Ion-induced spray ionization method and device

Abstract

The present invention discloses an ion-induced spray ionization method and device, wherein the ion-induced spray ionization method first generates charged induced ions in an auxiliary solvent by high pressure, and then causes the induced ions to exchange charge with a sample in a capillary to ionize the sample. The ion-induced spray ionization device comprises an induced ion generating device, a capillary and a mass spectrometry injection channel, wherein the induced ion generating device comprises an auxiliary solvent channel, the auxiliary solvent channel is connected to a high-voltage generating device, the outlet end of the auxiliary solvent channel is connected to the end of the capillary, the tip of the capillary is located on the axis of the mass spectrometry injection channel, and the capillary is non-conductive. The present invention can effectively solve the problems of easy in-source oxidation and poor compatibility of ionized solvents in traditional ESI, and has good ionization effect on compounds with low polarity and compounds prone to redox reactions, and has good compatibility with ionized solvents, and can be used for trace analysis and detection.

Description

Technical Field

[0001] The invention relates to an ion-induced spray ionization method and device, belonging to the technical field of mass spectrometry analysis. Background Art

[0002] Mass spectrometry (MS) is an important analytical tool that can analyze complex mixtures and provide information about molecular weight, elemental composition and chemical structure of the analyte. It has high specificity and sensitivity. The basic principle of mass spectrometry is to ionize the components in the sample in the ion source to generate positively charged ions with different charge-to-mass ratios. After the acceleration electric field, an ion beam is formed and enters the mass analyzer. Then, in the mass analyzer, the electric field and magnetic field are used to cause opposite velocity dispersion, and they are focused separately to obtain a mass spectrum to determine their mass. Therefore, ionization technology has an important influence on the results of mass spectrometry analysis. In recent years, with the continuous innovation and improvement of compound desorption and ionization technology and mass analyzers, mass spectrometry has become one of the fastest-growing analytical technologies. At present, mass spectrometry technology is more and more widely used in chemistry and chemical engineering, biology and life sciences, medicine, pharmacy, materials science, environmental protection and other fields.

[0003] At present, the commonly used ionization methods in mass spectrometry mainly include electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and matrix assisted laser desorption ionization (MALDI). Among them, ESI is the most widely used.

[0004] Electrospray ionization (ESI) is an ionization method proposed by American scientist John Finn. It has become the most widely used ionization method in mass spectrometry because of its ability to ionize highly polar, non-volatile and thermally unstable compounds while maintaining their integrity and the ability to obtain multi-charged ions. John Finn also won the Nobel Prize in Chemistry in 2002. ESI is a soft ionization technology based on "energy explosion". Its process can be briefly described as follows: the analyte dissolved in a polar solvent is introduced into a capillary with a high voltage of 3-4kV at the end. Under the action of high electric field and nebulizer gas, aerosol spray occurs, charged droplets are generated, and ions are gradually formed during the desolvation process.

[0005] As mass spectrometry analysis develops towards micro- and trace detection, ESI technology is also constantly advancing with the times. New ionization methods such as Nano-ESI and induction ESI have emerged one after another. These ionization methods are mainly based on the ESI principle, using extremely fine capillaries and removing atomizing gas, so that they can analyze nl or even pl level samples.

[0006] However, the above-mentioned electrospray ionization technology still has many defects. For example, during the ESI process, samples are prone to oxidation in the source, and some samples that are prone to redox are prone to redox reactions, making it difficult to obtain the original ion signal of the sample; the compatible solvent range is very narrow, and it is only compatible with a few polar solvents (such as methanol and acetonitrile). There is basically no signal for compounds with lower polarity, and compounds with lower polarity or poor solubility in polar solvents cannot be successfully ionized. Summary of the invention

[0007] In view of the above problems existing in the prior art, the object of the present invention is to provide an ion-induced spray ionization method and device.

