A high-throughput ICP torch and its application and mass spectrometry analysis method
By designing a high-throughput ICP torch, using a conical contraction section and non-magnetic materials, combined with an alternating electromagnetic field and cooling water, the problems of limited analysis throughput and speed of traditional ICP torches in Cy-TOF mass spectrometry flow cytometers are solved, rapid ionization and effective cooling are achieved, and the stability and life of the equipment are improved.
Patent Information
- Application Number
- CN202411051419.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-08-01
- Publication Date
- 2025-09-30
- Estimated Expiration
- 2044-08-01
AI Technical Summary
Traditional ICP torches are limited in analytical throughput and speed in Cy-TOF mass spectrometry flow cytometers. High energy consumption leads to overheating and signal interference, while low cooling efficiency affects device stability and lifespan.
A high-throughput ICP torch is designed, which adopts a tapered contraction section and non-magnetic materials, combined with an alternating electromagnetic field and cooling water to improve plasma focusing and energy density, reduce coil power and gas flow, and achieve rapid ionization and effective cooling.
It significantly improves analysis speed and equipment stability, reduces energy consumption, extends instrument life, and solves key technical problems of traditional ICP torches in high-throughput analysis.
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Figure CN119069336B_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of mass spectrometry analysis, and in particular to a high-throughput ICP torch and its application and a mass spectrometry analysis method. Background Art
[0002] Modern flow cytometry is renowned for its high throughput and rapid analytical capabilities, with traditional fluorescence flow cytometers excelling in these areas. However, they face challenges when performing elemental and component analysis. Fluorescent markers have broad emission spectra and are prone to spectral overlap. This not only limits the number of detectable channels to fewer than 20 but also can lead to complex bleed-through issues, requiring tedious signal compensation calculations.
[0003] In recent years, Cy-TOF mass spectrometry has overcome these limitations, providing a highly accurate means of multi-element analysis. Cy-TOF stands for Mass Cytometry, also known as "Cytometry by Time-of-Flight." Compared to standard flow cytometry, Cy-TOF can analyze hundreds of channels without cross-talk, features a rich metal labeling system, and offers extremely low background signal.
[0004] Although Cy-TOF technology has significant application potential in biomedicine and materials science, its low cell throughput limits its application in high-throughput analysis scenarios. To overcome these limitations, further optimization of ICP torch design is needed to increase analysis speed and cell throughput, enabling Cy-TOF technology to better meet the needs of modern scientific research and clinical practice. Summary of the Invention
[0005] In order to overcome the problems existing in the related art, the purpose of the present invention is to provide a high-throughput ICP torch and its application and mass spectrometry analysis method.
[0006] In a first aspect, the present application provides a high-throughput ICP torch with a centrifuge tube cooling structure, comprising a sample pipe and a sheath gas pipe coaxially arranged with the sample pipe;
[0007] The sheath gas pipeline includes an air inlet section, an intermediate section and a contraction section with a conical structure connected in sequence. The sample pipeline outlet is arranged on the inner side of the air inlet section or the intermediate section. The sample pipeline is used to guide the sample gas into the sheath gas pipeline. The inlet of the contraction section is connected to the intermediate section. The outlet of the contraction section is the sheath gas pipeline outlet. The inlet diameter of the contraction section is larger than the outlet diameter of the contraction section. The contraction section is used to concentrate the energy in the torch tube.
[0008] In one embodiment, the acute angle formed by the straight line where the side wall of the contraction section is located and the straight line where the side wall of the middle section is located is 15-45°.
[0009] In one embodiment, an auxiliary pipeline for providing auxiliary gas to the sheath gas pipeline is further included, and the auxiliary pipeline is arranged outside the outlet of the sample pipeline and inside the gas inlet section or the middle section.
[0010] In one embodiment, the device further comprises a coil disposed around the outside of the sheath gas pipe, wherein the coil is used to generate an alternating electromagnetic field.
[0011] In one embodiment, cooling water is passed into the coil, and the cooling water is used to reduce the temperature of the coil.
[0012] In one embodiment, the sample pipe and the sheath gas pipe are both made of non-magnetic materials.
[0013] In one embodiment, a conical opening is provided at the outlet of the sample pipe, the inlet diameter of the conical opening is smaller than the outlet diameter of the conical opening, the inlet of the conical opening is connected to the outlet of the sample pipe, and the outlet of the conical opening is provided on the inner side of the air inlet section or the middle section.
