂和弱极性溶剂的无雾化气辅助的微升电喷雾，在萃取电离腔体内与样本液滴发生碰撞萃取和电荷转移反应，实现极性和弱极性待测物质的高效电离，在质谱仪真空负压的吸引作用下进入质谱仪进行分析。
本装置工作原理：
微孔震动片可以在24V直流电压驱动下实现高频上下震动，中间震动片布满微米级大小的细孔。对于溶液样本，溶液样本与震动片接触的瞬间便在高频振荡作用下穿过微孔片，被切割成微米大小的喷雾液滴，垂直进入半封闭的萃取电离腔体；对于细胞样本，含细胞的溶液或液滴与震动片接触，细胞膜被瞬间振荡碎裂，细胞器和细胞质穿过微孔片，线粒体等较大的细胞器被进一步切割碎裂，胞内物质彻底释放到微米级样本液滴中。
与此同时，在3-6kV直流高压产生的电场力和库仑力作用下，在喷雾毛细管的尖端（直径10微米）形成泰勒锥喷雾，产生微米级大小的溶剂喷雾液滴，不同极性的溶剂产生不同极性的电喷雾羽束。极性和弱极性电喷雾先后沿水平方向以一定角度从萃取电离腔体一侧引入，在腔体内与垂直的样本喷雾液滴发生交互碰撞，分别萃取电离极性和弱极性的待测物质，进入质谱仪进行分析。
本装置结构与部件功能：
本申请所述装置结构示意图如图1所示，本申请：
高频微孔震荡片1，直径大小（10-30mm）、微孔数目（1000-3000目）可选，通过直流24V电压驱动。工作状态时，样本溶液在高频振荡作用下穿透微孔片，被切割成微米级液滴喷雾。细胞样本分析时，细胞膜也被破碎，胞内物质释放出来；样本液滴进入萃取电离腔体2。
萃取电离腔体2，由3D打印加工制成。顶端开口，顶端与微孔震荡片相连，侧壁有开口，分别与极性电喷雾毛细管8、弱极性电喷雾毛细管12、质谱仪入口传输毛细管15相连；萃取电离腔体2是喷雾交汇和萃取电离发生的场所。
样本溶液注射泵3，为样本溶液传输提供动力、调节流量。
样本溶液传输毛细管4，外径360微米，内径50微米。
极性溶剂注射泵5，为极性电喷雾溶剂传输提供动力、调节流量。
极性溶剂传输毛细管6，外径360微米，内径50微米。
金属两通（即为极性溶剂金属两通7），连接极性溶剂传输毛细管6和极性电喷雾毛细管8，同时是直流高电压的施加点。
极性电喷雾毛细管8，外径360微米，内径20微米，尖端内径10微米，在直流高电压（3-5kV）作用下产生极性电喷雾，喷雾羽束在萃取电离腔体2内与样本液滴发生交互碰撞，并萃取电离样本液滴中极性待测物质。
弱极性溶剂注射泵9，为弱极性电喷雾溶剂传输提供动力、调节流量。
弱极性溶剂传输毛细管10，外径360微米，内径50微米。
金属两通（即为弱极性溶剂金属两通11），连接弱极性溶剂传输毛细管10和弱极性电喷雾毛细管12，同时是直流高电压的施加点。
弱极性电喷雾毛细管12，外径360微米，内径20微米，尖端内径10微米，在直流高电压（4-6kV）作用下产生弱极性电喷雾，喷雾羽束在萃取电离腔体2内与样本液滴发生交互碰撞，并萃取电离样本液滴中弱极性待测物质。
直流高压电源13，为极性和弱极性电喷雾提供直流高压。
高频切换开关14，将直流高压电源13提供的高压电高频切换输出给极性/弱极性电喷雾毛细管，实现极性和弱极性电喷雾的交替发生，分别萃取电离样本液滴中的极性和弱极性物质。
质谱仪入口传输毛细管15，在质谱仪真空负压作用下，将萃取电离腔体内2萃取电离的极性和弱极性待测物质传输到质谱仪入口，进行质谱分析。
本装置工作流程：
萃取电离腔体2与质谱仪入口传输毛细管15相连，开启极性溶剂注射泵5、弱极性溶剂注射泵9、直流高压电源13以及高频切换开关14，待溶剂充满毛细管并形成稳定电喷雾后（约2分钟），开启高频微孔震荡片1。对于溶液样本，开启样本溶液注射泵3，调整好流量，开始质谱分析；对于液滴或细胞样本，直接将液滴或含细胞的液滴滴加在高频微孔震荡片1上，开始质谱分析。
此外，萃取电离腔体2由3D打印方式加工，其它高频微孔震荡片、直流高压电源、传输毛细管、电喷雾毛细管等为商品件。
本申请的优点：
1、采用高频震荡片将样本雾化成微米级液滴羽束，不仅适用于连续流动的溶液样本，还适用于液滴样本、细胞样本等。
2、细胞样本经过高频震荡片，细胞膜、细胞器等被微米级细孔碎裂切割，胞内物质完全释放到样本液滴中，可实现完整、高效的细胞物质分析。
3、双电喷雾萃取探针的设计，进行极性、弱极性溶剂交替电喷雾，分别萃取电离样本液滴中的极性和弱极性物质，最大限度地实现了多种物质的同时电离分析。
4、采用高频震荡片雾化样本溶液，采用无雾化气辅助的微升电喷雾雾化萃取溶剂，均摆脱了使用钢瓶气体的限制，降低了使用成本，且易于集成、移动。
5、液滴碰撞和萃取电离发生在3D打印的半封闭腔体内，空间位置和相对角度都是固定的，提高了该技术方法的稳定性和可重复性。
本申请的关键点和欲保护点：
1、采用高频震荡片雾化样本，进行连续流液体、液滴、细胞样本的高效电喷雾萃取电离。
2、采用高频振荡片碎裂细胞样本并雾化成样本液滴，进行胞内物质的完整、高效分析。
3、采用极性、弱极性溶剂两个交替电喷雾实现极性和弱极性待测物质的同时萃取电离。
4、采用3D打印的半封闭萃取电离腔体，提高萃取电离的稳定性和重复性。
本说明书中各个实施例采用递进的方式描述，每个实施例重点说明的都是与其他实施例的不同之处，各个实施例之间相同相似部分互相参见即可。