[0008] To achieve the above object, the present invention adopts the following technical solution:

[0009] An ion-induced spray ionization method is to first use high pressure to make the auxiliary solvent produce charged induced ions, and then make the induced ions exchange charges with the sample in the capillary to ionize the sample.

[0010] As a preferred embodiment, the ion-induced spray ionization method comprises the following steps:

[0011] a) introducing the sample into the capillary;

[0012] b) introducing an auxiliary solvent into the auxiliary solvent channel, and applying high voltage through a high voltage generating device to cause the auxiliary solvent to generate charged induced ions;

[0013] c) The induced ions are transferred to the capillary to exchange charges with the sample, ionizing the sample.

[0014] As a further preferred embodiment, the high voltage applied by the high voltage generating device is a voltage of 1000 to 6000V.

[0015] An ion induced spray ionization device comprises an induced ion generating device, a capillary and a mass spectrometry injection channel. The induced ion generating device comprises an auxiliary solvent channel for introducing an auxiliary solvent, the auxiliary solvent channel is connected to a high voltage generating device, the outlet end of the auxiliary solvent channel is communicated with the end of the capillary, the tip of the capillary is located on the axis of the mass spectrometry injection channel, and the capillary is non-conductive.

[0016] As a preferred solution, the voltage provided by the high voltage generating device is 1000-6000V.

[0017] As a further preferred solution, the high voltage generating device is an induction voltage generating device.

[0018] As a preferred solution, a conductive metal foil is fixed to the outside of the auxiliary solvent channel, and the high voltage generating device is connected to the auxiliary solvent channel through the conductive metal foil.

[0019] As a preferred embodiment, the auxiliary solvent in the auxiliary solvent channel is a polar or non-polar solvent, the polar solvent includes but is not limited to methanol and acetonitrile, and the non-polar solvent includes but is not limited to dichloromethane and toluene.

[0020] As a preferred embodiment, the flow rate of the auxiliary solvent in the auxiliary solvent channel is 0.1 to 3 μl / min.

[0021] As a preferred solution, the auxiliary solvent channel is made of an insulating material, which includes but is not limited to glass and peek.

[0022] As a preferred solution, the axis of the capillary and the axis of the mass spectrometer injection channel are on the same horizontal line.

[0023] As a preferred solution, the axis of the auxiliary solvent channel is on the same horizontal line as the axis of the capillary.

[0024] As a preferred solution, the distance between the tip outlet of the capillary and the port of the mass spectrometer injection channel is 1 to 15 mm.

[0025] As a preferred solution, the diameter of the tip outlet of the capillary is 1 to 20 microns.

[0026] As a preferred solution, the induced ion generating device comprises an auxiliary electrode, and the auxiliary electrode is arranged in the auxiliary solvent channel.

[0027] As a further preferred embodiment, the auxiliary electrode is a conductor or a semiconductor.

[0028] As a further preferred solution, the auxiliary electrode is detachable.

[0029] As a preferred solution, the outer sleeve of the capillary is provided with a capillary fixing device.

[0030] As a preferred solution, it further comprises a sample introduction channel, wherein the sample introduction channel is communicated with the end of the capillary tube.

[0031] As a further preferred embodiment, the liquid flow rate of the sample introduction channel is 50 nanoliters to 5 microliters per minute.

[0032] As a further preferred solution, it also includes a three-way fixing device, in which the auxiliary solvent channel, the capillary tube, and the sample introduction channel are respectively fixed.

