Deposit reduction ionization source

Abstract

A deposit reduction ionization source for introducing a sample to a mass spectrometer is provided. The deposit reduction ionization source includes a heating vessel having a set of circulating hot gases to avoid any condensation formation within the volume of the vessel to maintain the vessel clean. The container has a tubular cross-section with a conduit attached to its side wall. The container is placed in front of the orifice of the curtain cone. An exhaust port is located on an opposite side of the conduit on the wall and proximate to the curtain cone. An atomizer is placed inside the conduit. Atomizing gas and auxiliary gas are introduced into the conduit and curtain gas is introduced into the curtain cone.

Description

Technical Field

[0001] This invention generally relates to atmospheric pressure ionization sources for mass spectrometry, and more specifically to systems for reducing contamination in ion sources and ion introduction systems. Background Technology

[0002] Mass spectrometry (MS) is used to determine molecular weight and structural information about compounds. Molecules are weighed by ionizing them and measuring their response to electric and magnetic fields in a vacuum. Ions are weighed based on their mass-to-charge ratio (m / z). Typically, sample analysis consists of sample introduction, ion source, ion separation, and ion detection, with sample introduction and ion source being the most critical steps. The sensitivity of a mass spectrometer depends in part directly on the efficiency of the ion source in producing a high yield of the desired ions of interest.

[0003] In atmospheric pressure mass spectrometry (APMS), there are three main types of sources. Typically, primary ions are formed by gas discharge induced by an electric field or electrospray ionization (ESI) at atmospheric pressure. These primary ions then ionize the gaseous analyte molecules through ion-molecule processes (such as charge transfer processes in atmospheric pressure chemical ionization (APCI)) or by entraining analyte molecules in charged solvent droplets generated during electrospray ionization. In the case where the analyte is entrained in a charged droplet, the ionization process is the same as in ESI, because the analyte molecules are first entrained in the droplet and subsequently ionized.

[0004] Electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) are the most widely used ionization techniques in modern mass spectrometry. In both of these ionization methods, the ionization process takes place at or near atmospheric pressure. Atmospheric pressure photoionization (APPi) has also been developed for the ionization of certain compounds. At atmospheric pressure, all ionization techniques share a major advantage over other techniques: the ionization process is gentle, and the molecule of interest is ionized at its fundamental energy level. This is an important characteristic that preserves the integrity of the compound's molecular structure.

[0005] In typical atmospheric ionization, a solution is injected through a needle under high pressure. The needle diameter is typically about 0.01 mm or 0.2 mm. The high-pressure injection of the polar liquid produces a small plume or mist of droplets. This plume may contain the sample and a buffer solution. The buffer is typically a mixture of water, alcohol, or any other material. A voltage (typically 4000-6000 V) is applied to the needle to generate charged droplets. The charged droplets undergo charge separation at the needle tip. The plume is then injected into a source housing containing similar charged droplets. Sometimes heat is introduced to desolvate the plume and evaporate the material, thus converting the plume into a gas phase, which partially passes through the sample inlet orifice into the mass spectrometer. In all these systems, the entire source is contained within a source housing.

[0006] In many systems, the sample inlet orifice is located behind an orifice called a curtain cone, near the plume. A cleaning gas (curtain gas) is introduced between these two orifices to prevent unwanted substances from entering the mass spectrometer and to aid in the desolvation of the nebulizer plume. In the case of ESI, a high voltage is applied to the emitter, causing the polarized sample to undergo charge separation at the tip of the nebulizer emitter. Depending on the polarity of the applied voltage, ions with opposite charges generated at the emitter tip return to the emitter and are neutralized. Other charge types are generally repelled by the voltage and move toward the sample inlet orifice of the MS. The nebulizer plume, which is partly liquid and partly gaseous, often condenses on the inner wall of the ionization housing, resulting in sample residue. Over time, this condensation accumulates and leads to cross-contamination, thus requiring frequent cleaning to avoid cross-interference with subsequent samples.

[0007] In many mass spectrometers, an ESI or APCI, or both, is positioned in front of the mass spectrometer and enclosed in a container for safety and to prevent air molecules from entering the container. In most cases, the nebulizer plume is accompanied by nebulizer gas and auxiliary heat to provide further desolvation of the plume. Moreover, auxiliary heating is crucial in high-flow-rate liquid chromatography (LC) to aid desolvation and thus improve the sensitivity of the instrument.