对所公开的实施例的上述说明，使本领域专业技术人员能够实现或使用本申请。对这些实施例的多种修改对本领域的专业技术人员来说将是显而易见的，本文中所定义的一般原理可以在不脱离本申请的精神或范围的情况下，在其它实施例中实现。因此，本申请将不会被限制于本文所示的这些实施例，而是要符合与本文所公开的原理和新颖特点相一致的最宽的范围。
Claims (20)
- 一种用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，包括样本喷雾装置、溶剂电喷雾装置和萃取电离腔体（2）；所述萃取电离腔体（2）分别开设有样本喷雾液滴入口、溶剂喷雾液滴入口和出口；所述样本喷雾液滴入口向所述萃取电离腔体（2）内腔的延长线，与所述溶剂喷雾液滴入口向所述萃取电离腔体（2）内腔的延长线相交；所述萃取电离腔体（2）的样本喷雾液滴入口与所述样本喷雾装置的出口相连，溶剂喷雾液滴入口与所述溶剂电喷雾装置的出口相连，出口用于与质谱仪（16）的入口相连。
- 根据权利要求1所述的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，其中，所述样本喷雾装置包括：设置于所述萃取电离腔体（2）的样本喷雾液滴入口，且用于注入或滴入样本的高频微孔震荡片（1）。
- 根据权利要求2所述的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，其中，所述样本喷雾液滴入口开设于所述萃取电离腔体（2）的顶端，所述溶剂喷雾液滴入口开设于所述萃取电离腔体（2）的侧壁。
- 根据权利要求2所述的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，其中，所述高频微孔震荡片（1）的底端与所述萃取电离腔体（2）的顶端相连。
- 根据权利要求2所述的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，其中，所述样本喷雾装置还包括样本溶液注射泵（3）和样本溶液传输毛细管（4）；所述样本溶液传输毛细管（4）的进口端与所述样本溶液注射泵（3）的出口端相连，出口端用于对准所述高频微孔震荡片（1）。
- 根据权利要求5所述的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，其中，所述样本溶液注射泵（3）为步进电机微量注射泵。
- 根据权利要求1所述的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，其中，所述溶剂喷雾液滴入口包括极性溶剂喷雾液滴入口和弱极性溶剂喷雾液滴入口；所述溶剂电喷雾装置包括极性溶剂电喷雾装置和弱极性溶剂电喷雾装置；所述极性溶剂电喷雾装置的出口与所述极性溶剂喷雾液滴入口相连，所述弱极性溶剂电喷雾装置的出口与所述弱极性溶剂喷雾液滴入口相连。
- 根据权利要求7所述的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，其中，所述极性溶剂电喷雾装置包括极性溶剂喷雾主体；所述弱极性溶剂电喷雾装置包括弱极性溶剂喷雾主体；所述溶剂电喷雾装置还包括直流高压电源（13）和高频切换开关（14）；所述直流高压电源（13）与所述高频切换开关（14）通讯连接，所述高频切换开关（14）分别与所述极性溶剂喷雾主体的毛细管和所述弱极性溶剂喷雾主体的毛细管电连接。
- 根据权利要求8所述的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，其中，所述极性溶剂喷雾主体包括极性溶剂注射泵（5）和极性溶剂毛细管；所述极性溶剂毛细管的进口端与所述极性溶剂注射泵（5）的出口端相连，出口端与所述极性溶剂喷雾液滴入口相连，且与所述高频切换开关（14）电连接；所述弱极性溶剂喷雾主体包括弱极性溶剂注射泵（9）和弱极性溶剂毛细管；所述弱极性溶剂毛细管的进口端与所述弱极性溶剂注射泵（9）的出口端相连，出口端与所述弱极性溶剂喷雾液滴入口相连，且与所述高频切换开关（14）电连接。
- 根据权利要求9所述的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，其中，所述极性溶剂注射泵（5）为步进电机微量注射泵。
- 根据权利要求9所述的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，其中，所述弱极性溶剂注射泵（9）步进电机微量注射泵。
- 根据权利要求9所述的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，其中，所述极性溶剂喷雾主体还包括极性溶剂金属二通（7）；所述极性溶剂金属二通（7）接入于所述极性溶剂毛细管的中间部分，且与所述高频切换开关（14）电连接；所述弱极性溶剂喷雾主体还包括弱极性溶剂金属二通（11）；所述弱极性溶剂金属二通（11）接入于所述弱极性溶剂毛细管的中间部分，且与所述高频切换开关（14）电连接。
- 根据权利要求12所述的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，其中，所述弱极性溶剂毛细管包括极性溶剂传输毛细管（6）和极性电喷雾毛细管（8）。
