A capillary electrospray ion source device and mass spectrometer thereof

Abstract

This invention provides a capillary electrospray ionization source device, comprising a housing with vertically connected sections. Inside the housing, from top to bottom, are sequentially arranged a vertically movable pressing sleeve, a conical electrode, and a clamp. The pressing sleeve protrudes from the housing and contains a sampling capillary. The bottom of the pressing sleeve is connected to the conical electrode, and the sampling capillary abuts against the upper end of the conical electrode. The conical electrode has a conical hole, and a spray capillary is embedded in the lower end of the sampling capillary. The spray capillary passes through the conical hole of the conical electrode, passes through the clamp, and is held by the clamp. The conical electrode is positioned on one end of the clamp, and the other end of the clamp has a gripper for holding the spray capillary. Both the pressing sleeve and the clamp are equipped with spring-loaded components. This invention utilizes capillary action to achieve integrated operation of spontaneous sample collection, sample transfer, and ionization, with a simple structure and easy operation.

Description

Technical Field

[0001] This invention relates to the field of mass spectrometry detection and analysis technology, and more specifically, to a capillary electrospray ionization source device and its mass spectrometer. Background Technology

[0002] Ion sources are an essential component of mass spectrometry instruments. Their main function is to ionize analytes using physical and chemical principles such as light, heat, and electricity, through physical or chemical reactions, allowing the analytes to enter the mass analyzer for subsequent separation, detection, and other operations. The development of ion sources has driven the development of mass spectrometry, while the development of mass spectrometry has also placed new demands on ion sources.

[0003] Electrospray ionization (ESI) is one of the most widely used ion sources, enabling the ionization analysis of non-volatile samples. As a soft ionization technique that does not generate molecular debris, ESI can directly determine thermally unstable compounds and generate multi-charged ions, offering unique advantages in metabolomics, proteomics, and other research fields. However, traditional commercial ESI sources are typically large, complex, and expensive, requiring additional gas cylinders and heating devices to provide nebulization aids to improve desolvation and ionization efficiency. These factors significantly limit the coupling of ESI with small mass spectrometers and its application in rapid detection. Furthermore, the relatively high spray flow rate of traditional ESI also results in typically low ionization efficiency.

[0004] Nano-ESI (nano-electrospray ionization) is a mass spectrometry technique developed after ESI. It improves ionization efficiency by reducing the spray flow rate and has a simpler structure, eliminating the need for auxiliary equipment such as high-temperature carrier gases. However, despite these advantages, the spray tip (inner diameter ~μm) of Nano-ESI typically requires a specialized capillary puller for shaping, resulting in high equipment costs. Furthermore, due to its extremely small pore size, the tip of Nano-ESI is highly susceptible to damage and clogging, affecting normal sample analysis.

[0005] Therefore, it is necessary to develop a highly sensitive electrospray ion source that is simple in structure, compact, portable, and inexpensive based on the principle of electrospray ionization, so as to enable its use in conjunction with different mass spectrometry instruments, especially small mass spectrometers, for rapid analysis in different scenarios. Summary of the Invention

[0006] To address the aforementioned problems, this invention provides a capillary electrospray ionization source device. This device is simple in structure and low in cost, while achieving integrated operation of spontaneous sample collection, sample transfer and ionization. It can be coupled and used with a variety of mass spectrometry instruments, including miniature mass spectrometers.

[0007] Another object of the present invention is to provide a mass spectrometer comprising the capillary electrospray ion source device.

[0008] To achieve the above-mentioned technical objectives, the capillary electrospray ion source device of the present invention includes a housing with vertically connected sections. Inside the housing, from top to bottom, are sequentially arranged a vertically movable pressing sleeve, a conical electrode, and a clamp. The pressing sleeve protrudes outside the housing and contains a sampling capillary. The bottom of the pressing sleeve is connected to the conical electrode, and the sampling capillary abuts against the upper end of the conical electrode. The conical electrode has a conical hole, and a spray capillary is embedded in the lower end of the sampling capillary. The spray capillary passes through the conical electrode... The conical hole passes through the clamp and is held by the clamp. The conical electrode is placed on one end of the clamp, and the other end of the clamp has a claw for holding the spray capillary. The pressing sleeve and the clamp are both provided with a spring-loaded element. When the pressing sleeve is pressed, the pressing sleeve presses the conical electrode and pushes the clamp to release the spray capillary. When the pressing sleeve is released, the pressing sleeve, the conical electrode, and the clamp are reset under the action of the spring-loaded element, and clamp the spray capillary.