[0008] In the current system, the spray plume and auxiliary heating cause the liquid containing the buffer and sample to evaporate. The vapor disperses into the surrounding environment and condenses on the inner surface of the housing containing the ionization source. This leads to interference with the detection of the sample of interest (cross-contamination) and requires frequent cleaning, resulting in reduced uptime of the mass spectrometry device.

[0009] One of the main challenges in modern mass spectrometry is maintaining source cleanliness. Sources must be kept clean to function properly. The inner surfaces of atmospheric pressure ionization sources are particularly susceptible to this type of contamination because they are frequently exposed to aerosol samples during operation, which typically include non-volatile compounds. The accumulation of sample matrix components on the inner surfaces of the source can lead to decreased MS sensitivity. As previously mentioned, some of the plume may condense around the housing of the apparatus as it cools. This can alter the properties of subsequent samples introduced into the system. If some of the first sample is concentrated and remains inside the source housing, it will contaminate the second sample.

[0010] Conventional methods for removing contaminants typically involve removing or disassembling the contaminated ion source, followed by manual cleaning. Subsequently, the mass spectrometer may need to be recalibrated after the ion source is put back into service. Therefore, such manual cleaning is time-consuming and resource-intensive, and furthermore, it is impractical given the potential for rapid contaminant accumulation. Summary of the Invention

[0011] This invention discloses a sample introduction system that limits the accumulation of any material in the ionization source and introduction region. The system comprises a heated container placed in front of a mass spectrometer (MS). The container has several gas flows configured to create a set of circulating zones within the container and confine ions to a central region of the heated container. The container has a right side, left side, top side, and bottom side. A heater is used to heat the heated container to prevent condensation on its surface and to maintain the gas inside the container at a high temperature. A conduit is attached to the top side of the heated container. An nebulizer with an atomizer tip is placed inside the conduit. The atomizer tip is positioned in a predefined location, either inside the conduit or penetrating into the heated container. A nebulizing gas with an atomizer gas flow rate and temperature is used in the nebulizer to form a nebulized sample from the sample. A heating auxiliary gas with an auxiliary flow rate and temperature is introduced into the conduit surrounding the nebulizer and the nebulizing gas. A curtain cone, which may be an interface to the MS or part of a separate interface, is placed on the right side of the heated container. The curtain cone has an orifice that allows ions to flow out of the container and into the MS. Heated curtain gas with a curtain flow rate and temperature is introduced into the curtain cone. The curtain gas enters the heating container from the right side. The exhaust port is located on the bottom side of the container, near the right side. A pump is connected to the exhaust port to form an exhaust flow. The pump causes the exhaust flow rate to be at which the heated container exits. One or more ionization sources may be attached to the container and may operate together or sequentially. The ionization sources are placed inside the conduit or on the right side or bottom of the heating container to ionize the nebulized sample and form ions. The nebulizer gas flow rate and temperature, the auxiliary flow rate and temperature, the curtain gas flow rate and temperature, and the exhaust flow rate are configured to confine the ions to the central region of the heating container and away from the walls of the heating container. These flows result in a circulating flow of heated gas within the heating container to keep the container clean. The electric field inside the container guides the ions from the central region to the orifice of the curtain cone and then to the mass spectrometer.

[0012] According to the present invention, a sediment reduction system for mass spectrometry is provided, the sediment reduction system comprising: a heating container mounted in front of a sample introduction system of a mass spectrometer (MS); a heater configured to heat the heating container; a conduit attached to the heating container; a nebulizer configured to introduce atomizing gas having a nebulizer gas flow rate and a temperature; a sample introduction device having a sample introduction tip configured to introduce a sample into the heating container through the sample introduction tip, wherein the sample introduction tip is placed inside the conduit or inside the heating container; the nebulizer and the sample introduction device are configured such that the nebulizing gas mixes with the sample at the sample introduction tip to form a mixture of nebulizer gas and the sample at the sample introduction tip; and wherein the nebulizer gas flow rate is at least about 0.8 + / - 10% Mach.