[0033] Compared with the prior art, the beneficial technical effects of the present invention are:

[0034] The present invention creatively utilizes charged induced ions generated by high-voltage ionization auxiliary solvents to exchange charges with samples, thereby ionizing the samples. The method is not only easy to implement, simple to operate, and low in cost, but can also effectively solve the problems of easy in-source oxidation of samples and poor compatibility of ionized solvents in traditional ESI. The method has a good ionization effect on compounds with low polarity and compounds that are prone to redox reactions, and has good compatibility with ionized solvents. The method has low selectivity for samples to be tested, sample solvents, and auxiliary solvents, and can test a wide range of sample objects, sample solvents, and auxiliary solvents. The method can be used for trace analysis and detection, has strong applicability, and is a significant improvement over the prior art. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 A schematic diagram of the structure of the ion-induced spray ionization device provided by the present invention;

[0036] Figure 2 for Figure 1 A schematic diagram of the structure when the ionization device is provided with an auxiliary electrode;

[0037] Figure 3 for Figure 1 A schematic diagram of the structure of the ionization device when it is provided with a sample introduction channel and a three-way fixing device;

[0038] Figure 4 for Figure 1 A schematic diagram of the structure of the ionization device when it is provided with an auxiliary electrode, a sample introduction channel and a three-way fixing device;

[0039] Figure 5 This is a mass spectrum analysis diagram of a 100 ppm diquat sample obtained by using the ion-induced spray ionization device of the present invention in Invention Example 1;

[0040] Figure 6 This is a mass spectrum analysis diagram of a 100 ppm diquat sample obtained by Nano-ESI in Example 1 of the present invention;

[0041] Figure 7 This is a mass spectrum analysis diagram of a 100 ppm diquat sample obtained by ESI in Example 1 of the present invention;

[0042] Figure 8 This is a mass spectrum analysis diagram of a 10 ppm anthracene sample obtained by using the ion-induced spray ionization device of the present invention in Example 2 of the present invention;

[0043] Fig. 9 This is a mass spectrum analysis diagram of a 10 ppm anthracene sample obtained by Nano-ESI in Example 2 of the present invention;

[0044] Fig.10 This is a mass spectrum analysis diagram of a 10 ppm anthracene sample obtained by ESI in Example 2 of the present invention;

[0045] Fig.11 This is a mass spectrometry analysis diagram of a p1-level single Hela cell methanol extract obtained by using the ion-induced spray ionization device of the present invention in Example 3 of the present invention;

[0046] Fig.12 This is a mass spectrometry analysis diagram of a single Hela cell dichloromethane extract obtained by using the ion-induced spray ionization device of the present invention in Example 4 of the present invention;

[0047] Fig.13 This is a mass spectrometry analysis of a single Hela cell dichloromethane extract obtained by Nano-ESI in Example 4 of the present invention;

[0048] The numbers in the figure are as follows: 1. Induced ion generating device; 11. Auxiliary solvent channel; 12. High voltage generating device; 13. Conductive metal foil; 14. Auxiliary electrode; 2. Capillary; 3. Mass spectrometry injection channel; 4. Capillary fixing device; 5. Sample introduction channel; 6. Tee; 7. Tee tight joint. DETAILED DESCRIPTION

[0049] The technical solution of the present invention is further described in detail and completely below in conjunction with the accompanying drawings.

[0050] like Figures 1 to 4 As shown: An ion induced spray ionization device provided by the present invention includes an induced ion generating device 1, a capillary 2 and a mass spectrometer injection channel 3, the induced ion generating device 1 includes an auxiliary solvent channel 11 for introducing an auxiliary solvent, the auxiliary solvent channel 11 is connected to a high voltage generating device 12, the outlet end of the auxiliary solvent channel 11 is communicated with the end of the capillary 2, the tip of the capillary 2 is located on the axis of the mass spectrometer injection channel 3, and the capillary 2 is non-conductive.

[0051] The ionization device described in the present invention is compatible with common mass spectrometers (such as triple quadrupole mass spectrometer, time-of-flight mass spectrometer, ion trap mass spectrometer, Fourier transform ion cyclotron resonance, etc.), and can also be extended to other mass spectrometry analyses. When used for mass spectrometry analysis, it can be used in conjunction with a common mass spectrometer, and has a wide range of applications and strong practicality.