[0014] In one embodiment, an expansion section is provided between the air intake section and the middle section. The expansion section is a conical structure. The inlet of the expansion section is connected to the air intake section, and the outlet of the expansion section is connected to the middle section. The inlet diameter of the expansion section is smaller than the outlet diameter of the contraction section.
[0015] In a second aspect, the present application also provides an application of the above-mentioned high-throughput ICP torch in an inductively coupled plasma mass spectrometer.
[0016] In a third aspect, the present application also provides a mass spectrometry analysis method using the above-mentioned high-throughput ICP torch, the method comprising:
[0017] S1. Sample preparation: Label cell samples with antibodies tagged with metal elements;
[0018] S2. Cell atomization and delivery: suspending a labeled cell sample in a liquid medium, introducing a solution containing the cell sample into a nebulizer via a sample delivery system, converting the cell sample into an aerosol state through atomization and entering a nebulization chamber. A heating device outside the nebulization chamber heats and evaporates water on the cell surface, while simultaneously introducing the dispersed cells into the middle section of the high-throughput ICP torch described in any one of claims 1-8; introducing a carrier gas at a flow rate of 0.8-1.0 L / min into the high-throughput ICP torch through the nebulizer, and introducing a sheath gas at a flow rate of 6-8 L / min into the sheath gas line;
[0019] S3. Plasma ionization: Control the RF power supply to provide 600-800 W, 26.5-27.5 MHz RF current to the coil outside the sheath gas line, generating plasma in the high-throughput ICP torch. The plasma completely vaporizes, dissociates, and ionizes the cell sample, generating ions containing the metal element tags within the cell.
[0020] S4. Ion transmission and analysis: The generated ions enter the ion transmission module through the mass spectrometer interface. The ion lens system focuses the ion beam. The quadrupole transmission rod stably transmits the ions to the mass analysis module. The ions are separated according to the mass-to-charge ratio. The separated ions are detected by the detector, and the generated electrical signals are converted into digital signals. The signals are collected by the acquisition card and transmitted to the host computer.
[0021] The beneficial effects of the present invention are:
[0022] The high-throughput ICP torch features a tapered, conical section that significantly increases the ionization rate of cell samples in the plasma. The tapered section provides a concentrated high-power density area, enabling rapid and sufficient ionization of cell samples, thereby increasing overall analysis speed and meeting the analytical requirements of flow cytometry.
[0023] The high-throughput ICP torch of the present invention can achieve efficient ionization at a relatively low coil power (600-800W), thus reducing energy consumption. The combination of efficient ionization and low energy consumption not only improves analysis efficiency but also avoids overheating and signal interference, thereby improving the stability of the equipment and the reliability of long-term operation.
[0024] The high-throughput ICP torch of the present invention does not require a high gas flow rate under equivalent power conditions, enabling effective cooling even at lower gas flow rates, thus preventing torch overheating and extending the instrument's service life. The high-throughput ICP torch of the present invention also boasts an ionization distance approximately 10 mm longer than that of conventional torches. This rapid ionization process not only accelerates solvent evaporation, particle vaporization, and atomic ionization, but also effectively addresses the issue of insufficient sample processing throughput associated with conventional torches.
[0025] In summary, through these technical means, the high-throughput ICP torch of the present invention improves the convective heat transfer efficiency and shows significant advantages in terms of ionization rate, energy consumption, cooling efficiency and analytical throughput. Even at lower gas flow rates, it can achieve the same cooling effect as the traditional Fasse 1 torch, ensuring the stable operation of the equipment in high-throughput analysis, extending the equipment service life, reducing maintenance frequency and cost, and solving the key technical problems of the traditional Fasse 1 torch in high-throughput analysis applications.
[0026] Other features and advantages of the present invention will be described in the following description, and in part will become apparent from the description, or will be understood by practicing the present invention. The purposes and other advantages of the present invention can be realized and obtained by the structures particularly pointed out in the written description, claims, and drawings. BRIEF DESCRIPTION OF THE DRAWINGS
[0027] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments recorded in the present application. For ordinary technicians in this field, other drawings can also be obtained based on these drawings.
