A heating device and mass spectrometry apparatus with nanoelectrospray source

Abstract

A heating device and a mass spectrometry device of a nanoelectrospray source, the heating device comprising: a support body and a heating body arranged on the support body, the heating body being configured to apply a heating effect to an ion transmission path and being provided with an ion transmission channel for the passage of ions or charged droplets; an ion inlet of the ion transmission channel corresponding to an ion outlet of the nanoelectrospray source, and an ion outlet of the ion transmission channel corresponding to an ion inlet of the mass spectrometer. The heating device can significantly improve the atomization and desolvation capability of the nanoelectrospray source, improve the signal response and repeatability, reduce the ion cluster background noise formed by solvent molecules, improve the sensitivity, and avoid the spray stop and signal loss caused by the heat-sensitive drying of the nanoelectrospray ion source at the end of the spray needle.

Description

Technical Field

[0001] This article relates to mass spectrometry and electrospray ionization technology, and more particularly to a mass spectrometry device with a heating device and a nanoliter electrospray source. Background Technology

[0002] Nanoelectrospray ionization (nanoESI) sources are widely used in the analysis of complex biological samples, such as proteomics and metabolomics, due to their low flow rate and high sensitivity. However, their spray stability and ionization efficiency are highly sensitive to the temperature conditions at the nozzle ion outlet. Traditional liquid chromatography-mass spectrometry (LCMS) systems generally lack dedicated temperature control designs for nanoESI, which can easily lead to problems such as premature spray drying, nozzle clogging, or spray instability when using direct heating of the nozzle or hot gas flow assistance.

[0003] On the other hand, most nano- or micro-spray ion sources, lacking dedicated temperature control designs, cannot effectively desolvent the spray droplets, resulting in a large number of solvent molecules encapsulating the ion clusters, thereby reducing the signal-to-noise ratio and exacerbating background noise. Summary of the Invention

[0004] This application provides a mass spectrometry device with a heating device and a nano-electrospray source, which can significantly improve the atomization and desolvation capabilities of the nano-electrospray source, enhance signal response and repeatability, reduce background noise from ion clusters formed by solvent molecule encapsulation, and improve sensitivity.

[0005] This application provides a heating device, which is disposed between a nano-electrospray source and a mass spectrometer along the direction of the atomized ion ejection from the nano-electrospray source. The heating device includes: Supporting entity; A heating element, mounted on the supporting body, is provided with an ion transport channel for ions or charged droplets to pass through, guiding ions or charged droplets formed by nanoliter electrospray to the mass spectrometer. The ion transport channel described herein is not limited to the specific structural form shown in the figures; it can be tubular, cavity-shaped, or other closed or semi-closed transport space forms. Any channel capable of guiding ions or charged droplets along a predetermined path toward the mass spectrometer should be understood as falling within the scope of the ion transport channel described in this application. The ion inlet of the ion transport channel corresponds to the ion outlet of the nanoliter electrospray source, and the ion outlet of the ion transport channel corresponds to the ion inlet of the mass spectrometer.

[0006] In one exemplary embodiment, the distance between the ion inlet of the ion transport channel of the heating element and the ion outlet of the nanoliter electrospray source is set to a distance range of 0.5 to 5 mm that can both avoid heat-sensitive drying of the spray needle and promote desolvation of the droplets.

[0007] In one exemplary embodiment, the heating element includes one or more elements connected in series; The heating temperature of the multiple series-connected heating elements is set to form a gradient change in the direction from the ion outlet toward the ion inlet of the mass spectrometer.

[0008] In an exemplary embodiment, the length range of the ion transport channel of the heating element is set to a length range that enables droplet desolvation and maintains stable ion transport, preferably 5 mm to 30 mm; when multiple heating elements are connected in series, the total length range of their ion transport channels is 10 mm to 100 mm, and the heating temperature of the heating element is set to a temperature range that enables the above-mentioned technical effects, preferably 50°C to 300°C.

[0009] In one exemplary embodiment, the support body is a sealing cover, which is configured to cooperate with the mass spectrometer to fix and shield the ion inlet of the mass spectrometer; The ion outlet of the ion transport channel is connected to the covering space of the sealing cover.

[0010] In one exemplary embodiment, the opening of the sealing cover is flared outwards toward the ion inlet of the mass spectrometer.