[0009] Furthermore, the spring-loaded component of the pressing sleeve includes a spring and a spring-loaded limiter. The spring-loaded limiter is formed by a protrusion on the outer wall of the pressing sleeve matching the shoulder step surface of the inner wall cavity of the housing. The spring is sleeved between the protrusion on the outer wall of the pressing sleeve and the conical electrode.

[0010] Furthermore, the clamp is used to fix and replace the spray capillary. Specifically, the clamp includes a clamping rod for housing the spray capillary and a spring-loaded component. One end of the clamping rod is connected to the conical electrode, and the other end of the clamping rod is provided with a jaw. The spring-loaded component includes a protrusion on the outer wall of the clamping rod, a fixing member, and a spring sleeved between the protrusion on the outer wall of the clamping rod and the fixing member. The fixing member is fixed in the cavity at one end of the housing and sleeved on the end of the clamping rod with the jaw, forming a cavity between the fixing member and the clamping rod that allows the clamping rod to move up and down. When the clamping rod moves downward, the jaw disengages from the fixing member, releasing the clamped spray capillary. When the clamping rod returns to its original position, the jaw retracts into the fixing member, clamping the spray capillary.

[0011] Furthermore, the housing can be integral or separate, which facilitates the replacement of the capillary tube. The housing includes an upper outer shell and a lower outer shell, which are connected by threads or by snap-fit.

[0012] Furthermore, the sampling capillary can be selected from any other material with an outer diameter of less than 2 mm and an inner diameter of greater than 590 μm for collection; preferably, it is a capillary from any other material with an outer diameter of 0.69-2 mm and an inner diameter of 590-1900 μm for collection.

[0013] Furthermore, the spray capillary can be a capillary with an outer diameter of 150-360 μm and an inner diameter greater than 50 μm, preferably with an inner diameter of 75-150 μm. Alternatively, a capillary with a suitable inner diameter can be selected based on the sample viscosity.

[0014] Furthermore, the upper end of the spray capillary is embedded 1-3 mm inside the sampling capillary.

[0015] Furthermore, the conical electrode is connected to an external power source, so that when power is applied, the sample solution is sprayed under the action of high voltage applied by the conical electrode, thus completing ionization.

[0016] In the technical solution of this invention, the sample solution is first drawn up by the capillary action of the sampling capillary, and then inserted into the device along the central hole of the pressing sleeve, and nested and coupled with the spray capillary. Afterwards, the sample solution is transferred from the sampling capillary to the spray capillary under capillary action, and is sprayed under the high pressure applied by the cone electrode, thus completing the ionization of the sample.

[0017] The present invention also provides a mass spectrometer comprising the capillary electrospray ionization source device.

[0018] The capillary electrospray ionization source device of this invention utilizes capillary action to achieve integrated operation of spontaneous sample collection, sample transfer and ionization. It eliminates the need for complex liquid flow pipelines and auxiliary equipment such as syringe pumps and pipettes, resulting in a simple structure and low cost. Moreover, the spray capillary does not undergo tipping treatment, making the structure robust and less prone to damage. It also facilitates convenient and rapid detection, significantly reducing system complexity and providing high ionization efficiency. This allows for the miniaturization of micro mass spectrometers while expanding their functionality, demonstrating strong application potential in the field of rapid on-site analysis. Attached Figure Description

[0019] Figure 1 This is a schematic diagram of the capillary electrospray ion source device described in this invention;

[0020] Figure 2 This is a schematic diagram of the holder in the loosened state of the capillary electrospray ion source device of the present invention;

[0021] Figure 3 The mass spectrum of a reserpine sample with a concentration of 1 μg / ml was collected using the capillary electrospray ionization source device described in this invention.

[0022] Figure 4This is a mass spectrometry stability test diagram of the capillary electrospray ion source device described in this invention;

[0023] Figure 5 This is a comparison chart of the ionization efficiency of the capillary electrospray ion source device and the nano-electrospray ion source described in this invention.

[0024] Figure 6 This is a secondary mass spectrum of an imatinib sample with a minimum detection limit concentration of 1 ng / ml, obtained by sensitivity testing of the capillary electrospray ion source device described in this invention.

[0025] Figure 7 The mass spectrum of a drug mixture extracted from the surface of a plastic-sealed bag was determined using the capillary electrospray ion source device described in this invention.