[0028] Figure 1 Schematic diagram of the structure of the high-throughput ICP torch in Example 1 of the present invention;
[0029] Figure 2 Schematic diagram of the structure of another high-throughput ICP torch in Example 1 of the present invention;
[0030] Figure 3 Schematic diagram of the structure of another high-throughput ICP torch in Example 1 of the present invention;
[0031] Figure 4 Schematic diagram of the system flow of the mass spectrometry analysis method in Example 1 of the present invention;
[0032] Figure 5 Schematic diagram of the high-throughput ICP torch and the traditional Fasse l torch in Example 1 of the present invention;
[0033] Figure 6 Schematic diagram of the high-throughput ICP torch and the traditional Fasse l torch in Example 1 of the present invention.
[0034] Reference numerals:
[0035] 1. Sheath gas pipeline; 11. Air inlet section; 12. Middle section; 13. Contraction section; 14. Expansion section; 2. Sample pipeline; 21. Conical opening; 3. Auxiliary pipeline. DETAILED DESCRIPTION
[0036] Alternative embodiments of the present invention will be described in more detail below with reference to the accompanying drawings. Although the accompanying drawings illustrate alternative embodiments of the present invention, it should be understood that the present invention can be implemented in various forms and should not be limited by the embodiments described herein. Rather, these embodiments are provided to make the present invention more thorough and complete and to fully convey the scope of the present invention to those skilled in the art.
[0037] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which the present invention pertains. The terms used herein in the specification of the present invention are for the purpose of describing specific embodiments only and are not intended to limit the present invention. The singular forms "a", "the" and "the" used in the present invention and the appended claims are also intended to include plural forms unless the context clearly indicates otherwise. It should also be understood that the term "and / or" used herein refers to and encompasses any or all possible combinations of one or more associated listed items.
[0038] It should be understood that although the present invention may use terms such as "first", "second", and "third" to describe various information, these information should not be limited to these terms. These terms are only used to distinguish the same type of information from each other.
[0039] Unless otherwise specified, the methods and equipment used in the present invention are all conventional reagents, methods and equipment in this technical field.
[0040] To facilitate understanding of the embodiments of the present invention, we first explain the related art ICP torch. In the prior art, the application of traditional Fassel ICP torches in mass cytometry (CyTOF) faces many challenges. Mass cytometry combines flow cytometry and mass spectrometry technologies, capable of simultaneously detecting multiple elements and elements, but its analytical throughput and speed are significantly limited. Traditional ICP torches exhibit several key issues in CyTOF applications:
[0041] 1. Slow sample ionization. This is because the traditional Fassel torch design fails to effectively concentrate the high power density area, resulting in inefficient and inadequate ionization of the sample in the plasma. This limits the overall analysis speed of the CyTOF instrument and makes it unable to meet the analytical requirements of flow cytometry.
[0042] 2. To ensure that the ICP ion source closely matches the throughput requirements of flow cytometry, high power (typically 1500W) is typically applied to the torch coil during cell analysis to rapidly ionize the cells. This not only results in high energy consumption but also creates potential overheating and signal interference issues. Furthermore, it also fails to achieve the analytical throughput required by Cy-TOF. High-power operation limits the stability and long-term reliability of the device.
[0043] 3. At the same gas flow rate, increasing the coil power of the Fassel torch may result in lower convective heat transfer efficiency. The lower gas velocity cannot effectively remove heat, resulting in poor cooling of the torch outer tube. Over extended operation, the torch can easily overheat, affecting instrument stability and service life, and even causing the torch to melt.
[0044] These technical issues not only limit the performance of traditional ICP torches in CyTOF but also restrict the application of mass spectrometry flow cytometry in high-throughput, high-efficiency analysis. To address these issues, innovative ICP torch designs are needed to increase the ionization rate of cell samples, reduce energy consumption, and optimize cooling efficiency, thereby enhancing the overall performance and application range of CyTOF technology. Based on this, the present application provides a high-throughput ICP torch.
[0045] As attached Figure 2 As shown, a high-throughput ICP torch provided in Example 1 of the present application includes a sample pipe 2 and a sheath gas pipe 1 coaxially arranged with the sample pipe 2;
[0046] The sheath gas pipeline 1 includes an air inlet section 11, an intermediate section 12 and a conical contraction section 13 connected in sequence. The outlet of the sample pipeline 2 is arranged on the inner side of the air inlet section 11 or the intermediate section 12. The sample pipeline 2 is used to guide the sample gas into the sheath gas pipeline 1. The inlet of the contraction section 13 is connected to the intermediate section 12. The outlet of the contraction section 13 is the outlet of the sheath gas pipeline 1. The inlet diameter of the contraction section 13 is larger than the outlet diameter of the contraction section 13; the contraction section 13 is used to concentrate the energy in the torch tube.