- 根据权利要求13所述的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，其中，所述极性溶剂传输毛细管（6）的进口端与所述极性溶剂注射泵（5）的出口端相连，出口端与所述极性溶剂金属二通（7）的一端相连。
- 根据权利要求13所述的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，其中，所述极性电喷雾毛细管（8）的进口端与极性溶剂金属二通（7）的另一端相连，出口端与所述极性溶剂喷雾液滴入口相连。
- 根据权利要求12所述的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，其中，所述弱极性溶剂毛细管包括弱极性溶剂传输毛细管（10）和弱极性电喷雾毛细管（12）。
- 根据权利要求16所述的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，其中，所述弱极性溶剂传输毛细管（10）的进口端与所述弱极性溶剂注射泵（9）的出口端相连，出口端与所述弱极性溶剂金属二通（11）的一端相连。
- 根据权利要求16所述的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，其中，所述弱极性电喷雾毛细管（12）的进口端与所述弱极性溶剂金属二通（11）的另一端相连，出口端与所述弱极性溶剂喷雾液滴入口相连。
- 根据权利要求9所述的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，其中，所述极性溶剂喷雾液滴入口和所述弱极性溶剂喷雾液滴入口开设于所述萃取电离腔体（2）的同一侧壁，所述出口开设于所述萃取电离腔体（2）的另一侧壁，且分别与所述极性溶剂喷雾液滴入口和所述弱极性溶剂喷雾液滴入口相对设置；所述极性溶剂毛细管的出口端沿水平方向向下倾斜与所述极性溶剂喷雾液滴入口相连，所述弱极性溶剂毛细管的出口端沿水平方向向上倾斜与所述弱极性溶剂喷雾液滴入口相连。
- 根据权利要求1所述的用于质谱分析的微孔震荡雾化电喷雾萃取电离装置，其中，所述萃取电离腔体（2）由3D打印加工制成。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210365101.3 | 2022-04-08 | ||
| CN202210365101.3A CN114724920A (zh) | 2022-04-08 | 2022-04-08 | 一种用于质谱分析的微孔震荡雾化电喷雾萃取电离装置 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2023193481A1 true WO2023193481A1 (zh) | 2023-10-12 |
Family
ID=82241369
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CN2022/141856 WO2023193481A1 (zh) | 2022-04-08 | 2022-12-26 | 一种用于质谱分析的微孔震荡雾化电喷雾萃取电离装置 |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN114724920A (zh) |
| WO (1) | WO2023193481A1 (zh) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114724920A (zh) * | 2022-04-08 | 2022-07-08 | 中国科学院深圳先进技术研究院 | 一种用于质谱分析的微孔震荡雾化电喷雾萃取电离装置 |
| GB2621634A (en) * | 2022-08-19 | 2024-02-21 | Vibrat Ion Ltd | Aerosolisation system and methods of use thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103258711A (zh) * | 2013-05-21 | 2013-08-21 | 中国科学院上海有机化学研究所 | 一种溶剂辅助电喷雾离子化装置及使用该装置实现电喷雾离子化的方法 |
| CN111653471A (zh) * | 2020-06-05 | 2020-09-11 | 紫谱艾迪(苏州)科技有限公司 | 一种电喷雾萃取真空紫外光复合电离源 |
| CN112309823A (zh) * | 2020-11-13 | 2021-02-02 | 广州禾信仪器股份有限公司 | 质谱检测系统及离子源装置 |
| CN112614773A (zh) * | 2020-12-28 | 2021-04-06 | 广州禾信仪器股份有限公司 | 质谱离子源进样装置 |
| CN114724920A (zh) * | 2022-04-08 | 2022-07-08 | 中国科学院深圳先进技术研究院 | 一种用于质谱分析的微孔震荡雾化电喷雾萃取电离装置 |