[0026] Figure 8a This is a graph showing the relationship between the blood concentration of the psychotropic drug clozapine and the ion signal intensity in whole blood using the capillary electrospray ion source device described in this invention.

[0027] Figure 8b This is a secondary mass spectrum of a clozapine sample with a minimum detection limit concentration of 10 ng / ml using the capillary electrospray ionization source device described in this invention.

[0028] The numbers on the map are:

[0029] 1. Sampling capillary tube; 2. Conical electrode; 3. Spray capillary tube; 4. Pressing sleeve; 5. Convex ring.

[0030] 5. Spring; 6. Clamp; 61. Spring II; 62. Clamping rod; 62. Clamping rod protrusion ring.

[0031] 63. Fastener; 64. Clamp; 7. Upper outer shell; 71. Shoulder step surface; 8. Lower outer shell.

[0032] 81. Stepped surface; 9. Cavity Detailed Implementation

[0033] To make the objectives, technical solutions, and advantages of the present invention clearer, the technical solutions of exemplary embodiments of the present invention are described below in conjunction with the accompanying drawings. Elements and features described in one drawing or embodiment of the present invention may be combined with elements and features shown in one or more other drawings or embodiments. It should be noted that, for clarity, representations and descriptions of components or processes unrelated to the present invention and known to those skilled in the art have been omitted from the drawings and description.

[0034] The present invention will now be further described with reference to the accompanying drawings.

[0035] like Figure 1 and Figure 2As shown, this embodiment of the invention provides a capillary electrospray ionization source device, including a shell with vertically connected housing. Inside the shell, from top to bottom, are a vertically movable pressing sleeve 4, a conical electrode 2, and a clamp 6. The pressing sleeve 4 protrudes outside the shell and contains a sampling capillary 1. The bottom of the pressing sleeve 4 is connected to the conical electrode 2. The sampling capillary 1 abuts against the upper end of the conical electrode 2. The conical electrode 2 has a conical hole. A spray capillary 3 is embedded in the lower end of the sampling capillary 1. The spray capillary 3 passes through the conical hole of the conical electrode 2 and through the clamp 6, and is clamped by the clamp 6. The conical electrode 2 is placed on one end of the clamp 6. The other end of the clamp 6 has a gripper 64 for clamping the spray capillary 3. Both the pressing sleeve 4 and the clamp 6 have spring-loaded components. When the pressing sleeve 4 is pressed, the pressing sleeve 4 presses the conical electrode 2 and pushes the clamp 6 to release the spray capillary 3 (e.g., ...). Figure 2 (As shown); when the pressing sleeve 4 is released, the pressing sleeve 4, the cone electrode 2, and the clamp 6 are reset under the action of the spring-loaded component, clamping the spray capillary 3.

[0036] The housing of the capillary spray ion source device in this embodiment can be integrated or separate. Separate housings are more convenient for replacing the capillary. For example, the housing includes an upper outer shell 7 and a lower outer shell 8, which are connected by threads or by snap-fit.

[0037] As shown in the figure, the spray capillary holder 6 is placed inside the lower outer shell 8, and the pressing sleeve 4 is placed inside the upper outer shell 7. A snap fastener is provided between the lower outer shell 8 and the upper outer shell 7 for connection.

[0038] The pressing sleeve 4 has a central hole for placing the sampling capillary tube 1; the spring-loaded component of the pressing sleeve 4 includes a spring 5 and a spring-loaded limiter. The spring-loaded limiter is formed by matching the convex shape (such as a convex ring 41) on the outer wall of the pressing sleeve 4 with the shoulder step surface 71 of the inner wall cavity of the upper housing 7. The spring 5 is sleeved between the convex ring 41 on the outer wall of the pressing sleeve 4 and the conical electrode 2.

[0039] The clamp 6 has a through hole for fixing and replacing the spray capillary 3. The structure can be varied. For example, the clamp 6 includes a clamping rod 62 that can house the spray capillary 3, and a spring-loaded component of the clamp. One end of the clamping rod 62 is connected to the conical electrode 2, and the other end of the clamping rod 62 is provided with a jaw 64. The spring-loaded component of the clamp 6 includes a protrusion on the outer wall of the clamping rod 62 (such as a clamping rod protrusion ring 621), a fixing member 63, and a spring 61 between the clamping rod protrusion ring 621 and the fixing member 63 on the outer wall of the clamping rod 62. The fixing member 63 is fixed in the cavity at one end of the lower housing 8 and is sleeved on the end of the clamping rod 62 with the jaw 64. A cavity 9 is formed between the clamping rod 62 and the clamping rod 62, allowing the clamping rod to move up and down. When the clamping rod 62 moves downward, the jaw 64 disengages from the fixing member 63 and releases the clamped spray capillary 3. When the clamping rod 62 resets, the jaw 64 retracts into the fixing member 63 and clamps the spray capillary 3.