[0052] The method for achieving ionization using the ion-induced spray ionization device of the present invention is to first generate charged induced ions in the auxiliary solvent by high pressure, and then allow the induced ions to exchange charges with the sample in the capillary to ionize the sample. Specifically, the method includes the following steps:

[0053] a) introducing a sample into capillary 2;

[0054] b) introducing the auxiliary solvent into the auxiliary solvent channel 11, and applying high voltage through the high voltage generating device 12 to make the auxiliary solvent generate charged induced ions;

[0055] c) The induced ions are transferred to the capillary 2 to exchange charges with the sample, thereby ionizing the sample.

[0056] As can be seen from the above, the ion-induced spray ionization device described in the present application adopts a non-contact high-voltage design, that is, the sample is separated from the high voltage, and the sample is not ionized by directly ionizing the sample using the high voltage. Instead, the high voltage ionization auxiliary solvent is first used to generate charged induced ions, and then the induced ions are used to exchange charges with the sample to ionize the sample, thereby effectively inhibiting the in-source oxidation of the sample, and minimizing the occurrence of redox reactions of the sample to be tested, so that the ionization device also has a good ionization effect on samples that are prone to redox. In addition, because the present invention ionizes the sample by induced ions, the ionization solvent has good compatibility, low selectivity for samples and sample solvents, and a wide range of compatible samples and sample solvents. The sample can be a compound with low polarity or high polarity, and the sample solvent can flexibly select polar or non-polar solvents, thereby making the ionization device It also has a good ionization effect on compounds with low polarity or poor solubility in polar solvents; in addition, since the auxiliary solvent and the sample are not ionized by high pressure at the same time, the selectivity for the auxiliary solvent is low, the range of compatible auxiliary solvents is large, and the auxiliary solvent can flexibly select polar or non-polar solvents (the polar solvents include but are not limited to methanol and acetonitrile, and the non-polar solvents include but are not limited to dichloromethane and toluene); in addition, the induced ions induced by high pressure are transferred to the capillary 2 to exchange charges with the sample to ionize the sample, so that the ionized sample can be sprayed out from the tip of the capillary 2 in an atomized state without auxiliary gases such as nitrogen and enter the subsequent mass spectrometry injection channel 3 for mass spectrometry analysis, which is low-cost and easy to implement, and the setting of the capillary 2 makes the ionization device consume little sample, and only a few pl of sample volume is required at the minimum, which can be suitable for trace analysis and detection work.

[0057] In the present application, the voltage provided by the high voltage generator 12 is 1000-6000 V. The high voltage generator 12 is an induction voltage generator, which generates an induction voltage of 1000-6000 V. Compared with conventional high voltage, the induction voltage can better reduce the occurrence of sample redox, and further enhance the ionization effect of the ionization device on unstable samples that are prone to redox.

[0058] See also Figures 1 to 4 As shown:

[0059] A conductive metal foil 13 is fixed to the outside of the auxiliary solvent channel 11, and the high voltage generating device 12 is connected to the auxiliary solvent channel 11 through the conductive metal foil 13, which enhances the conductivity of the high voltage and further enhances the induction effect of the high voltage on the auxiliary solvent. Specifically, the conductive metal foil 13 is fixed to the outside of the auxiliary solvent channel 11 by wrapping.

[0060] The flow rate of the auxiliary solvent in the auxiliary solvent channel 11 is 0.1 to 3 μl / min.

[0061] The material of the auxiliary solvent channel 11 can be an insulating material or a non-insulating material. In the present application, the material of the auxiliary solvent channel 11 is an insulating material, and the insulating material includes but is not limited to glass and peek, so as to further ensure the effect of the non-contact high-voltage design.

[0062] The axis of the capillary 2 is on the same horizontal line as the axis of the mass spectrometer injection channel 3, and the axis of the auxiliary solvent channel 11 is on the same horizontal line as the axis of the capillary 2, so as to induce ions to enter the capillary 2 to exchange charges with the sample to ionize the sample and facilitate the ionized sample to enter the mass spectrometer injection channel 3 for subsequent mass spectrometer analysis.