[0047] It should be noted that the principle by which the contraction section 13 can focus the plasma is mainly based on the pinch effect and related principles of fluid mechanics. When the plasma passes through the contraction section 13 at the outlet of the torch tube, the cross-sectional area of the channel decreases. According to the continuity equation of fluid mechanics, the flow velocity will increase when the mass flow rate remains unchanged. At the same time, since the plasma is composed of charged particles (including ions, electrons, etc.), its movement is affected by the electromagnetic field. In the contraction section 13 area, the Lorentz force generated by the interaction between the current and the magnetic field will cause the charged particles in the plasma to be subjected to a centripetal force, prompting them to gather toward the central axis.
[0048] This pinching effect is similar to "compressing" or "focusing" the plasma together, making the particle distribution of the plasma more concentrated and the energy more dense; specifically, in the contraction section 13, the magnetic field generated by the current will exert an inward Lorentz force on the charged particles. Under the action of this force, the charged particles will move radially toward the central axis, thereby forming a self-pinching phenomenon. When the current is strong enough, this pinching effect can form a high-temperature, high-density plasma region near the axis.
[0049] In addition, the design of the contraction section 13 also helps to reduce the diffusion of plasma. In the absence of the contraction section 13, the plasma may diffuse more easily to the surroundings, resulting in energy dispersion. The presence of the contraction section 13 limits the diffusion range of the plasma, allowing it to maintain a relatively concentrated state. The focusing effect provided by the contraction section 13 can increase the energy density of the plasma and enhance its interaction efficiency with matter, thereby more efficiently carrying out various physical and chemical reactions such as the ionization process.
[0050] like Figure 6 As shown, the high-throughput ICP torch of the present invention adopts a design with a tapered contraction section 13, which significantly improves the ionization rate of cell samples in the plasma. The tapered contraction section 13 can provide a concentrated high-power density area, so that the cell samples can be ionized quickly and fully, thereby improving the overall analysis speed and meeting the analysis requirements of flow cytometry technology.
[0051] The high-throughput ICP torch of the present invention can achieve efficient ionization at a relatively low coil power (600-800W), thus reducing energy consumption. The combination of efficient ionization and low energy consumption not only improves analysis efficiency but also avoids overheating and signal interference, thereby improving the stability of the equipment and the reliability of long-term operation.
[0052] like Figure 5 As shown, the high-throughput ICP torch of the present invention does not need to provide a high gas flow rate under the same power conditions, so that effective cooling can be achieved even at a lower gas flow rate, avoiding torch overheating and extending the service life of the instrument. The high-throughput ICP torch of the present invention also has an ionization distance that is approximately 10 mm longer than that of traditional torches. This rapid ionization process not only accelerates solvent evaporation, particle vaporization and atomic ionization, but also effectively solves the problem of insufficient sample processing throughput of traditional torches.
[0053] In summary, through these technical means, the high-throughput ICP torch of the present invention improves the convective heat transfer efficiency and shows significant advantages in terms of ionization rate, energy consumption, cooling efficiency and analytical throughput. Even at lower gas flow rates, it can achieve the same cooling effect as the traditional Fasse 1 torch, ensuring the stable operation of the equipment in high-throughput analysis, extending the equipment service life, reducing maintenance frequency and cost, and solving the key technical problems of the traditional Fasse 1 torch in high-throughput analysis applications.
[0054] In an optional embodiment of the present invention, the acute angle formed by the straight line where the side wall of the contraction section 13 is located and the straight line where the side wall of the middle section 12 is located is 15-45°; Figure 2α shown; in actual application, by setting the angle range formed by the straight line where the side wall of the contraction section 13 is located and the straight line where the side wall of the middle section 12 is located, the contraction section 13 reduces the cross-sectional area of the outlet, so that the fluid flow rate will increase; in the case of generating plasma, the increase in flow rate means that the plasma can flow more concentratedly, thereby achieving a focusing effect. After focusing, the particle distribution of the plasma is denser and the energy is more concentrated.