[0040] The gripper 64 consists of several elastic claw segments, such as three or four segments.

[0041] A retaining ring is also provided between the gripper 64 and the fixing member 63. The retaining ring and the fixing member are interference-fitted, and the gripper 64 and the retaining ring can slide relative to each other to ensure that the gripper 64 opens and closes, and completes the action of clamping or releasing the spray capillary 3.

[0042] The fixing member 63 and the clamping rod 62 can extend out of the housing to facilitate the placement and removal of the spray capillary tube 3. In order to further protect the spray capillary tube 3, a capillary protective sleeve can be provided for the part of the spray capillary tube that is exposed outside the clamping claw 64. The capillary protective sleeve and the fixing member 63 can be connected by threads or sleeves.

[0043] The sampling capillary 1 used in this embodiment has the same diameter, thus exhibiting the same capillary action and enabling quantitative collection and analysis of the sample. The sampling capillary 1 can be any other material used for collection, with an outer diameter less than 2 mm and an inner diameter greater than 590 μm; preferably, it uses a capillary with an outer diameter of 0.69-2 mm and an inner diameter of 590-1900 μm. A suitable capillary specification can be selected according to actual needs.

[0044] The sampling capillary 1 can also be modified on its inner wall to achieve functions such as sample enrichment and selection, and further pretreatment of complex samples.

[0045] The spray capillary 3 used has an outer diameter of 150-360 μm and an inner diameter greater than 50 μm, preferably an inner diameter of 75-150 μm. Alternatively, a capillary with a suitable inner diameter can be selected based on the sample viscosity.

[0046] Of course, in an optional embodiment of the present invention, the adjustable clamp 6 of the spray capillary can be replaced with a clamp that can hold a smaller outer diameter, corresponding to the spray capillary 3 used.

[0047] The upper end of the spray capillary 3 is embedded 1 mm inside the sampling capillary 1. It can be adjusted between 1 and 3 mm according to the actual situation so that the spray capillary is nested in the sampling capillary.

[0048] The conical electrode 2 is connected to an external power supply. It is an integrated metal electrode with a small cone at the top of a cylinder. The conical shape facilitates energizing the solution. A conical hole is provided in the center for the spray capillary to pass through. A thread is also provided at the cylindrical end of the conical electrode 2, allowing an external screw to pass through the housing for power supply. After energization, the sample solution is sprayed under high voltage applied to the conical electrode 2, completing ionization.

[0049] In the technical solution of this invention, the sample solution is first drawn up by the capillary action of the sampling capillary 1, and then inserted into the device along the central hole of the pressing sleeve 4, nested and coupled with the spray capillary 3. Afterwards, the sample solution is transferred from the sampling capillary 1 to the spray capillary 3 under capillary action, and is sprayed under the high pressure applied to the conical electrode 2, completing the ionization of the sample. The end of the sampling capillary 1 abuts against the conical tip of the conical electrode 2. Due to the capillary action of the sampling capillary 1 on the solution, the solution will remain inside the sampling capillary 1 without external force. After the sampling capillary 1 and the spray capillary 3 are nested, the solution will directly enter the spray capillary 3 under the capillary force of the spray capillary 3. Under the action of the two capillaries, the liquid will not overflow.

[0050] In one specific embodiment of the present invention, a borosilicate capillary with an outer diameter of 1.5 mm and an inner diameter of 0.84 mm is used as the sampling capillary 1; a capillary with an outer diameter of 360 μm and an inner diameter of 100 μm is used as the spray capillary 3. The voltage applied to the conical electrode 2 is 2700 V. The position of the spray capillary 3 relative to the mass spectrometer inlet is approximately x = 2.3 mm and y = 1.6 mm directly in front of it (x is the horizontal distance and y is the vertical distance). In this embodiment of the present invention, the lower end of the spray capillary 3 is located directly in front of the mass spectrometer inlet. On the plane directly in front of the mass spectrometer inlet, with the mass spectrometer inlet as the origin, the coordinates of the lower end of the spray capillary 3 are approximately 2.3 mm and 1.6 mm. The inlet position has a constant temperature heating interface, which means that after the sample spray enters the mass spectrometer inlet capillary, there is a heating device inside the instrument to help with desolvation.