[0013] In one aspect of the invention, the sediment reduction system for mass spectrometry further comprises: a heating auxiliary gas having an auxiliary gas flow rate and a temperature, the heating auxiliary gas being introduced into a heating container via a conduit and configured to surround an atomizing gas; a curtain cone interfacing with the MS sample introduction system via an orifice, the curtain cone being located within the heating container; a heating curtain gas having a curtain gas flow rate and a temperature, the heating curtain gas being introduced between the curtain cone and the orifice; a heating container having an exhaust port connected to a pump, the pump being configured to form an exhaust flow having an exhaust flow rate from the heating container; a first ionization device configured to ionize a sample and form a mixture of the atomizing gas and ions; and wherein the atomizing gas flow rate and temperature, the auxiliary flow rate and temperature, the curtain gas flow rate and temperature, and the exhaust flow rate are configured to guide the ions away from the wall of the heating container.

[0014] In another aspect of the invention, the nebulizer gas flow rate of the sediment reduction system for mass spectrometry is about 1.0 + / - 10% Mach or higher. In another aspect, the sediment reduction system for mass spectrometry further comprises: a sample introduction device with a voltage-equipped tip; a curtain cone with a voltage lower than the tip; and an orifice with a voltage lower than the curtain cone. In yet another aspect of the invention, the sediment reduction system for mass spectrometry further comprises: an orifice with a voltage-equipped tip; a curtain cone with a voltage lower than the orifice; and a sample introduction device with a voltage lower than the tip of the curtain cone.

[0015] In another aspect of the invention, the sediment reduction system for mass spectrometry further comprises: a tip, a curtain cone, and an orifice of a sample introduction device for forming a voltage gradient, wherein the system is configured to allow an operator to switch between a positive and a negative voltage gradient. In another aspect of the invention, the sediment reduction system for mass spectrometry has a first ionization device, which is one of: (i) an electrospray device, (ii) an atmospheric pressure chemical ionization (APCI) device, or (iii) an atmospheric pressure photoionization (APPI) device. In another aspect of the invention, the sediment reduction system for mass spectrometry has an auxiliary gas moving in laminar flow and a mixture of atomizing gas and ions.

[0016] In another aspect of the invention, the sediment reduction system for mass spectrometry has a heating container heated to at least about 500 + / - 10°C. In another aspect of the invention, the heating container is tubular and has a cross-sectional shape selected from the group consisting of circular, elliptical, oval, and polygonal shapes. In yet another aspect of the invention, the heating container has a circular cross-sectional shape with a diameter of about 45 + / - 10% mm and a length of about 75 + / - 10% mm. In yet another aspect of the invention, the dimensions of the heating container are suitable to be in the range of about 50 + / - 10% mm by about 50 + / - 10% mm by about 80 + / - 10% mm. In yet another aspect of the invention, the sediment reduction system for a mass spectrometer further includes a second ionization device, and the first and second ionization devices are configured to operate simultaneously or alternately within the heating container.

[0017] This system provides a confined deposition ionization source in which different ionization sources can be implemented, either together or sequentially, thereby reducing the need for removal, disassembly, and manual cleaning of the system. Furthermore, this system allows the use of different ionization sources installed and calibrated sequentially without requiring recalibration of the system. This system saves time and resources and provides more efficient operation of the mass spectrometer. Attached Figure Description

[0018] The embodiments described below will be described in conjunction with the accompanying drawings, which are provided for illustration and not for limiting the scope of the claims, wherein similar names refer to similar elements, and in the drawings:

[0019] Figure 1 The first embodiment of the present invention is shown.

[0020] Figure 2 A second embodiment of the present invention is shown.

[0021] Figure 3 A third embodiment of the invention is shown, and

[0022] Figure 4 The fourth embodiment of the present invention is shown. Detailed Implementation

[0023] Most sample introduction systems consist of a container in which a spray plume is introduced and evaporated by a heated auxiliary gas. The container is placed near the orifice of the curtain cone to introduce ions into the mass spectrometer. A problem with this type of setup is that it is difficult to control the sample's trajectory while it is inside the container. Although some of the sample flows to the MS, some may remain on the container's surface and cause contamination problems in subsequent tests.

