Electrospray probe

Abstract

Disclosed is an electrospray probe for an electrospray ion source, the electrospray probe comprising a sleeve extending from a proximal end having an inlet aperture for receiving a liquid sample containing at least one analyte to a discharge emitter end having an outlet aperture through which charged droplets containing ions of the analyte are discharged, and a conductive coating covering at least a portion of an outer surface and at least a portion of an inner surface of the emitter end.

Description

[0001] Related Applications

[0002] This application claims priority to provisional patent application entitled“Electrospray Probe” and having application number 62 / 855,606, filed May 31, 2019, which is incorporated by reference herein in its entirety. TECHNICAL FIELD

[0003] The present disclosure relates generally to an electrospray emitter for use in a mass spectrometer, and more particularly to an electrospray emitter for generating ions in an atmospheric pressure ionization source of a mass spectrometer. BACKGROUND

[0004] Mass spectrometry (MS) is an analytical technique used to measure the mass-to-charge ratio of molecules within a sample, with both qualitative and quantitative applications. MS can be used to identify unknown compounds, determine the isotopic composition of elements in a molecule, determine the structure of a particular compound by observing its fragments, and quantify the amount of a particular compound in a sample. Mass spectrometers detect chemical entities as ions, such that a conversion of the analyte to a charged ion must occur prior to the sampling process. Due to the accuracy and sensitivity requirements of most MS applications, complex samples are often subjected to a separation technique prior to ionization.

[0005] Over the years, various sampling techniques have been developed to convert chemical entities in a liquid sample into charged ions suitable for detection with MS. One of the more common ionization methods is electrospray ionization (ESI) (e.g., pneumatic assisted electrospray, nanoelectrospray), due to its ability to perform functions such as transferring molecules including macromolecules from solution as intact, multiply charged molecular ions into the gas phase, and its ease of coupling to various sample sources including liquid chromatography and capillary electrophoresis.

[0006] A typical electrospray emission process can occur when the electrostatic forces on the surface of a liquid sample overcome the surface tension. Specifically, in a typical ESI process, a liquid sample is discharged through an electrically conductive needle, electrospray electrode, or nozzle into an ionization chamber while a potential difference between the electrospray electrode and a counter electrode creates a strong electric field within the ionization chamber that charges the liquid sample. This can cause a Taylor cone to form at or near the emitter tip of the electrospray electrode. A liquid jet can then be emitted from the apex of the Taylor cone. Specifically, if the charge applied to the surface of the liquid is strong enough to overcome the surface tension of the liquid (i.e., the particles attempt to disperse the charge and return to a lower energy state), the electric field generated within the ionization chamber causes the liquid discharged from the electrospray electrode, needle, or nozzle to disperse into a plurality of charged microdroplets that are attracted toward the counter electrode. As the solvent within the microdroplets evaporates during desolvation in the ionization chamber, the charged analyte ions can then enter a sampling orifice of the counter electrode for subsequent mass spectrometric analysis.

[0007] Applying high voltage conditions to a liquid sample can affect the ionization performance of an electrospray probe, particularly when operated in negative ion mode to produce negatively charged ions. When electrospraying samples prepared in acidified water in negative ion mode, the maximum ESI potential is often limited by the onset of corona discharge. When corona discharge onset occurs at a lower potential than the optimum spray potential, the analytical performance is reduced. While electrospray has been a very successful technique, there are limitations of conventional electrospray that can negatively impact the ability to obtain the desired sensitivity or accuracy for mass analysis.

[0008] Accordingly, there is a need for improved electrospray emitters and methods of ionizing a liquid sample. SUMMARY

[0009] In one aspect, an electrospray emitter for an electrospray ion source is disclosed, the electrospray ion source including an emitter including a sleeve extending from a proximal end having an inlet orifice for receiving a liquid sample containing at least one analyte to a distal end having an outlet orifice through which charged droplets of ions containing the analyte are discharged, and a conductive coating covering at least a portion of an outer surface and at least a portion of an inner surface of the emitter end.