[0051] After conducting the experiment using the capillary electrospray ion source device of this embodiment, the used sampling capillary 1 and spray capillary 3 are taken out. When conducting the experiment again, the spray capillary to be used is first placed into the holder and exposed outside the cone electrode 2. Then, the sampling capillary 1, which has absorbed the sample solution, is inserted again along the center hole of the pressing sleeve 4 and nested with the spray capillary 3.

[0052] After an experiment is completed, the sampling capillary 1 used for the next experiment can be reinserted from the pressing sleeve 4, while the spray capillary 3 can be inserted backwards into the clamp 6 from the open end of the claw clamp 64.

[0053] The capillary electrospray ion source device provided in the embodiments of the present invention will be coupled with an existing small mass spectrometer (“brick” small mass spectrometer) for analysis and testing.

[0054] Experimental Example 1

[0055] First, a reserpine sample with a concentration of 1 μg / ml was directly aspirated using sampling capillary 1 and placed in the ion source device of this embodiment for testing. Sampling capillary 1 used a capillary with an outer diameter of 1.5 mm and an inner diameter of 0.84 mm, while spray capillary 3 used a capillary with an outer diameter of 360 μm and an inner diameter of 100 μm. The ionization voltage was set to 2700 V, supplied by the instrument's own high-voltage module. The sample injection time was set to 10 ms, the m / z detection range was 100-700 Da, the electrode voltage was 4000 V, and the detector voltage was -1100 V. The collected mass spectrum is shown below. Figure 3 As shown, the ion source device in this embodiment is convenient and quick to use, and can be well coupled with existing mass spectrometers (preferably small mass spectrometers).

[0056] Experimental Example 2

[0057] To test the stability of the capillary electrospray ionization source device of this embodiment, a 1 μg / ml MRFA sample was directly aspirated using sampling capillary 1 and placed in the ionization source device of this embodiment for testing. Sampling capillary 1 used a capillary with an outer diameter of 1.5 mm and an inner diameter of 0.84 mm, while spray capillary 3 used a capillary with an inner diameter of 360 μm and an outer diameter of 100 μm. The ionization voltage was set to 2700 V, supplied by the instrument's own high-voltage module. The sample introduction time was set to 10 ms, the m / z detection range was 100-700 Da, the electrode high voltage was 4000 V, and the detector high voltage was -1100 V. The complete signal intensity change of one sampling was recorded, and the mass spectrometry signal duration was approximately 8 minutes.

[0058] The change of mass spectrometry signal intensity with test time is as follows: Figure 4 As shown, the relative standard deviation (RSD) of the signal intensity is 7.9%, indicating good stability of the mass spectrometry signal.

[0059] Experimental Example 3

[0060] To characterize the ionization performance of the capillary electrospray ionization source device of this embodiment, this experiment used both a nano ion source and the capillary electrospray ionization source device of this embodiment to test a cytochrome c sample (MRFA) with a concentration of 500 μg / ml. The ionization voltage of the nano ion source was set to 1100 V, while the ionization voltage of the capillary electrospray ionization source device of this embodiment was set to 2700 V, supplied by the instrument's own high-voltage module. The sample injection time was set to 10 ms, the m / z detection range was 100-700 Da, the electrode voltage was 4000 V, and the detector voltage was -1100 V. The collected mass spectra are shown below. Figure 5 As shown, the signal strengths of the two are comparable, indicating that the capillary electrospray ion source device of the present invention can achieve the ionization efficiency of conventional ion sources.