[0055] In an optional manner in an embodiment of the present invention, the length of the contraction section 13 is 5-15 mm. By setting the length of the contraction section 13 and the contraction section 13 with a conical structure, the aggregation range and aggregation density of the plasma are limited, and while ensuring the conventional functions of the ICP torch, the energy density of the plasma is increased and the efficiency of its interaction with matter is enhanced.
[0056] In an optional manner in an embodiment of the present invention, the ratio of the outlet diameter of the contraction section 13 to the inlet diameter of the contraction section 13 is (3-5):6; by setting the ratio of the outlet diameter of the contraction section 13 to the inlet diameter of the contraction section 13 and the conical structure of the contraction section 13, the diffusion range of the plasma is limited under the action of the two, and under the premise of ensuring the conventional functions of the ICP torch tube, the plasma can be kept in a relatively concentrated state, thereby improving the energy density of the plasma and enhancing the efficiency of its interaction with matter.
[0057] By setting the length of the contraction section 13 and the ratio range of the outlet diameter to the inlet diameter, the high-throughput ICP torch of the present invention can better concentrate the plasma flow, thereby achieving a focusing effect, with denser particle distribution and more concentrated energy.
[0058] Optionally, the contraction section 13 is made of a non-magnetic material with good thermal conductivity, and the non-magnetic material may be an aluminum alloy, demagnetized austenitic stainless steel (304 and 316 stainless steel), or the like.
[0059] In an optional manner in the embodiment of the present invention, the sample pipe 2 and the sheath gas pipe 1 can be connected by high-temperature welding, precision sleeve connection, mechanical fixation, etc.;
[0060] It should be noted that high-temperature welding: during the manufacturing process, high temperature is used to melt the contact parts of the sample pipe 2 and the sheath gas pipe 1, so that they are fused together to form a firm connection. This method can provide better sealing and stability; precision sleeve connection: the sample pipe 2 is accurately sleeved inside the sheath gas pipe 1, and the connection is achieved through tight fit and appropriate fixing measures. Some high-temperature resistant adhesives or sealing materials can be used to enhance the stability and sealing of the connection; mechanical fixation: special clips, clasps or fixing devices can be used to fix the sample pipe 2 and the sheath gas pipe 1 together. This method requires ensuring that the fixing parts can withstand high temperatures and will not affect the generation and operation of plasma.
[0061] It should be noted that the specific connection method will vary depending on the design, manufacturing process and usage requirements of the ICP tube, and will not be listed here one by one.
[0062] An optional embodiment of the present invention further includes an auxiliary pipeline 3 for providing auxiliary gas to the sheath gas pipeline 1, wherein the auxiliary pipeline 3 is arranged outside the outlet of the sample pipeline 2 and inside the gas inlet section 11 or the middle section 12;
[0063] It should be noted that if Figure 1 As shown, an auxiliary pipe 3 is provided to provide auxiliary gas, and the auxiliary gas and sheath gas can be the same, for example, both are argon. The three-layer tube realizes the functions of cooling and generating a high-temperature plasma torch through "sheath gas" and "auxiliary gas" respectively, while in the double-layer tube, the "sheath gas" plays a cooling role and also plays a role in generating a high-temperature plasma torch. At the same time, the sheath gas can play a certain role in gathering plasma under this conical structure.
[0064] Optionally, the auxiliary pipe 3 is made of non-magnetic material; optionally, the non-magnetic material may be one of PEEK material, quartz, and ceramic;
[0065] It should be noted that the ICP torch operates in a high-frequency electromagnetic field generated by a coil. Non-magnetic materials do not generate magnetic interference, which is crucial to maintaining the stability and consistency of the plasma. Magnetic materials may be affected by induced currents, resulting in uneven heating and plasma instability. In addition, non-magnetic materials avoid eddy current losses and thermal effects in high-frequency electromagnetic fields.
[0066] Optionally, the auxiliary pipeline 3 can be connected to the sample pipeline 2 and / or the sheath gas pipeline 1 by high-temperature welding, precision sleeve connection, mechanical fixation, etc. In practical applications, for example, high-temperature welding: during the manufacturing process, high temperature is used to melt the contact parts of the auxiliary pipeline 3 and the sheath gas pipeline 1, so that they are fused together to form a firm connection. This method can provide better sealing and stability; precision sleeve connection: the auxiliary pipeline 3 is accurately sleeved inside the sheath gas pipeline 1, and the connection is achieved through tight fit and appropriate fixing measures. Some high-temperature resistant adhesives or sealing materials can be used to enhance the stability and sealing of the connection; mechanical fixation: special clips, clasps or fixing devices can be used to fix the auxiliary pipeline 3 and the sheath gas pipeline 1 together. This method needs to ensure that the fixing parts can withstand high temperatures and will not affect the generation and operation of plasma.