[0010] In some embodiments, the emitter end has a rounded tip. As an example, the rounded tip can have a radius of curvature in a range of about 20 microns to about 200 microns, such as in a range of about 50 microns to about 150 microns. In some embodiments, the diameter of the outlet orifice of the emitter can be in a range of about 1 micron to about 150 microns. Preferably, the diameter of the outlet orifice can be in a range of about 5 microns to about 50 microns.

[0011] In some embodiments, the proximal end of the sleeve is configured for coupling to a liquid chromatography (LC) column to receive the liquid sample. In some embodiments, the sleeve has a stationary phase of the LC column, such as an ion exchange resin, disposed in a portion of the sleeve upstream of the outlet orifice. In some embodiments, different LC stationary phases, such as C18, can be disposed in one or more portions of the emitter.

[0012] In some embodiments, the sleeve can have an inner diameter in a range of about 5 microns to about 150 microns.

[0013] In some embodiments, the conductive coating can include any electrically conductive material. In some embodiments, the conductive coating can include a metallic material, such as titanium, platinum, gold, or silver. In other embodiments, the conductive coating can include an alloy. In some embodiments, the conductive coating can include multiple layers formed of different metallic materials. In some embodiments, the conductive coating has a thickness of about 50 Angstroms to about 5 microns. Such as in a range of 1 nm to about 1 micron.

[0014] In some embodiments, the sleeve is configured to accommodate a flow rate of a liquid sample in a range from about 1 nL / min to about 5 mL / min. As an example, the sleeve can be configured to accommodate a flow rate in a range from about 100 nL / min to about 2 μL / min (microliters / minute). In some such embodiments, the outlet aperture has a diameter in a range from about 10 microns to about 40 microns.

[0015] In related aspects, a mass spectrometer system is disclosed that includes an ion source having an electrospray probe for generating ions; a curtain plate having an aperture for receiving at least a portion of the ions; and one or more mass analyzers disposed downstream of the aperture of the curtain plate. The electrospray probe can include a sleeve extending from a proximal end having an inlet aperture for receiving a liquid sample containing at least one analyte to an outlet aperture through which charged droplets of ions containing the analyte are discharged. An electrically conductive coating covers at least a portion of an outer surface and at least a portion of an inner surface of the emitter end. In some embodiments, the emitter end can include a rounded tip. As an example, in some embodiments, the rounded tip can have a radius of curvature in a range from about 20 microns to about 200 microns. As an example, in some embodiments, the rounded tip can have a radius of curvature in a range from about 50 microns to about 100 microns.

[0016] The proximal end of the sleeve can be configured to be coupled to a liquid chromatography (LC) column to receive the liquid sample. Alternatively, one or more LC stationary phases can be packed into the sleeve of the emitter.

[0017] For example, in some embodiments, a stationary phase of an LC column (e.g., a C18 stationary phase, an ion exchange resin, or any other suitable stationary phase) can be disposed in a portion of the sleeve upstream of the outlet aperture.

[0018] In some embodiments of the mass spectrometer, the electrically conductive coating includes any electrically conductive material. In some embodiments, the electrically conductive coating includes a metallic material, such as titanium, platinum, gold, or silver. In other embodiments, the electrically conductive coating includes an alloy. In some embodiments, the electrically conductive coating has a thickness in a range from about 50 Angstroms to about 5 microns, such as in a range from about 1 nm to about 1 micron.

[0019] In some embodiments of the mass spectrometer, the sleeve can be configured to accommodate a flow rate of a liquid sample in a range from about 1 nL / min to about 5 mL / min, such as from about 100 nL / min to about 2 μL / min. In other embodiments, the sleeve can be configured to accommodate a flow rate of a liquid sample in a range from about 10 nL / min to about 1 μL / min. In some such embodiments, the outlet aperture has a diameter in a range from about 1 micron to about 150 microns. In other embodiments, the outlet aperture has a diameter in a range from about 10 microns to 40 microns.

[0020] Various different mass analyzers can be employed in the mass spectrometer described above. Some examples of such mass analyzers include, but are not limited to, any of a quadrupole mass analyzer, a time-of-flight (ToF) mass analyzer, an ion cyclotron resonance mass analyzer, or an Orbitrap mass analyzer, among others.