[0011] In one exemplary embodiment, the heating element includes a body having a first end face corresponding to the ion outlet of the nanoliter electrospray source and a second end face corresponding to the ion inlet of the mass spectrometer; The ion inlet of the ion transport channel protrudes from the first end face, and the ion outlet of the ion transport channel protrudes from the second end face.

[0012] In one exemplary embodiment, the heating device further includes a heating element and a temperature control element disposed on the heating body, and a controller connected to the heating element and the temperature control element.

[0013] In one exemplary embodiment, the heating device further includes a connector for connecting and positioning the nanoliter electrospray source and the mass spectrometer; The connector includes a first connector connected to the nanoliter electrospray source and a second connector connected to the mass spectrometer. The first connector and the second connector are plugged into each other and locked by a connector.

[0014] This application embodiment also provides a mass spectrometry device for a nanoliter electrospray source, including: a nanoliter electrospray source and a mass spectrometer; the nanoliter electrospray source is configured to spray mist ions, and the mass spectrometer is configured to receive the mist ion signal; The mass spectrometry device of the nano-electrospray source also includes a heating device, as described in any of the above embodiments, disposed between the nano-electrospray source and the mass spectrometer along the direction of the mist ion ejection.

[0015] The heating device in this embodiment is positioned between the nano-electrospray source and the mass spectrometer. It can apply heat to the mist ions and / or charged droplets transported along the ion transport path after the mist ions detach from the nozzle of the nano-electrospray source. This can significantly improve the atomization and desolvation capabilities of the nano-electrospray source, enhance signal response and repeatability, reduce the background noise of ion clusters formed by solvent molecules, improve sensitivity, and avoid spray stoppage and signal loss caused by thermal drying at the nozzle tip of the nano-electrospray ion source.

[0016] Other features and advantages of this application will be set forth in the following description, and will be apparent in part from the description, or may be learned by practicing the application. Other advantages of this application can be realized and obtained by means of the embodiments described in the description and the accompanying drawings. Attached Figure Description

[0017] The accompanying drawings are used to provide an understanding of the technical solutions of this application and constitute a part of the specification. They are used together with the embodiments of this application to explain the technical solutions of this application and do not constitute a limitation on the technical solutions of this application.

[0018] Figure 1 This is a schematic diagram of the connection of the mass spectrometry equipment for the nano-electrospray source in an embodiment of this application; Figure 2 This is a cross-sectional view of the heating element of the heating device according to an embodiment of this application; Figure 3 This is a schematic diagram of multiple heating elements connected in series in the heating device of this application embodiment; Figure 4 Input display images for two organic small molecule samples (oils); Figure 5 The spectral results are for the detection of a small organic molecule sample (oil). Figure 6 This is the spectral result for another small organic molecule sample (oil).

[0019] Reference numerals: 100 for mass spectrometry with nano-electrospray source; 4 for nano-electrospray source; 5 for spray needle; 6 for mass spectrometer; 1, 1a, 1b, 1c for heating elements; 2 for support body; 10 for main body; 101 for ion transmission channel; 110 for ion inlet; 120 for ion outlet; A for first end face; B for second end face; 13 for heating element; 14 for temperature control element; 3 for connecting seat; 31 for first connecting seat; 32 for second connecting seat. Detailed Implementation

[0020] This application describes several embodiments, but these descriptions are exemplary and not limiting, and it will be apparent to those skilled in the art that many more embodiments and implementations are possible within the scope of the embodiments described herein. Although many possible combinations of features are shown in the drawings and discussed in the detailed description, many other combinations of the disclosed features are also possible. Unless specifically limited, any feature or element of any embodiment may be used in combination with, or may replace, any feature or element of any other embodiment.

[0021] This application includes and contemplates combinations of features and elements known to those skilled in the art. The embodiments, features, and elements disclosed in this application can also be combined with any conventional features or elements to form unique inventive solutions. Any feature or element of any embodiment can also be combined with features or elements from other inventive solutions to form another unique inventive solution. Therefore, it should be understood that any feature shown and / or discussed in this application can be implemented individually or in any suitable combination. Therefore, the embodiments are not limited except by the limitations imposed by the appended claims and their equivalents. Furthermore, various modifications and changes can be made within the scope of the appended claims.