[0024] This system is configured to confine the sample and ions to the central region of the container and prevent them from impacting the container walls. This is achieved by creating a circulating flow field inside the container that continuously removes material from the container surface. In this system, a heating container 200, consisting of small hollow tubes, is placed in front of the sample introduction of the MS device. The heating container can be tubular and can have a circular, elliptical, oval, polygonal, or any other cross-sectional shape. In a preferred embodiment, the heating container has a circular cross-sectional shape with a diameter of about 45 mm and a length of about 75 mm. In another embodiment, the heating container has a tubular shape with a circular, elliptical, oval, or polygonal cross-section, the cross-section being suitable for a size range of about 50 mm by about 50 mm by about 80 mm. In this section, "about" means ±10%.

[0025] To describe the positioning of the different systems relative to the heating container, the sides of the container are named top side 201, bottom side 202, left side 203, and right side 204, as follows: Figure 1 What is shown.

[0026] The right side 204 forms the curtain cone of the MS device 290. In other embodiments, the curtain cone may exist as part of the MS interface, or the curtain cone may be a separate unit. The curtain cone has a sampling orifice 205 to receive ions and curtain gas 206, a portion of which enters the heating container at the sampling orifice 205.

[0027] exist Figure 1In this embodiment, the heating container has a conduit 210 attached to the top side of the container 200. The conduit is configured to receive an nebulizer 220. The nebulizer 220 has an nebulizer tube 221. The conduit 210 is also configured to receive a sample inlet tube 1000 for the sample 1010. In a preferred embodiment, the nebulizer 220 is configured to include the sample inlet tube 1000. The sample inlet tube 1000 has a sample inlet tip 222. Atomizing gas 225 passes through the nebulizer tube 221 and mixes with the sample 1010 at the sample inlet tip 222 to form an atomized sample 226. The nebulizer can be a separate unit or an electrospray ionization (ESI) system. When the atomizing gas 225 mixes with the sample 1010 at the tip 222, the flow rate of the atomizing gas 225 is at least about Mach 0.8. In a preferred embodiment, the flow rate of the atomizing gas is at least about Mach 1. In this context, about means ±10%.

[0028] Although the conduit 210 is preferably attached to the top side of the heating container 200, the conduit 210 may also be attached to either side of the heating container 200.

[0029] A heating assist gas 230 is also introduced into the conduit 210 to surround the nebulizing gas and the nebulized sample 226. The heating assist gas confines the nebulizing gas and the nebulized sample to the core region of the container. An ionization source, such as an ESI 220 (also used as a nebulizer), also placed in the conduit, provides ions confined to the central region of the container. The ESI can operate in both microfluidic and nanofluidic modes.

[0030] Container 200 also has a vent 240, which is preferably located on the bottom side 202 of container 200 and closer to the right side 204. The vent is connected to a pump (not shown) to drain the contents of the container. Although the vent 240 is preferably located on the bottom side 202 of container 200, it can be located on any wall of container 200 by using a suitable pump.

[0031] The auxiliary gas 230, atomizing gas 225, curtain gas 206, and exhaust port 240 are configured to form a circulating flow within the heating container 200, such as Figure 1 The ions 1, 2, 3, and 4 in the diagram are positioned to contain the ions of the atomized sample within the core and central region of the heating container, away from the walls of the heating container 200. These gases are heated in the same way as the container, thus preventing condensation and any contamination on the walls. Additionally, the circulating flow continuously cleans the surfaces to reduce the accumulation of any contaminants. Under the influence of the electric field between the ionization region and the MS, the ions 229 in the container travel towards the outlet orifice 205 and reach the MS 290.

[0032] The container is heated using heater 209 to maintain the gas within the container at a high temperature, preferably above about 100°C and below about 1000°C, where approximately means ±10%. In a preferred embodiment, the container is heated to about 500°C, where approximately means ±10%. Those skilled in the art will appreciate that these temperatures can be selected to optimize the analysis of a particular sample by MS. The auxiliary gas 230 can be heated before injection or can be heated inside the container. When the nebulizer is placed inside the conduit, the auxiliary gas is heated to create a volatilization zone inside the conduit. When the tip of the nebulizer is inside the container, volatilization occurs inside the container, and the hot gas inside the container helps to volatilize the sample. The container 200 is always maintained at a high temperature, thereby preventing any cold zones from forming inside the container, and therefore, no condensate will be deposited on the container walls.