[0067] like Figure 1-3 As shown, an optional embodiment of the present invention further includes a coil arranged around the outside of the sheath gas pipe 1, and the coil is used to generate an alternating electromagnetic field;
[0068] It should be noted that the coil is used to excite and maintain the plasma. When a high-frequency current passes through the coil, an alternating magnetic field is generated around the torch. The high-frequency electromagnetic field generated by the coil effectively couples the radio frequency energy into the plasma, providing energy for the formation and maintenance of the plasma. It ionizes working gases such as argon to produce charged particles, thereby forming a plasma. This helps maintain the stability and uniformity of the plasma, ensuring the repeatability and accuracy of the analysis process. It provides the necessary environment for the excitation of the sample, so that the elements in the sample can be excited and emit characteristic spectra for subsequent detection and analysis.
[0069] In an optional manner in the embodiment of the present invention, cooling water is introduced into the coil, and the cooling water is used to reduce the temperature of the coil;
[0070] It should be noted that when high-frequency current passes through the coil, a large amount of Joule heat is generated, causing the coil temperature to rise rapidly. The introduction of cooling water can promptly remove this heat, preventing the coil from being damaged by overheating and extending the coil's service life. At the same time, high temperature will cause the coil's resistance to increase, affecting the efficiency and stability of current flow. Cooling can keep the coil's resistance relatively stable, thereby ensuring the stability and consistency of the generated electromagnetic field, which is conducive to the stable excitation and maintenance of the plasma.
[0071] In actual applications, if the coil overheats, it may affect the performance and accuracy of the entire instrument, and even cause instrument failure. Introducing cooling water into the coil helps maintain the instrument within the normal operating temperature range, ensuring that the instrument can operate stably for a long time and improve the reliability of the analysis results. In the case of continuous analysis of a large number of samples for a long time, without effective cooling by cooling water, the coil may quickly reach the high temperature limit, resulting in interruption of the analysis work. In some experiments with extremely high requirements for analytical accuracy, even slight changes in the coil temperature may affect the results. At this time, stable cooling is particularly important.
[0072] In an optional manner in the embodiment of the present invention, the sample pipe 2 and the sheath gas pipe 1 are both made of non-magnetic materials;
[0073] It should be noted that the ICP torch operates in a high-frequency electromagnetic field generated by a coil. Non-magnetic materials do not generate magnetic interference, which is crucial to maintaining the stability and consistency of the plasma. Magnetic materials may be affected by induced currents, resulting in uneven heating and plasma instability. In addition, non-magnetic materials avoid eddy current losses and thermal effects in high-frequency electromagnetic fields.
[0074] Optionally, the non-magnetic material may be one of PEEK material, quartz, and ceramics; optionally, the non-magnetic material is corrosion-resistant and can be used to process acidic samples.
[0075] like Figure 2 As shown, in an optional manner in an embodiment of the present invention, a conical opening 21 is provided at the outlet of the sample pipe 2, the inlet diameter of the conical opening 21 is smaller than the outlet diameter of the conical opening 21, the inlet of the conical opening 21 is connected to the outlet of the sample pipe 2, and the outlet of the conical opening 21 is arranged on the inner side of the air inlet section 11 or the middle section 12.
[0076] It should be noted that due to the shape and structure of the conical opening 21, the sample gas will produce certain flow field changes when passing through the conical opening 21, so that the gas can utilize the space more effectively, thereby forming a higher flow velocity distribution similar to that required by the traditional torch tube; at the same time, it will also cause the turbulence of the gas to increase. Turbulence can promote gas mixing and energy transfer, making the gas more uniform and stable during the flow process, thereby achieving better flow effects even at lower flow rates.
[0077] like Figure 2-3As shown, in an optional manner in the embodiment of the present invention, an expansion section 14 is further provided between the air inlet section 11 and the middle section 12. The expansion section 14 is a conical structure. The inlet of the expansion section 14 is connected to the air inlet section 11, and the outlet of the expansion section 14 is connected to the middle section 12. The inlet diameter of the expansion section 14 is smaller than the outlet diameter of the contraction section 13.