[0061] Experiment Example 4

[0062] To test the sensitivity of this system, imatinib samples of different concentrations (1-1000 ng / ml) were directly aspirated using sampling capillary 1 and placed in the ion source device of this embodiment for testing. Sampling capillary 1 used a capillary with an outer diameter of 1.5 mm and an inner diameter of 0.84 mm, while spray capillary 3 used a capillary with an outer diameter of 360 μm and an inner diameter of 100 μm. The ionization voltage was set to 2700 V, supplied by the instrument's own high-voltage module. The sample injection time was set to 100 ms, the m / z detection range was 100-700 Da, the electrode voltage was 4000 V, and the detector voltage was -1100 V. By adjusting the AC signal, the target ions were first isolated, and then collision-induced dissociation (CID) was induced within the trap to generate fragment ions, obtaining the secondary mass spectrum of the sample, as shown below. Figure 6 As shown. Figure 6 The image shows the secondary mass spectrum of an imatinib sample with a limit of detection of 1 ng / ml. When the concentration range is 1-1000 ng / ml, the mass spectrum signal is linearly correlated with the sample concentration, with a correlation coefficient R0. 2 =0.9991, indicating good linearity and a detection limit of 1 ng / ml.

[0063] Experimental Example 5

[0064] The capillary electrospray ionization source device provided in this invention can directly analyze surface samples using the capillary action of the sampling capillary. Since drug residues may remain on the sealed plastic bags during transportation, monitoring the drug surface of the sealed bags is essential. A 10 μl sample of a mixed drug sample containing acetylmorphine (1 μg / ml), fentanyl (1 μg / ml), and heroin (1 μg / ml) is dropped onto the sealed plastic bag. After air-drying, 10 μl of methanol-water mixture (v:v) is added. Extraction was performed on a sealed plastic bag at a ratio of 1:1. After 10 seconds, the extract was directly aspirated using a sampling capillary and placed in the ion source device for testing. Sampling capillary 1 used a capillary with an outer diameter of 1.5 mm and an inner diameter of 0.84 mm, while spray capillary 3 used a capillary with an outer diameter of 360 μm and an inner diameter of 100 μm. The ionization voltage was set to 2700 V, supplied by the instrument's own high-voltage module. The sample injection time was set to 10 ms, the m / z detection range was 100-700 Da, the electrode voltage was 4000 V, and the detector voltage was -1100 V. The mass spectrum of the collected mixed sample is shown below. Figure 7 As shown.

[0065] Experimental Example 6

[0066] In another specific embodiment of the present invention, a borosilicate capillary with an outer diameter of 1.5 mm and an inner diameter of 0.84 mm is used as the sampling capillary 1; a capillary with an outer diameter of 360 μm and an inner diameter of 75 μm is used as the spray capillary 3. The applied spray voltage is approximately 3200 V. For blood drug concentration monitoring experiments, firstly, whole blood samples containing the psychotropic drug clozapine are extracted with ethyl acetate. 30 μl of ethyl acetate is added to 50 μl of whole blood samples containing different concentrations of clozapine for liquid-liquid extraction. After vortexing and mixing for four seconds, 15 μl of the supernatant ethyl acetate is aspirated, and 11 μl of ethanol is added to the ethyl acetate extract to form a spray. This sample is aspirated with the sampling capillary for testing. The ionization voltage is set to 2700 V, supplied by the instrument's own high-voltage module. The sample injection time is set to 100 ms, the m / z detection range is 100-700 Da, the electrode high voltage is 4000 V, and the detector high voltage is -1100 V. By adjusting the AC signal, the target ion is first isolated, and then the target ion is caused to undergo collision-induced dissociation (CID) in the trap to generate fragment ions, thus obtaining the secondary mass spectrum of the sample, as shown in Figure 8.

[0067] The measured clozapine blood concentration showed a linear relationship with the signal intensity, such as... Figure 8a , Figure 8b As shown, its linear range (10-1000 ng / ml) includes the clinical treatment range of clozapine (350-600 ng / ml), thus enabling the monitoring of blood drug concentration; the secondary mass spectrum of the sample with the lowest detectable concentration of 10 ng / ml is shown in the figure. Figure 8b As shown.

[0068] Depend on Figure 3 Figure 8 shows that, based on the measured standard samples, ionization stability, ionization efficiency, sensitivity of the detected samples, and specific applications such as surface extraction and blood drug concentration monitoring, the capillary electrospray ion source device provided in this embodiment of the invention, combined with a small mass spectrometer, can analyze different substances such as drugs and peptides. It is multifunctional and can maintain a stable signal over a long period. Sufficient time and a stable signal ensure sufficient mass spectrometry and multiplex tandem mass spectrometry analysis of multiple analytes in the sample; its sensitivity can reach 1 ng / ml. The ion source device of this invention can also directly analyze trace substances on the surface, enabling rapid screening of drugs. This solves the problem that traditional drug detection and analysis methods are often performed in the laboratory, are time-consuming, and cannot meet the needs of on-site analysis. The ion source device of this invention can also be used with a simple blood sample pretreatment process to achieve blood drug concentration monitoring. In summary, the simple and low-cost ion source device of this invention can achieve the effect of conventional ESI ion sources.