[0033] The container can use different ionization systems. In one embodiment, the APCI 250 is positioned on the left side via insulator 251, while the ESI 220 (also an atomizer) is placed in the conduit with its tip positioned inside the container. Temperature and flow rate are adjusted for better desolvation and to prevent condensation. By waiting an appropriate period of time before the next sample introduction (typically with the exhaust pump always running), all residual gas and sample are pumped out, preventing any cross-contamination.

[0034] In such Figure 2 In another embodiment shown, APPi 340 is positioned on the left. ESI 320 with nebulizing gas 325 is positioned inside the conduit. Sample inlet tube 2000 and sample inlet tip 322 are also inside the conduit. When the nebulizing gas 325 mixes with the sample 2010 at tip 322, the velocity of the nebulizing gas 325 is at least about Mach 0.8. In a preferred embodiment, the velocity of the nebulizing gas is at least about Mach 1. In this context, about means ±10%.

[0035] A heating auxiliary gas 330 surrounds ions 326 inside the conduit, where partial volatilization occurs inside the conduit, and the ions are confined to the central region 20 of the container. Circulation zones 11 and 12 and an exhaust flow 15 generated by a pump connected to outlet 340 confine the ion flow to region 20, while an electric field force from the ionization zone to the MS directs the ions to orifice 305 and guides them into the MS.

[0036] In such Figure 1 In the first embodiment of the device shown, the atomizer (or ESI) 220 and APCI 250 are placed in a container, while... Figure 2In the second embodiment shown, a combination of an APPi 340 and an atomizer (or ESI) 320 is used within a container. The atomizer 320 is placed within a conduit. A spray plume 326 containing the sample is introduced into the conduit. The atomized sample evaporates and is delivered to a heated container via the atomizer 325 and a heated auxiliary gas 330. The geometry of the evaporation zone (i.e., the length and diameter of the conduit) is configured to produce laminar flow. The formed particles are entrained in the laminar flow and efficiently delivered to the heated container. The APPi 340 needs to evaporate before ionization. The temperature can be adjusted to optimize ionization (from the perspective of better MS detection), thereby improving desolvation and preventing condensation. This system allows access to both ESI and APPi in a single source, and therefore, the sample introduction system can be reconfigured without physical changes. This allows for a quick and easy switch from one ionization mode to another. Because both are placed within the system, the transition from ESI to APPi applications is straightforward.

[0037] By waiting an appropriate period of time before the next sample introduction (usually with the exhaust pump always running), all residual gas and sample are pumped out, thus preventing any cross-contamination.

[0038] exist Figure 3 In the third embodiment shown, a combination of ESI 420 and APCI 450 is used in a single source. The ESI 420 is placed inside the conduit, with its tip generating an atomized sample within the conduit. The atomized sample undergoes evaporation inside the conduit. The APCI 450 is placed on the left side of the container. Ionized material from the ESI 420 advances through this area and is introduced into the container. The temperature is adjusted for better desolvation and to prevent condensation. This allows access to both ESI and APCI in a single source. By waiting an appropriate period of time before the next sample introduction (typically with the exhaust pump always running), all residual gases and sample are pumped out, preventing any cross-contamination.

[0039] In such Figure 4 In the fourth embodiment shown, a combination of ESI 520, APCI 550 and APPi 540 is used in one container, and the operation of the system can be switched from one to the other without any cross-contamination (assuming that all residual gas and proper pumping out of the sample will be pumped out by waiting for an appropriate period of time before the next sample introduction, thus preventing any cross-contamination).

[0040] A spray plume 526 containing the sample is injected into the evaporation zone. ESI ions are delivered into the heated container via the flow of atomizer gas 525 and auxiliary gas 530.

[0041] Those skilled in the art will recognize that these methods can be used for any ionization device operating in an atmospheric environment.