[0063] The distance d between the tip outlet of the capillary 2 and the port of the mass spectrometer injection channel 3 is preferably 1 to 15 mm. Since the high-voltage generator 12 is disposed in the auxiliary solvent channel 11, the distance between the high voltage and the mass spectrometer injection channel 3 can be larger, which has less impact on the mass spectrometer and further ensures the mass spectrometer analysis effect.

[0064] The diameter of the tip outlet of the capillary 2 is 1 to 20 microns. In the present application, the front end of the capillary 2 is designed as a tip, which can ensure the atomization effect of the sample, so as to generate sample spray and make the ionized sample spray out of the capillary 2 in an atomized state.

[0065] The outer sleeve of the capillary 2 is provided with a capillary fixing device 4 for fixing the capillary 2, thereby ensuring the stability of the entire device.

[0066] See also Figure 2 and Figure 4As shown, the induced ion generating device 1 includes an auxiliary electrode 14, and the auxiliary electrode 14 is arranged in the auxiliary solvent channel 11. The auxiliary electrode 14 can cooperate with high voltage to assist in induced ion generation, further improving the ionization effect. The auxiliary electrode 14 is a conductor or a semiconductor. Among them, the conductor can be a thin steel needle, and the semiconductor can be a carbon fiber. In the present application, the auxiliary electrode 14 is detachable and can be removed from the auxiliary solvent channel 11, and whether to use the auxiliary electrode 14 can be selected as needed.

[0067] In the present application, the sample solution can be directly sucked by the capillary 2, or the sample solution can be introduced into the capillary 2 (specifically, introduced into the tip of the capillary) by other means, see Figure 3 and Figure 4 As shown, the ionization device also includes a sample introduction channel 5, and the sample introduction channel 5 is connected to the end of the capillary 2. When ionization is performed, the sample solution can be introduced into the capillary 2 through the sample introduction channel 5. The flow rate of the liquid (i.e., the sample solution) in the sample introduction channel 5 is 50 nanoliters to 5 microliters per minute. In actual use, the sample introduction channel 5 can be externally connected to an injection device (not shown), and the injection device includes but is not limited to liquid chromatography, gas chromatography, injection pump, capillary electrophoresis and other continuous injection devices, so that the ionization device can be continuously injected and the signal is stable. In the present application, the sample introduction channel 5 can be a peek tube. In order to make the ionization device have better balance and stability, the ionization device also includes a three-way fixing device, and the auxiliary solvent channel 11, the capillary 2, and the sample introduction channel 5 are respectively fixed in the three-way fixing device. The three-way fixing device can be a general fixing device. For example, in the present application, the three-way fixing device includes a tee 6 (which can be a liquid phase tee) and a three-way tight joint 7. The auxiliary solvent channel 11, the capillary 2, and the sample introduction channel 5 are respectively fixed in three different channels of the tee 6. The tee 6 is used to fix and connect the auxiliary solvent channel 11, the capillary 2, and the sample introduction channel 5. The three-way tight joint 7 is used to ensure the liquid tightness of the entire device. In the present application, the material of the tee 6 and the three-way tight joint 7 is peek.

[0068] The technical effects that can be achieved by the present invention are further explained below in conjunction with specific application examples.

[0069] Example 1

[0070] The ion-induced spray ionization device and the mass spectrometer (the mass analyzer is a triple quadrupole) of the present invention are used to treat diquat (CAS.2764-72-9) which is prone to redox reaction and unstable: Perform mass spectrometry analysis:

[0071] Experimental setup Figure 3 shown.