[0021] A detector can be disposed downstream of the mass analyzer for detecting ions and generating an ion detection signal. The analysis module can receive the ion detection signal and generate a mass spectrum of the ions.

[0022] In related aspects, a method for ionizing a sample is disclosed that includes providing an electrospray probe including a sleeve extending from a proximal end having an inlet orifice for receiving a liquid sample containing at least one analyte to a discharge emitter end having a discharge orifice through which charged droplets of ions containing the analyte are discharged, an electrically conductive coating covering at least a portion of an outer surface and at least a portion of an inner surface of the emitter end, maintaining the electrically conductive coating at an elevated electrical potential, introducing the liquid sample into the sleeve via the inlet orifice so as to provide a flow of the liquid sample from the inlet orifice to the discharge orifice, wherein the liquid sample is discharged via the discharge orifice as a plurality of charged droplets of ions containing the analyte. In some embodiments, the electrically conductive coating can be maintained at a voltage in a range of about 0 to about 7500 V to produce positive ions, and at a voltage in a range of about 0 to about (-7500 V) to produce negative ions. In some embodiments, the electrically conductive coating can be grounded, and a counter electrode can be held at a high electrical potential. For example, the electrically conductive coating can be grounded, and the counter electrode can be held at a high negative potential to produce positive ions, or the counter electrode can be held at a high positive potential to produce negative ions forming an ESI emitter.

[0023] A further understanding of the various aspects of the present teachings can be obtained by reference to the following detailed description, taken in connection with the accompanying drawings, in which: BRIEF DESCRIPTION OF DRAWINGS

[0024] Figure 1A is a partial schematic view of a tip of an emitter that can be used in an electrospray probe, in accordance with an embodiment,

[0025] Figure 1B is Figure 1A is another schematic view of an emitter showing an entry orifice and a discharge orifice of the emitter,

[0026] Figure 1C shows a mechanism for applying a high voltage to an electrically conductive coating at a tip of an emitter, in accordance with an embodiment of the present teachings,

[0027] Figure 2Ais a partial schematic view of a tip of an emitter according to an embodiment, wherein the tip of the emitter has a circular profile,

[0028] Figure 2B is Figure 2A is another schematic view of an emitter, showing an entry opening of the emitter as well as a discharge outlet,

[0029] Figure 3A is a schematic view of an emitter having a sharp tip,

[0030] Figure 3B is a schematic view of an emitter according to an embodiment having a tip with a circular profile,

[0031] Figure 3C is a schematic view of an emitter according to another embodiment having a tip with a circular profile having a different radius of curvature than Figure 3B

[0032] Figure 4 is an example of an electrospray probe according to an embodiment, wherein an emitter according to the present teachings is incorporated,

[0033] Figure 5 is another example of an electrospray probe according to another embodiment, wherein an emitter according to the present teachings is incorporated,

[0034] Figure 6 is schematically shown an example of a mass spectrometer wherein an electrospray probe according to an embodiment is incorporated,

[0035] Figure 7 is schematically shown an emitter according to an embodiment of the present teachings, the emitter comprising a sleeve, a stationary phase of an LC column being arranged in a portion of the sleeve,

[0036] Figure 8 are digital photographs showing emitters having different geometries, obtained during ESI (electrospray ionization) in negative ion mode, while spraying a sample comprising taurocholic acid (90% water and 0.1% formic acid),

[0037] Figure 9 are shown ion signals obtained using different electrospray emitters having different tip geometries, and

[0038] Figure 10 are shown results of simulations of the electric field strength at the tip of emitters having different geometries. DETAILED DESCRIPTION

[0039] ​The present disclosure relates generally to electrospray probes for use in mass spectrometry systems, and more particularly to such probes having emitters comprising tips coated with an electrically conductive material (e.g., a metal). As discussed in greater detail below, the electrically conductive coating can cover at least a portion of an outer surface and at least a portion of an inner surface of the emitter tip. Moreover, in many embodiments, the coated tip has a rounded rather than a tapered profile. Such emitters can be used in a variety of different electrospray probes, as discussed in greater detail below.