[0042] In all embodiments, an electric field can be formed inside the container to direct ions toward the sampling orifice. For example, in the case of ESI ions, a corona discharge needle can be used by applying an appropriate voltage to create an electric field that helps ions migrate toward the sampler. The formation of three-dimensional or more fields within the container allows ions generated from any ionization mode (ESI, APCI, APPi, or any other ionization mode in the atmosphere) to be aggregated and directed toward the sampling orifice for better sensitivity of the MS device, regardless of the ionization mode.

Claims

1. A sediment reduction system for mass spectrometry, the sediment reduction system comprising: A heating container, which is mounted in front of the sample introduction system of a mass spectrometer (MS); A heater configured to heat the heating container; A conduit, which is attached to the heating container; An atomizer configured to introduce an atomizing gas, wherein the atomizing gas has an atomizer gas flow rate and a temperature; A sample introduction device having a sample introduction tip, the sample introduction device being configured to introduce a sample into the heating container through the sample introduction tip, wherein the sample introduction tip is placed inside the conduit or inside the heating container; The atomizer and the sample introduction device are configured such that the atomizing gas mixes with the sample at the sample introduction tip to form a mixture of atomizer gas and the sample at the sample introduction tip; The atomizer gas flow rate is at least about 0.8 + / - 10% Mach.

2. The sediment reduction system for mass spectrometry according to claim 1, further comprising: A heating auxiliary gas having an auxiliary gas flow rate and a temperature, the heating auxiliary gas being introduced into the heating container through the conduit and configured to surround the atomizing gas; A curtain cone, which interfaces with the sample introduction system of the MS through an orifice, and the curtain cone is located in the heating container; Heated curtain gas, the heated curtain gas having a curtain gas flow rate and a temperature, the heated curtain gas being introduced between the curtain cone and the orifice; The heating container has an exhaust port connected to a pump, and the pump is configured to form an exhaust flow with an exhaust velocity flowing out of the heating container; A first ionization device is configured to ionize the sample and form a mixture of atomized gas and ions; The atomizer gas flow rate and temperature, the auxiliary flow rate and temperature, the curtain gas flow rate and temperature, and the exhaust flow rate are configured to guide the ions away from the wall of the heating container.

3. The deposition reduction system for mass spectrometry according to claim 1, wherein the atomizer gas flow rate is about 1.0 + / - 10% Mach or higher.

4. The sediment reduction system for mass spectrometry according to claim 2, further comprising: The sample introduction device has a voltage-equipped tip; The voltage is lower than that of the curtain cone at the tip; and The voltage is lower than the orifice of the curtain cone.

5. The sediment reduction system for mass spectrometry according to claim 2, further comprising: The orifice is subject to voltage; The voltage is lower than that of the curtain cone at the orifice; and The voltage of the sample introduction device is lower than that of the tip of the curtain cone.

6. The sediment reduction system for mass spectrometry according to claim 3, further comprising the tip, the curtain cone, and the orifice of the sample introduction device for forming a voltage gradient, wherein the system is configured to allow an operator to switch between a positive voltage gradient and a negative voltage gradient.

7. The sediment reduction system for mass spectrometry according to claim 6, wherein the first ionization device is one of: (i) an electrospray device, (ii) an atmospheric pressure chemical ionization (APCI) device, or (iii) an atmospheric pressure photoionization (APPI) device.

8. The sediment reduction system for mass spectrometry according to claim 7, wherein the auxiliary gas and the mixture of atomizing gas and ions move in laminar flow.

9. The sediment reduction system for mass spectrometry according to claim 8, wherein the heating container is heated to at least about 500 + / - 10% °C.

10. The sediment reduction system for mass spectrometry according to claim 5, wherein the heating container is tubular and the heating container has a cross-sectional shape selected from the group consisting of: circular, elliptical, oval, and polygonal shapes.

11. The sediment reduction system for mass spectrometry according to claim 10, wherein the heating container has a circular cross-sectional shape and a diameter of about 45 + / - 10% mm and a length of about 75 + / - 10% mm.

12. The sediment reduction system for mass spectrometry according to claim 10, wherein the size of the heating container is suitable in the size range of about 50 + / - 10% mm by about 50 + / - 10% mm by about 80 + / - 10% mm.

13. The sediment reduction system for a mass spectrometer according to claim 11, further comprising a second ionization device, wherein the first ionization device and the second ionization device are configured to operate simultaneously or alternately within the heating container.

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