[0078] It should be noted that the provision of the expansion section 14 at the torch inlet enables the gas flow rate required by a conventional torch to be achieved with a lower gas flow rate. This is primarily due to the following: First, the expansion section 14 increases the cross-sectional area of the gas flow channel. With a constant mass flow rate, the gas flow rate decreases accordingly as the channel cross-sectional area increases. However, due to the special shape and structure of the expansion section 14, the gas flow field undergoes certain changes as it passes through the expansion section 14, allowing the gas to utilize space more efficiently, thereby forming a higher flow rate distribution at the outlet similar to that required by a conventional torch.
[0079] Secondly, the expansion section 14 may cause the turbulence of the gas to be enhanced. The turbulence can promote the mixing and energy transfer of the gas, making the gas more uniform and stable during the flow process, thereby achieving a better flow effect at a lower flow rate.
[0080] Example 2 of the present application provides an application of the high-throughput ICP torch tube in Example 1 in an inductively coupled plasma mass spectrometer.
[0081] like Figure 4 As shown, the third embodiment of the present application provides a mass spectrometry analysis method using the high-throughput ICP torch in the first embodiment, the method comprising:
[0082] S1. Sample preparation: Label cell samples with antibodies tagged with metal elements;
[0083] S2. Cell atomization and delivery: suspending a labeled cell sample in a liquid medium, introducing a solution containing the cell sample into a nebulizer via a sample delivery system, converting the cell sample into an aerosol state through atomization and entering a nebulization chamber. A heating device outside the nebulization chamber heats and evaporates water on the cell surface, while simultaneously introducing the dispersed cells into the middle section 12 of the high-throughput ICP torch described in any one of claims 1-8; introducing a carrier gas at a flow rate of 0.8-1.0 L / min into the high-throughput ICP torch through the nebulizer, and introducing a sheath gas at a flow rate of 6-8 L / min into the sheath gas line 1;
[0084] S3. Plasma ionization: Control the RF power supply to provide 600-800 W, 26.5-27.5 MHz RF current to the coil outside the sheath gas line 1, so that the high-throughput ICP torch forms a plasma. The cell sample is completely vaporized, dissociated, and ionized by the plasma, generating ions containing the metal element label in the cell;
[0085] S4. Ion transmission and analysis: The generated ions enter the ion transmission module through the mass spectrometer interface. The ion lens system focuses the ion beam. The quadrupole transmission rod stably transmits the ions to the mass analysis module. The ions are separated according to the mass-to-charge ratio. The separated ions are detected by the detector, and the generated electrical signals are converted into digital signals. The signals are collected by the acquisition card and transmitted to the host computer.
[0086] In an optional manner in an embodiment of the present invention, sample preparation further includes cell collection and preparation, wherein cells are collected from a sample (such as blood, tissue, or cultured cells), washed with PBS (phosphate-buffered saline) to remove proteins in the serum and culture medium; cells are counted using a cell counter or hemocytometer, and the cell concentration is adjusted to an appropriate level, such as 1 x 10^6 cells / mL;
[0087] In an optional manner in an embodiment of the present invention, the cell sample is labeled with an antibody having a metal element label, specifically comprising:
[0088] Select antibodies targeting the target protein. The antibodies are pre-labeled with metal elements. Commonly used metal elements include europium, thulium, gadolinium, indium, lanthanum, etc.
[0089] According to experimental needs, various metal-labeled antibodies were mixed together and labeled according to standard ratios;
[0090] Fix cells with a fixative (e.g., formaldehyde) to preserve cell morphology and antigenicity;
[0091] The fixed cells are suspended in a mixture of metal-labeled antibodies and incubated at 4°C for 30 minutes to 1 hour.
[0092] Wash the cells with PBS or other suitable buffer to remove unbound antibody.
[0093] The signal intensity of the metal element can be used to determine the number of cells that can bind to the antibody. For example, if an antibody that only cancer cells can bind to is used, and this antibody has a metal marker, the signal intensity of the corresponding element can be seen in the spectrum to be very high, which can be used to determine whether there is cancerous tissue in the collected sample.
[0094] Optionally, the data generated by the host computer includes elemental labeling information for each cell. The collected data can be analyzed by data processing software to generate a multi-dimensional information map of the cell population. The generated map can display multiple parameters of each cell, such as protein expression levels, cell cycle status, etc.