[0040] Various terms are used herein in accordance with their ordinary meanings in the art. As used herein, the term "about" denotes a deviation of at most 10% around a numerical value. As used herein, the term "substantially" denotes a deviation of less than 10% from a complete state and / or condition, if any.

[0041] Figure 1A and 1B A schematic view of an emitter 100 according to embodiments of the present teachings is shown, which can be incorporated in an electrospray probe of a mass spectrometry system, as discussed in greater detail below. The emitter 100 comprises a sleeve 200 extending from a proximal end 201 having an inlet aperture 201a for receiving a liquid sample containing or suspected of containing at least one analyte of interest to a discharge emitter end 202 having an outlet aperture 202a through which charged droplets containing analyte ions are discharged.

[0042] The sleeve 200 can be made of any suitable material known in the art. For example, the sleeve 200 can be formed as a single fused silica tube, or it can be formed from two or more separate portions that are coupled to one another to form the emitter. The electrically conductive coating 203 covers a portion 204a of an outer surface 204 of the emitter tip as well as a portion 205a of an inner surface 205 of the emitter tip 210. The electrically conductive coating can be formed from a variety of different electrically conductive materials. For example, in some embodiments, the electrically conductive coating can be formed from a metal, such as gold, silver, platinum, titanium, or any other metallic species. In some embodiments, the electrically conductive coating can be formed from an alloy. In some embodiments, the electrically conductive coating can comprise multiple layers, such as a titanium coating with a top platinum coating (e.g., in one such embodiment, the titanium coating can have a thickness of about 500 Angstroms and the platinum coating can have a thickness of 4000 Angstroms). In some embodiments, the electrically conductive coating can have a thickness in a range of, for example, about 5 Angstroms to about 5 microns, such as in a range of about 100 nm to about 1 micron, although other suitable thicknesses can also be utilized.

[0043] The inner conductive coating 205a extends into the inner surface of the sleeve 200. In some embodiments, the inner conductive coating can have a length (i.e., an axial extension parallel to the longitudinal axis of the emitter from the exit orifice to the end of the inner conductive coating) that is greater than the diameter of the exit orifice of the emitter. For example, the length of the inner conductive coating 205a can be at least about 3 times, or at least about 5 times, or at least about 10 times the diameter of the exit orifice of the emitter. In other words, the inner conductive coating can extend into the sleeve a distance that is greater than the diameter of the exit orifice, e.g., 3 times, 5 times, or 10 times the diameter of the exit orifice. As an example, the inner conductive coating 205a can have a length of about 60 microns, although other lengths can also be employed as described above.

[0044] As Figure 1A and 1B Illustratively, in this embodiment, the emitter tip 210 has a conical profile. As discussed in more detail below, in other embodiments, the emitter tip can have a circular profile.

[0045] Various mechanisms can be employed to apply a high voltage to the conductive coating at the emitter tip. For example, Figure 1C It is shown that the conductive coating can be directly coupled to a high voltage source. In other embodiments, a high voltage can be applied to the counter electrode to generate an electric field at the emitter tip for ionizing one or more analytes of a sample passing through the exit orifice of the emitter tip.

[0046] As noted above, in some embodiments, the conductively coated tip of the emitter can have a circular profile, rather than a conical profile. For example, with reference to Figure 2A and 2B Such an emitter 100' includes a sleeve 200' extending from a proximal end 201' having an inlet orifice 201a' for receiving a liquid sample containing or suspected of containing at least one analyte of interest to a discharge emitter end 202' having an exit orifice 202a' through which charged droplets containing analyte ions are discharged.

[0047] The conductive coating 203' covers a portion 204a' of the outer surface 204' of the emitter tip and a portion 205a' of the inner surface 205' of the emitter tip 210'. The sleeve 200' and the conductive coating 203' can have dimensions and can be formed of the same materials as related to the previous embodiments.

[0048] In contrast to the previous embodiments, the electrically conductive coating 203' has a rounded tip 210'. In other words, in contrast to the previous embodiments in which the emitter tip has a tapered profile, in this embodiment the tip 210' has a rounded profile. The rounded tip of the emitter can have a variety of different radii of curvature. For example, in some embodiments the rounded tip 210' can have a radius of curvature in the range of about 50 microns to about 100 microns.