[0072] Methanol is used as a sample solvent, diquat is dissolved in methanol to prepare a 100 ppm sample solution, and the sample solution is introduced into the capillary 2 through the sample introduction channel 5, the flow rate of the sample solution in the sample introduction channel 5 is 5 microliters / minute, and the distance d between the tip outlet of the capillary 2 and the port of the mass spectrometer injection channel 3 is 5 mm; methanol is used as an auxiliary solvent, and methanol is introduced into the auxiliary solvent channel 11, and the flow rate of methanol is 2 microliters / minute. The high-voltage generator 12 is connected, and a high voltage of 2500V is applied through the high-voltage generator 12, and the high voltage ionizes the methanol, so that the methanol generates charged induced ions; the induced ions are transferred to the capillary 2 to exchange charges with the sample, so that the sample is ionized; the sample ions enter the mass spectrometer through the mass spectrometer injection channel 3 to perform subsequent mass spectrometry analysis, and the analysis results are as follows Figure 5 In addition, under the same conditions, conventional Nano-ESI and ESI with mass spectrometer (mass analyzer is triple quadrupole) were used to perform mass spectrometry analysis on diquat, and the analysis results are shown in Figure 6 and Figure 7 shown.

[0073] Figure 5 This is a mass spectrometry analysis diagram (positive ion mode) of a 100 ppm diquat sample obtained using the ion-induced spray ionization device of the present invention in this example; Figure 6 This is the mass spectrum analysis diagram of the 100 ppm diquat sample obtained by Nano-ESI in this example (positive ion mode); Figure 7 : is the mass spectrometry analysis diagram of the 100 ppm diquat sample obtained by ESI in this example (positive ion mode); Figure 5 It can be seen that in addition to the ion peak (m / z92) related to the compound, there is no interference from other impurity ion peaks in the spectrum, the spectrum is easy to interpret, and there is no Figure 6 and Figure 7 The interfering ion peaks (m / z 157, 183) are caused by the redox reactions of the samples to varying degrees, indicating that the ion-induced spray ionization method and device of the present invention can effectively reduce the redox reactions of the compounds, and can achieve good ionization effects on unstable compounds that are prone to redox reactions.

[0074] Example 2

[0075] The ion-induced spray ionization device and the mass spectrometer (the mass analyzer is a triple quadrupole) of the present invention are used to analyze anthracene with low polarity: Perform mass spectrometry analysis:

[0076] Experimental setup Figure 4 shown.

[0077] Toluene is used as a sample solvent, anthracene is dissolved in toluene, and a 10 ppm sample solution is prepared. The sample solution is introduced into the capillary 2 through the sample introduction channel 5, and the flow rate of the sample solution in the sample introduction channel 5 is 5 μL / min. The distance d between the tip outlet of the capillary 2 and the port of the mass spectrometer injection channel 3 is 5 mm. Toluene is used as an auxiliary solvent, and toluene is introduced into the auxiliary solvent channel 11, and the flow rate of toluene is 2 μL / min. The high-voltage generator 12 is turned on, and a high voltage of 2500V is applied through the high-voltage generator 12. At the same time, the auxiliary electrode 14 (carbon fiber) is used to make the toluene generate charged induced ions; the induced ions are transferred to the capillary 2 to exchange charges with the sample to ionize the sample; the sample ions enter the mass spectrometer through the mass spectrometer injection channel 3 to perform subsequent mass spectrometry analysis, and the analysis results are shown as follows: Figure 8 In addition, under the same conditions, conventional Nano-ESI and ESI with mass spectrometer (mass analyzer is triple quadrupole) were used to perform mass spectrometry analysis on anthracene. The analysis results are shown in Fig. 9 and Fig.10 shown.