[0095] Optionally, the resulting data can be used for biological research, helping researchers understand the complex functions and interactions of cells. For example, it can be used for tumor microenvironment research, immune cell phenotyping, etc.
[0096] By adopting the high-throughput ICP torch tube in Example 1 for mass spectrometry analysis, the convective heat transfer efficiency is improved, and significant advantages are shown in terms of ionization speed, energy consumption, cooling efficiency and analysis throughput, ensuring the stable operation of the equipment in high-throughput analysis, extending the service life of the equipment, reducing maintenance frequency and cost, and improving the efficiency of mass spectrometry analysis.
[0097] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the various embodiments of the present invention.
Claims
1. A high-throughput ICP torch, characterized in that It includes a sample pipeline and a sheath gas pipeline coaxially arranged with the sample pipeline; The sheath gas pipeline includes an air inlet section, an intermediate section, and a conical contraction section connected in sequence. The outlet of the sample pipeline is arranged inside the air inlet section or the intermediate section. The sample pipeline is used to guide the sample gas into the sheath gas pipeline. The inlet of the contraction section is connected to the intermediate section. The outlet of the contraction section is the outlet of the sheath gas pipeline. The inlet diameter of the contraction section is larger than the outlet diameter of the contraction section. The contraction section is used to concentrate the energy in the torch tube. A tapered opening is provided at the outlet of the sample pipe, wherein the inlet diameter of the tapered opening is smaller than the outlet diameter of the tapered opening, the inlet of the tapered opening is connected to the outlet of the sample pipe, and the outlet of the tapered opening is provided inside the air inlet section or the middle section; An expansion section is further provided between the air intake section and the middle section. The expansion section is a conical structure. The inlet of the expansion section is connected to the air intake section, and the outlet of the expansion section is connected to the middle section. The inlet diameter of the expansion section is smaller than the outlet diameter of the contraction section.
2. The high-throughput ICP torch according to claim 1, wherein: The acute angle formed by the straight line where the side wall of the contraction section is located and the straight line where the side wall of the middle section is located is 15-45°.
3. The high-throughput ICP torch according to claim 1, wherein: Also includes: An auxiliary pipeline for providing auxiliary gas to the sheath gas pipeline is arranged outside the outlet of the sample pipeline and inside the gas inlet section or the middle section.
4. The high-throughput ICP torch according to claim 1, wherein: The device also includes a coil which is arranged around the outside of the sheath gas pipeline and is used to generate an alternating electromagnetic field.
5. The high-throughput ICP torch according to claim 4, wherein: Cooling water is passed into the coil, and the cooling water is used to reduce the temperature of the coil.
6. The high-throughput ICP torch according to claim 1, wherein: The sample pipe and the sheath gas pipe are both made of non-magnetic materials.
7. Use of the high-throughput ICP torch according to any one of claims 1 to 6 in an inductively coupled plasma mass spectrometer.
8. A mass spectrometry analysis method using the high-throughput ICP torch according to any one of claims 1 to 6, characterized in that: The method comprises, S1. Sample preparation: Label cell samples with antibodies tagged with metal elements; S2. Cell atomization and delivery: suspending a labeled cell sample in a liquid medium, introducing a solution containing the cell sample into a nebulizer via a sample delivery system, converting the cell sample into an aerosol through atomization and entering a nebulizer chamber. A heating device outside the nebulizer chamber evaporates water on the cell surface, and simultaneously, the dispersed cells are concentratedly introduced into the middle section of a high-throughput ICP torch according to any one of claims 1 to 6. Carrier gas at a flow rate of 0.8-1.0 L / min is introduced into the high-throughput ICP torch through the nebulizer, and sheath gas at a flow rate of 6-8 L / min is introduced into the sheath gas line. S3. Plasma ionization: Control the RF power supply to provide 600-800W, 26.5-27.5MHz RF current to the coil outside the sheath gas line, generating plasma in the high-throughput ICP torch. The plasma completely vaporizes, dissociates, and ionizes the cell sample, generating ions containing the metal element tags within the cell. S4. Ion transmission and analysis: The generated ions enter the ion transmission module through the mass spectrometer interface. The ion lens system focuses the ion beam. The quadrupole transmission rod stably transmits the ions to the mass analysis module. The ions are separated according to the mass-to-charge ratio. The separated ions are detected by the detector, and the generated electrical signals are converted into digital signals. The signals are collected by the acquisition card and transmitted to the host computer.
Citation Information
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