[0049] By way of further illustration, Figure 3A An emitter is shown having a tapered sharp tip. In contrast, Figure 3B and 3C Two emitters having rounded tips according to this aspect of the present teachings are shown. Figure 3C The rounded tip of the emitter shown has a larger radius of curvature than Figure 3B The rounded tip of the emitter shown has a larger radius of curvature than

[0050] As discussed more in the Examples section below, it has been found that the rounded tip can improve and preferably eliminate the formation of a corona discharge when the emitter tip is held at a voltage required to ionize one or more analytes of a sample passing through the tip.

[0051] Emitters according to the present teachings can be incorporated into a variety of electrospray probes that can be employed in an ion source of a mass spectrometer.

[0052] By way of example, Figure 4 is a cross-sectional schematic view of an example of an electrospray probe 301 according to an embodiment in which an emitter according to the present teachings is incorporated.

[0053] In this embodiment, the electrospray probe 301 includes a probe body 398 having a channel 397 extending therethrough, into which a transmitter 300 according to embodiments of the present teachings, such as the transmitter 100 described above, can be installed. In this embodiment, the transmitter 300 includes a single piece of tubing having an internal lumen (also referred to herein as a channel, e.g., microchannel) that extends from its proximal end (also referred to herein as an inlet end) 327a (fluid connection end) to an ionization discharge end 310d, and out of the probe body 398 of the probe 301. The transmitter includes a segment 310 that terminates in a conductive-coated tip of the transmitter, near which ionization of the sample can occur, and a liquid conduit segment 320, which is formed using any suitable material, such as a fused silica tube or stainless steel. An insulating polymer, such as a PEEK polymer, can be molded or extruded onto the liquid conduit segment 320 of the transmitter 300. Molding or extruding a polymer onto the fused silica can be used to form a liquid connection to an LC column. Alternatively, a sleeve can be used to install the transmitter. The sleeve can be electrically conductive, electrically non-conductive, or partially electrically conductive. The transmitter 300 contains an axial depth positioning feature (positioning ring 330) that enables the user to accurately and simply install the transmitter tip. The positioning ring 330 can be secured in place with a positioning nut 350, as shown in Figure 4

[0054] The molded or extruded PEEK covered fused silica can provide the actual OD on the liquid conduit segment 320 for connection to an LC column and to receive a fluid sample. For example, in one aspect, the liquid conduit segment can provide a tube having an outer diameter (OD) of about 1 / 32 or 1 / 16 inch or in a range of about 150 pm to about 1.6 mm for connection to an LC column at the inlet end 327a of the transmitter 300. The fused silica or stainless steel tube can also provide the ID on the ionization discharge side 310d necessary to achieve sample electrospray. The ID at the ionization discharge end 310d can be, for example, from about 1 pm to about 300 pm.

[0055] The above-described electrospray probe 300 is provided as an example of an electrospray probe in which a transmitter according to the present teachings can be incorporated. However, it should be appreciated that the transmitter according to the present teachings can also be incorporated into other electrospray probes or nebulizer-assisted electrospray (ionspray) probes. In other words, many different probe designs can be used with the transmitter according to the present teachings. For example, in some electrospray probes in which a transmitter according to the present teachings is incorporated, the axial depth feature and ring shown in the above embodiment are not employed. ​

[0056] As an example, in some embodiments, an emitter according to the present teachings can be installed in an atomizer assembly using a collar and sleeve as part of an electrospray probe. For example, Figure 5 Another electrospray probe 500 is schematically depicted, in which an emitter 501 according to the present teachings is incorporated. The inlet end of the emitter 501 is installed into a low dead volume fitting (not shown) that is held in a fitting holder 505. The emitter 501 is secured in place using a sleeveless fitting 506. The emitter 501 is inserted through a probe tube 502, and the fitting holder 505 is screwed onto the probe 500 such that the outlet end of the emitter 501 protrudes through a probe outlet hole 507. The probe tube 502 is press fit into a PEEK holder 503. Nebulizer gas is provided through a channel in the PEEK holder 503 and flows down the probe tube 502, where it is released around the emitter 501 at the probe outlet hole 507. An ESI potential is applied to the outside of the conductive probe tube 502, and the inside of the probe tube 502 can include additional structures (not shown) such as internal ramps or dimples to make electrical contact with a conductive coating on the emitter 501. A mounting cap 504 is used to secure the probe 500 to an ion source.