[0078] Figure 8 This is a mass spectrometry analysis diagram (positive ion mode) of a 10 ppm anthracene sample obtained using the ion-induced spray ionization device of the present invention in this example; Fig. 9 This is the mass spectrometry analysis of a 10 ppm anthracene sample obtained using Nano-ESI in this example (positive ion mode); Fig.10 : is the mass spectrum analysis diagram (positive ion mode) of the 10 ppm anthracene sample obtained by ESI in this example; Figure 8 It can be seen that in the spectrum, except for the ion peak (m / z179) related to the compound, there is no interference from other impurity ion peaks, and the spectrum is easy to interpret; Fig. 9 and Fig.10 No effective signal was detected in the results, indicating that the ion-induced spray ionization method and device of the present invention can achieve good ionization effect for compounds with lower polarity.

[0079] Example 3

[0080] The ion-induced spray ionization device and mass spectrometer (mass analyzer is Q-TOF) of the present invention are used to perform mass spectrometry analysis on the methanol extract of a single Hela cell:

[0081] Experimental setup Figure 1 shown.

[0082] With methanol as the sample solvent, Hela cells were cultured in a 60mm standard cell culture dish according to the conventional cell biology culture process. 15pl of methanol was pre-filled into the capillary 2, and the Hela cells were pierced under the control of the three-dimensional mobile platform to extract the Hela cells to obtain a single Hela cell methanol extract (sample solution). Then the capillary 2 was fixed, and the distance d between the tip outlet of the capillary 2 and the port of the mass spectrometry injection channel 3 was 3mm; with methanol as the auxiliary solvent, methanol was introduced into the auxiliary solvent channel 11, and the flow rate of methanol was 0.5 microliters / minute. The high-voltage generator 12 was turned on, and a high voltage of 2000V was applied through the high-voltage generator 12. The high voltage ionized methanol to generate charged induced ions in the methanol; the induced ions were transferred to the capillary 2 to exchange charges with the sample to ionize the sample; the sample ions entered the mass spectrometer through the mass spectrometry injection channel 3 to perform subsequent mass spectrometry analysis, and the analysis results are shown as follows: Fig.11 shown.

[0083] Fig.11 : is a mass spectrometry analysis diagram (positive ion mode) of a p1-level single Hela cell methanol extract obtained by using the ion-induced spray ionization device of the present invention in the example; Fig.11 It can be seen that many peaks of cell metabolites appear in the spectrum, especially at m / z 600-900, where a very high signal appears, which is mainly the phospholipid component in Hela cells, indicating that the ion-induced spray ionization method and device described in the present invention can be used to monitor and analyze trace samples.

[0084] Example 4

[0085] The ion-induced spray ionization device and mass spectrometer (mass analyzer is Q-TOF) of the present invention are used to perform mass spectrometry analysis on the dichloromethane extract of a single Hela cell:

[0086] Experimental setup Figure 2 shown.

[0087] Using dichloromethane as the sample solvent, Hela cells were cultured in a 60mm standard cell culture dish according to the conventional cell biology culture process. The capillary was pre-filled with 15pl of dichloromethane, and the Hela cells were pierced under the control of the three-dimensional mobile platform to extract the Hela cells to obtain a single Hela cell dichloromethane extract (sample solution). Then the capillary 2 was fixed, and the distance d between the tip outlet of the capillary 2 and the port of the mass spectrometry injection channel 3 was 3mm; using dichloromethane as the auxiliary solvent, dichloromethane was introduced into the auxiliary solvent channel 11, and the flow rate of dichloromethane was 0.5 microliters / minute. The high-voltage generator 12 was turned on, and a high voltage of 2000V was applied through the high-voltage generator 12. At the same time, the auxiliary electrode 14 (carbon fiber) was used to make the dichloromethane generate charged induced ions; the induced ions were transferred to the capillary 2 to exchange charges with the sample to ionize the sample; the sample ions entered the mass spectrometer through the mass spectrometry injection channel 3 to perform subsequent mass spectrometry analysis, and the analysis results are shown as follows Fig.12 In addition, under the same conditions, the conventional Nano-ESI and mass spectrometer (mass analyzer is Q-TOF) were used to perform mass spectrometry analysis on the dichloromethane extract of a single Hela cell. The analysis results are shown in Fig.13 shown.