[0022] Furthermore, in describing representative embodiments, the specification may have presented methods and / or processes as a specific sequence of steps. However, the method or process should not be limited to the specific order of steps described herein, to the extent that it does not depend on such a specific order. As will be understood by those skilled in the art, other sequences of steps are also possible. Therefore, the specific order of steps set forth in the specification should not be construed as a limitation of the claims. Moreover, the claims concerning the method and / or process should not be limited to the steps performed in the written order, and those skilled in the art will readily understand that these orders can be varied and still remain within the spirit and scope of the embodiments of this application.

[0023] like Figure 1 As shown in the embodiment of this application, the mass spectrometry device 100 with a nano-electrospray source includes a nano-electrospray source 4 and a mass spectrometer 6. The nano-electrospray source 4 is configured to spray mist ions, and the mass spectrometer 6 is configured to receive and analyze the mist ion signals. The mass spectrometry device 100 with a nano-electrospray source also includes a heating device disposed between the nano-electrospray source 4 and the mass spectrometer 6 along the mist ion spray direction.

[0024] like Figure 1 , Figure 2As shown, the heating device includes a heating element 1 and a supporting body 2, with the heating element 1 disposed on the supporting body 2. The heating element 1 is provided with an ion transmission channel 101 through which the mist ions ejected by the nano-electrospray source 4 pass. The ion inlet 110 of the ion transmission channel 101 corresponds to the ion outlet 120 of the nozzle 5 of the nano-electrospray source 4, and the ion outlet 120 of the ion transmission channel 101 corresponds to the ion inlet of the mass spectrometer 6.

[0025] The heating device in this embodiment is disposed between the nano-electrospray source 4 and the mass spectrometer 6. It can apply heat to the mist ions and / or charged droplets transported along the ion transport path after the mist ions detach from the spray needle 5. This can significantly improve the atomization and desolvation capabilities of the nano-electrospray source 4, enhance signal response and repeatability, reduce the background noise of ion clusters formed by solvent molecules, and improve sensitivity.

[0026] like Figure 1 , Figure 3 As shown, heating element 1 includes one or more elements connected in series. The multiple series-connected heating elements 1a, 1b, and 1c create a temperature gradient from the ion outlet of the nozzle 5 towards the ion inlet of the mass spectrometer 6. This temperature gradient is designed to address potential temperature mismatches between solvent atomization and the ion inlet of the mass spectrometer 6. For example, most organic solvents cannot withstand very high temperatures, typically below 100 degrees Celsius, otherwise the spray would dry out and become unusable; however, the ion inlet of the mass spectrometer may exceed 100 degrees Celsius, such as around 200 degrees Celsius or even higher. If such a large temperature difference exists between the two ends, multiple series-connected heating elements 1a, 1b, and 1c can be used to create a gradient heating effect to address this.

[0027] like Figure 3 As shown, in this exemplary embodiment, the length of the ion transport channel 101 of the heating element 1 is set to a length range that enables droplet desolvation and maintains stable ion transport, which is 5 mm to 30 mm; when multiple heating elements 1 are connected in series, the total length of their ion transport channels 101 is 10 mm to 100 mm; the heating temperature of the heating element 1 is set to a temperature range that enables the above-mentioned technical effects, which is 50°C to 300°C.

[0028] Gradient heating using multiple tandem heaters (1a, 1b, 1c) allows for expansion to support different path lengths, heating modes, and temperature gradients, making it widely adaptable to various mass spectrometry platforms and enhancing versatility. The temperature gradient can be set to a low-temperature front and a high-temperature rear. Multiple tandem heaters can include two or three, which can be configured according to the specific mass spectrometer, ensuring maximum ion exposure during desolvation and improving ionization efficiency.

[0029] like Figure 2As shown, the heating element 1 is disc-shaped and includes a main body 10. The main body 10 has a first end face A corresponding to the ion outlet of the nozzle 5 and a second end face B corresponding to the ion inlet of the mass spectrometer 6. The ion inlet 110 of the ion transmission channel 101 protrudes from the first end face A, and the ion outlet 120 of the ion transmission channel 101 protrudes from the second end face B. This not only facilitates precise alignment with the ion outlet of the nozzle 5 of the nano-electrospray source 4 and the ion inlet of the mass spectrometer 6 during installation, but also enables it to be as close as possible to the ion outlet of the nozzle 5 of the nano-electrospray source 4 and the ion inlet of the mass spectrometer 6, thus accommodating more ions.