[0057] Electrospray probes according to the present teachings can be used in a variety of different mass spectrometers. As an example, Figure 6 An example of such a mass spectrometer system 101 is schematically depicted, which includes a sample source 125 that provides a fluid sample to be ionized, an ion source 140, and a mass analyzer 160 for downstream processing of sample ions. For example, the sample source 125 can include and / or be connected to a liquid chromatography column 127. In this embodiment, the ion source includes an electrospray probe 100 according to the present teachings, such as the electrospray probes discussed above, which can provide atmospheric pressure ionization of one or more analytes in the sample.

[0058] In general, the mass spectrometer system 101 can be fluidically coupled to and configured to receive liquid samples from a variety of liquid sample sources. As non-limiting examples, the sample source 125 can include a reservoir (not shown) or an input port (not shown) through which a sample to be analyzed can be injected (e.g., manually or via an autosampler), infused, or input via a chemical electrophoresis capillary. Alternatively or additionally, and also as non-limiting examples, the sample source 125 can be connected to and / or include an LC column (e.g., of a high performance liquid chromatography (HPLC) system), such that the liquid sample to be analyzed can be in the form of an LC eluent. The sample source can also include an LC pump without a column for flow injection analysis (FIA), or a simple infusion pump to provide a liquid sample for analysis.

[0059] The LC column 127 is fluidically coupled to the ion source 140 and is configured such that one or more LC pumps (not shown) can deliver eluent from an output end of the LC column 127 to a fluidic connection 127a, through the electrospray probe 100, to an input end / proximal end 110p of the ionization discharge segment 110. The electrospray probe 100 can provide a passageway (not shown) through which fluid can be transported from the fluidic connection 127a fluidically connected to the output end of the LC column 127, through the liquid conduit 120 of the emitter 100 and the ionization discharge 110 segment to the discharge end 110d of the ionization discharge segment 110.

[0060] In some embodiments, the metal coating can include one or more layers of different metals to enhance the bonding properties to the substrate (i.e., titanium for fused silica), while the outer layer can be selected according to its chemical and physical properties. Metals such as platinum, iridium, and tungsten, and combinations thereof (alloys) can help reduce corrosion of the emitter tip during discharges. Metals such as gold and platinum can also provide excellent chemical inertness. Additionally, in some aspects, the ionization discharge end can be pre-treated in order to improve the coating of the conductive material (e.g., ion bombardment by at least one of argon, oxygen, or neon ions to form a pre-treated surface). In various aspects, a conductive coating can also be selectively applied to enhance the formation of electric fields specific to ion generation applications, and / or the discharge end can be shaped to control the electric field.

[0061] As shown, the mass spectrometer 101 can additionally include a power source 150. The power source 150 can be configured to provide power to circuitry 151 including the ionization discharge end 110d of the electrospray emitter 100. When a liquid sample is released (e.g., ejected) into the ionization chamber 112, the electrical power can ionize molecules (e.g., analytes of interest) within the liquid sample. Additionally, the mass spectrometer system 101 can include one or more ion emission current control mechanisms (not shown) to prevent the initiation of undesired discharges between the ionization discharge end 110d and the curtain plate 114a.

[0062] The mass spectrometer system 101 can also include a gas source 170 that is channeled through a gas conduit 172 to provide a means for pneumatic assistance of the electrospray or ejection.

[0063] As noted above, in some embodiments, the stationary phase of the LC column (e.g., ion exchange resin, C18, or any other suitable stationary phase) can be disposed in a portion of the emitter upstream of its conductively coated tip. As an example, Figure 7An emitter 400 is schematically shown, which comprises a sleeve 401 having an inlet port 401a for receiving a liquid sample containing or suspected of containing at least one analyte of interest, and an outlet port 401b through which charged droplets comprising ions of the analyte of interest, if present in the sample, are discharged. A column stationary phase can fill a portion or the entire sleeve 401. An ion exchange resin layer 402 is disposed in the sleeve 401 upstream of the outlet aperture thereof. Similar to the previous embodiments, the emitter 400 comprises a conductive coating 404 at its tip, which covers a portion of the outer surface and a portion of the inner surface of the emitter tip. Furthermore, similar to the previous embodiments, the tip of the emitter has a rounded profile, which can help to suppress corona discharge due to high voltage applied to the conductive coating.