[0088] Fig.12 This is a mass spectrometry analysis diagram (positive ion mode) of a single Hela cell dichloromethane extract obtained by using the ion-induced spray ionization device of the present invention in the example; Fig.13 : is the mass spectrometry analysis diagram (positive ion mode) of the dichloromethane extract of a single Hela cell obtained by Nano-ESI in the example; Fig.12 It can be seen that the spectrum shows a high signal of phospholipids in Hela cells at m / z 600-900, and Fig.13 There was no signal peak of cholesterol (m / z 369) detected in Fig.13 The effective signal peaks obtained are relatively few and the spectrum is relatively complex, indicating that the ion-induced spray ionization method and device described in the present invention can be compatible with a wide range of solvent polarities.

[0089] In summary, the ion-induced spray ionization method and device of the present invention can effectively solve the problems of easy in-source oxidation of samples and poor compatibility of ionized solvents in traditional ESI, and has a good ionization effect on compounds with low polarity and compounds that are easy to undergo redox reactions; it has good compatibility with ionized solvents, so the selectivity for samples to be tested, sample solvents, and auxiliary solvents is low, and a wide range of sample objects, sample solvents, and auxiliary solvents can be tested; in addition, it can be used not only for conventional analysis and detection, but also for trace analysis and detection, with strong applicability, and compared with the existing technology, it has significant progress and practical value.

[0090] Finally, it is necessary to point out here that the above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto, and any changes or substitutions that can be easily thought of by any technician familiar with the technical field within the technical scope disclosed by the present invention should be covered within the protection scope of the present invention.

Claims

1. An ion-induced spray ionization method, characterized in that: An ion-induced spray ionization device is used to ionize the sample. The ion-induced spray ionization device includes an induced ion generating device, a capillary and a mass spectrometry injection channel. The induced ion generating device includes an auxiliary solvent channel for introducing an auxiliary solvent. The auxiliary solvent channel is connected to a high-voltage generating device. The outlet end of the auxiliary solvent channel is connected to the end of the capillary. The tip of the capillary is located on the axis of the mass spectrometry injection channel. The capillary is non-conductive. The axis of the capillary is on the same horizontal line as the axis of the mass spectrometry injection channel. The axis of the auxiliary solvent channel is on the same horizontal line as the axis of the capillary. The material of the auxiliary solvent channel is an insulating material. The ion-induced spray ionization method comprises the following steps: a) introducing the sample into the capillary; b) introducing an auxiliary solvent into the auxiliary solvent channel, and applying high voltage through a high voltage generating device to cause the auxiliary solvent to generate charged induced ions; c) The induced ions are transferred to the capillary to exchange charges with the sample, ionizing the sample.

2. The ion-induced spray ionization method according to claim 1, characterized in that: The voltage provided by the high voltage generating device is 1000-6000V.

3. The ion-induced spray ionization method according to claim 1, characterized in that: A conductive metal foil is fixed to the outside of the auxiliary solvent channel, and the high voltage generating device is connected to the auxiliary solvent channel through the conductive metal foil.

4. The ion-induced spray ionization method according to claim 1, characterized in that: The distance between the tip outlet of the capillary and the port of the mass spectrometer injection channel is 1 to 15 mm.

5. The ion-induced spray ionization method according to claim 1, characterized in that: The induced ion generating device comprises an auxiliary electrode, and the auxiliary electrode is arranged in the auxiliary solvent channel.

6. The ion-induced spray ionization method according to claim 5, characterized in that: The auxiliary electrode is detachable.

7. The ion-induced spray ionization method according to claim 1, characterized in that: The outer sleeve of the capillary is provided with a capillary fixing device.

8. The ion-induced spray ionization method according to claim 1, characterized in that: The invention also comprises a sample introduction channel, wherein the sample introduction channel is communicated with the end of the capillary tube.

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