[0069] Therefore, the capillary electrospray ionization source device of the present invention utilizes capillary action for sampling and sample transfer, eliminating the need for complex ionization devices. The device is simple, inexpensive, and the capillary is portable and not easily damaged, making detection convenient and fast, significantly reducing system complexity, and providing high ionization efficiency. It can realize integrated operations such as direct liquid sampling, solid surface extraction, and electrospray ionization analysis, facilitating the miniaturization of micro mass spectrometers while expanding their functions.

[0070] While the invention and its advantages have been described in detail, it should be understood that various changes, substitutions, and modifications can be made without departing from the spirit and scope of the invention as defined by the appended claims. Furthermore, the scope of this application is not limited to the specific embodiments of the processes, apparatus, means, methods, and steps described in the specification. Those skilled in the art will readily understand from the disclosure of this invention that existing and future processes, apparatus, means, methods, or steps that perform substantially the same function or obtain substantially the same results as the corresponding embodiments described herein can be used according to the invention. Therefore, the appended claims are intended to include such processes, apparatus, means, methods, or steps within their scope.

Claims

1. A capillary electrospray ion source device, characterized in that, The device includes a housing with vertically connected sections. Inside the housing, from top to bottom, are a vertically movable pressing sleeve, a conical electrode, and a clamp. The pressing sleeve protrudes from the housing and contains a sampling capillary. The bottom of the pressing sleeve is connected to the conical electrode. The sampling capillary abuts against the upper end of the conical electrode. The conical electrode has a conical hole. A spray capillary is embedded in the lower end of the sampling capillary. The spray capillary passes through the conical hole of the conical electrode, through the clamp, and is held by the clamp. The cone electrode is held by a gripper, with the other end of the gripper having a claw for gripping the spray capillary. Both the pressing sleeve and the gripper are provided with a spring-loaded component. When the pressing sleeve is pressed, the pressing sleeve presses the cone electrode and pushes the gripper to release the spray capillary. When the pressing sleeve is released, the pressing sleeve, the cone electrode, and the gripper reset under the action of the spring-loaded component, thus gripping the spray capillary.

2. The capillary electrospray ion source device according to claim 1, characterized in that, The spring-loaded component of the pressing sleeve includes a spring and a spring-loaded limiter. The spring-loaded limiter is formed by a protrusion on the outer wall of the pressing sleeve matching the shoulder step surface of the inner wall cavity of the housing. The spring is sleeved between the protrusion on the outer wall of the pressing sleeve and the conical electrode.

3. The capillary electrospray ion source device according to claim 1 or 2, characterized in that, The clamp includes a clamping rod for housing the spray capillary and a spring-loaded component. One end of the clamping rod is connected to the conical electrode, and the other end of the clamping rod is provided with a jaw. The spring-loaded component includes a protrusion on the outer wall of the clamping rod, a fixing member, and a spring sleeved between the protrusion on the outer wall of the clamping rod and the fixing member. The fixing member is fixed in the cavity at one end of the housing and sleeved outside the end of the clamping rod with the jaw, forming a cavity between the fixing member and the clamping rod that allows the clamping rod to move up and down. When the clamping rod moves downward, the jaw disengages from the fixing member, releasing the clamped spray capillary. When the clamping rod resets, the jaw retracts into the fixing member, clamping the spray capillary.

4. The capillary electrospray ion source device according to claim 1, characterized in that, The housing includes an upper outer shell and a lower outer shell, which are connected by threads or by snap-fit.

5. The capillary electrospray ion source device according to claim 1, characterized in that, The sampling capillary is a capillary with an outer diameter of 0.69-2 mm and an inner diameter of 590-1900 μm.

6. The capillary electrospray ion source device according to claim 1, characterized in that, The spray capillary uses a capillary with an outer diameter of 150-360 μm and an inner diameter of 75-150 μm.

7. The capillary electrospray ion source device according to claim 1, characterized in that, The upper end of the spray capillary is embedded 1-3 mm inside the sampling capillary.

8. A mass spectrometer, characterized in that, The device includes the capillary electrospray ion source device according to any one of claims 1-7.

Images