[0030] In this design, the ion inlet 110 of the ion transmission channel 101 is positioned at a distance of 0.5-5 mm from the ion outlet of the nozzle 5. By placing a heater 1 near the ion outlet of the nozzle 5, the thermal drying problem that might occur at the ion inlet of the mass spectrometer 6 due to excessive temperature on the nozzle 5 can be avoided. Simultaneously, the spatial path of ion atomization can be appropriately heated, accelerating the solvent removal process of solvent-laden ion clusters. This ensures that ions are exposed before the ion clusters enter the sample inlet of the mass spectrometer 6, thereby effectively improving solvent removal efficiency, enhancing signal response, and reducing background noise.

[0031] like Figure 1 As shown, the support body 2 adopts a sealed cover, which is configured to cooperate with the mass spectrometer 6 to fix and shield the ion inlet of the mass spectrometer 6. Ion transmission channel 101 (as shown) Figure 2 The ion outlet (shown) is connected to the enclosure space of the sealing cover. The opening of the sealing cover is flared towards the ion inlet of the mass spectrometer 6. The sealing cover can isolate the dangerous voltage and high temperature at the sample inlet of the mass spectrometer 6, protecting the operator's safety, and can also support the heating element 1. Of course, the support body 2 can also be other components that support the heating element 1 at a certain height, which is not limited here.

[0032] like Figure 2 As shown, the heating device also includes a heating element 13 and a temperature control element 14 disposed on the heating body 1, and a controller (not shown) connecting the heating element 13 and the temperature control element 14. The heating body 1 may be made of metal materials such as stainless steel or aluminum; the heating element 13 may be made of high-temperature resistant materials, such as ceramic materials, etc. The temperature of the heating body 1 is increased by heating the heating element 13; the temperature value is read by the temperature control element 14.

[0033] like Figure 1As shown, the heating device also includes a connector 3 that connects and positions the nano-electrospray source 4 and the mass spectrometer 6. The connector 3 ensures a stable connection between the nano-electrospray source 4 and the mass spectrometer 6, preventing movement between them. The connector 3 includes a first connector 31 connected to the nano-electrospray source 4 and a second connector 32 connected to the mass spectrometer 6. The first connector 31 and the second connector 32 are interlocked and locked together by a connector 33.

[0034] The heating device in this application embodiment is applicable to a variety of ion sources, including but not limited to nanoESI, microESI, DESI, nanoDESI, DISI, SICRIT, and LESA, and adopts a modular design that is ready to use out of the box. It can be adapted to various models of liquid chromatography-mass spectrometry (LC-MS) systems from different manufacturers.

[0035] like Figures 4-6 The mass spectrometry device 100 with nanoliter electrospray source provided in the embodiments of this application is used to detect organic small molecule samples (oils). Figure 4 The demonstration shows that two oil samples were input into the mass spectrometer 6 via nanoliter electrospray source 4 during two time periods (0.849-1.503 minutes and 3.451-4.263 minutes). Figure 5 The study showed that ion signals were detected between 3.451 and 4.263 minutes. Figure 6 The demonstration showed that ion signals were detected within 0.849-1.503 minutes. Therefore, the nano-electrospray source mass spectrometry device 100 provided in this application embodiment, after adopting a heating device, can be effectively adapted to the mass spectrometer 6, enabling effective detection by the mass spectrometer 6.

[0036] In the description of this application, it should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", "axial", "radial", "circumferential", etc., indicating the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, are only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of this application.

[0037] Furthermore, the terms "first," "second," etc., are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Therefore, a feature defined with "first," "second," etc., may explicitly or implicitly include at least one of those features.

[0038] In the description of this application, "multiple" means at least two, such as two, three, etc., unless otherwise expressly and specifically limited.

[0039] In this application, unless otherwise expressly specified and limited, the terms "installation," "connection," "joining," "fixing," etc., should be interpreted broadly. For example, "connection" can be a fixed connection, a detachable connection, or an integral part; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium; it can be the internal communication of two components or the interaction between two components, unless otherwise expressly limited. Those skilled in the art can understand the specific meaning of the above terms in this application according to the specific circumstances.