-
2022
- 2022-04-08 CN CN202210365101.3A patent/CN114724920A/zh active Pending
- 2022-12-26 WO PCT/CN2022/141856 patent/WO2023193481A1/zh unknown
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103258711A (zh) * | 2013-05-21 | 2013-08-21 | 中国科学院上海有机化学研究所 | 一种溶剂辅助电喷雾离子化装置及使用该装置实现电喷雾离子化的方法 |
| CN111653471A (zh) * | 2020-06-05 | 2020-09-11 | 紫谱艾迪(苏州)科技有限公司 | 一种电喷雾萃取真空紫外光复合电离源 |
| CN112309823A (zh) * | 2020-11-13 | 2021-02-02 | 广州禾信仪器股份有限公司 | 质谱检测系统及离子源装置 |
| CN112614773A (zh) * | 2020-12-28 | 2021-04-06 | 广州禾信仪器股份有限公司 | 质谱离子源进样装置 |
| CN114724920A (zh) * | 2022-04-08 | 2022-07-08 | 中国科学院深圳先进技术研究院 | 一种用于质谱分析的微孔震荡雾化电喷雾萃取电离装置 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114724920A (zh) | 2022-07-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2023193481A1 (zh) | 一种用于质谱分析的微孔震荡雾化电喷雾萃取电离装置 | |
| US9618488B2 (en) | Interfacing capillary electrophoresis to a mass spectrometer via an impactor spray ionization source | |
| US9514924B2 (en) | Droplet manipulation using gas-phase standing-wave ultrasound fields in MS sources | |
| JP4167593B2 (ja) | エレクトロスプレイイオン化質量分析装置及びその方法 | |
| EP2666182B1 (en) | Synchronization of ion generation with cycling of a discontinuous atmospheric interface | |
| CA2184982C (en) | Electrospray and atmospheric pressure chemical ionization sources | |
| CN102709147B (zh) | 一种电喷雾离子源及质谱仪 | |
| WO2018188172A1 (zh) | 一种真空电喷雾离子源及质谱仪 | |
| US9704699B2 (en) | Hybrid ion source and mass spectrometric device | |
| US7812308B2 (en) | Mass spectrometer | |
| CN106876241A (zh) | 超声雾化大气压辉光放电电离装置 | |
| CN107238654B (zh) | 一种离子化装置 | |
| JPH0982269A (ja) | 溶液の質量分析に関する方法と装置 | |
| JP7011736B2 (ja) | 複数ガス流のイオン化装置 | |
| CN104124131A (zh) | 质谱离子源及质谱仪 | |
| CN209591975U (zh) | 一种用于质谱仪的离子源装置 | |
| CN109979797B (zh) | 一种用于质谱仪的离子源装置及其使用方法 | |
| CN209544279U (zh) | 一种化学反应中间体质谱检测装置 | |
| JP2005197141A (ja) | 質量分析装置 | |
| CN114724919A (zh) | 一种用于不同极性物质同时质谱分析的复合电离源装置 | |
| CN203300595U (zh) | 质谱离子源及质谱仪 | |
| CN217544538U (zh) | 二次电喷雾电离源装置、气体样品引入系统和试剂雾化器 | |
| CN211150508U (zh) | 一种气相质谱仪离子源结构 | |
| JP3353752B2 (ja) | イオン源 | |
| CN204228671U (zh) | 一种开放型分子加合同位素离子发生器 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 22936406 Country of ref document: EP Kind code of ref document: A1 |