[0040] In this application, unless otherwise expressly specified and limited, "above" or "below" the second feature can mean that the first and second features are in direct contact, or that the first and second features are in indirect contact through an intermediate medium. Furthermore, "above," "over," and "on top" of the second feature can mean that the first feature is directly above or diagonally above the second feature, or simply that the first feature is at a higher horizontal level than the second feature. "Below," "below," and "under" the second feature can mean that the first feature is directly below or diagonally below the second feature, or simply that the first feature is at a lower horizontal level than the second feature.

[0041] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of this application. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0042] The above description is merely a preferred embodiment of this application and is not intended to limit the scope of protection of this application. Any equivalent substitutions, modifications, or improvements made by those skilled in the art to this application without departing from the spirit and scope of this application shall fall within the scope of protection of this application.

Claims

1. A heating device, characterized in that, A heating device, positioned between the nano-electrospray source and the mass spectrometer, is arranged along the direction of the atomized ion ejection from the nano-electrospray source. Supporting entity; A heating element, disposed on the supporting body, is used to apply heat to the ion transport path and is provided with an ion transport channel for ions or charged droplets to pass through; the ion inlet of the ion transport channel corresponds to the ion outlet of the nanoliter electrospray source, and the ion outlet of the ion transport channel corresponds to the ion inlet of the mass spectrometer.

2. The heating device according to claim 1, characterized in that, The ion inlet of the ion transport channel of the heating element is configured such that the distance between the ion inlet and the ion outlet of the nano-electrospray source is between 0.5 and 5 mm.

3. The heating device according to claim 1, characterized in that, The heating element may be one or more connected in series; The heating temperature of the multiple series-connected heating elements is set to form a gradient change in the direction from the ion outlet toward the ion inlet of the mass spectrometer.

4. The heating device according to claim 1, characterized in that, The length of the ion transport channel of the heating element is set to a range that allows the charged droplets formed by nano-electrospray to be fully desolventized and maintain spray stability before entering the mass spectrometer, and the length range is 5 mm to 30 mm. When multiple heating elements are connected in series, the total length of their corresponding ion transmission channels is set to a length range that can achieve the above-mentioned technical effects, preferably 10 mm to 100 mm; the heating temperature of the heating elements is set to a temperature range that can promote droplet desolvation, reduce solvent cluster coalescence, and improve ion signal stability, wherein the temperature range is 50°C to 300°C.

5. The heating device according to claim 1, characterized in that, The support body adopts a sealing cover, which is configured to cooperate with the mass spectrometer to fix and shield the ion inlet of the mass spectrometer; The ion outlet of the ion transport channel is connected to the covering space of the sealing cover.

6. The heating device according to claim 5, characterized in that, The opening of the sealing cover is flared outwards, facing the ion inlet of the mass spectrometer.

7. The heating device according to any one of claims 1-6, characterized in that, The heating element includes a body, which has a first end face corresponding to the ion outlet of the nanoliter electrospray source and a second end face corresponding to the ion inlet of the mass spectrometer. The ion inlet of the ion transport channel protrudes from the first end face, and the ion outlet of the ion transport channel protrudes from the second end face.

8. The heating device according to any one of claims 1-6, characterized in that, It also includes a heating element and a temperature control element disposed on the heating body, and a controller connected to the heating element and the temperature control element.

9. The heating device according to any one of claims 1-6, characterized in that, It also includes a connector for connecting and positioning the nanoliter electrospray source and the mass spectrometer; The connector includes a first connector connected to the nanoliter electrospray source and a second connector connected to the mass spectrometer. The first connector and the second connector are plugged into each other and locked by a connector.

10. A mass spectrometry device with a nanoliter electrospray source, characterized in that, include: A nanoliter electrospray source and a mass spectrometer; the nanoliter electrospray source is configured to spray mist-like ions, and the mass spectrometer is configured to receive the mist-like ion signal; The mass spectrometry device of the nano-electrospray source further includes a heating device as described in any one of claims 1-9, disposed between the nano-electrospray source and the mass spectrometer along the direction of the atomized ion ejection.

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