[0064] The following examples are provided to further illustrate various aspects of the present teachings and are not provided to limit the best mode(s) contemplated nor the best results that can be obtained by practicing the present teachings.

[0065] Example

[0066] Figure 8 Digital photographs of the tips of the emitters are shown, which were obtained using ESI (electrospray ionization) using a 5500 QTRAP mass spectrometer sold by Sciex Corporation of Framingham, Massachusetts, USA, operated in negative ion mode while spraying a sample comprising taurocholic acid (90% water with 0.1% formic acid) with different electrospray probes having tips of different geometries.

[0067] Digital photographs of 5 emitters (3 prior art emitters with sharp tips, and 2 emitters with rounded tips according to the present teachings) are shown, which were coated with metal only on a portion of their outer surface (i.e. not internally coated), and to which different ESI potentials were applied.

[0068] The photographs show that when corona discharge conditions are severe, a bright spot or corona will be visible at the tip of the ESI emitter. For the standard grounded emitters (3 columns on the left), it is apparent that severe corona discharge has an ESI potential as low as -2000 V, while in the case of the rounded emitters (2 columns on the right), a higher ESI potential can be applied before severe corona discharge initiates, resulting in improved performance.

[0069] Figure 9Data obtained for deprotonated taurocholic acid as a function of applied ESI potential using five different ESI emitters is shown. The potential was ramped from 0 V to about -3000 V. In all cases, the signal improved when the ESI potential was set more negative than -1000 V. However, the signal dropped sharply when the corona discharge conditions became severe. An average signal gain of 1.5X order was measured using the circular emitter due to the additional 500 V that could be applied using the circular emitter. Without being bound by any particular theory, it is believed that the circular tip exhibits better corona discharge behavior (i.e., the formation of corona discharge at operating voltages is substantially suppressed) and thus improves the observed ion signal strength.

[0070] Figure 10 Results of simulations using Lorentz software to model the electric field strength at the emitter tip are shown to provide additional understanding of the difference in corona discharge inception for the grounded emitter and the circular emitter as discussed above. Figure 9

[0071] More specifically, Figure 10 Simulation results for four emitter geometries are shown. The top trace (i.e., trace A) corresponds to a prior art coated grounded emitter having a general shape similar to the shape of the emitter shown in Figure 3A The simulation shows that applying an ESI potential to this emitter geometry results in a local field hot spot with an electric field of the order of 1.2E8 V / m.

[0072] Traces C and D show the electric field simulation results for the circular emitter according to the emitters shown in Figure 3B and 3C As discussed above. Trace C shows that the circularization of the outer surface of the emitter significantly reduces the maximum electric field by about 4X. The lower electric field means that a higher ESI potential can be applied before severe corona discharge inception, which in turn results in an improvement in the signal to noise ratio (SNR) as shown in Figure 9 The maximum electric field hot spot occurs on the surface where the coated front surface of the emitter meets the uncoated interior channel. Extending the conductive coating into the interior channel can eliminate the field hot spot shown in the bottom trace (i.e., trace D) (where the entire outer circular surface and interior channel are held at the same potential). In particular, the simulation shows that the average electric field over the entire emitter tip can be reduced by another 3-4X by extending the coating into the interior of the emitter tip.

[0073] Those of ordinary skill in the art will appreciate that various changes can be made to the embodiments described above without departing from the scope of the present application.​

Claims

1. An electrospray emitter for use in an electrospray ion source, comprising: a sleeve extending from a proximal end having an inlet orifice for receiving a liquid sample containing at least one analyte to a discharge emitter end having an outlet orifice through which charged droplets of ions containing the analyte are discharged, and an electrically conductive coating covering at least a portion of an outer surface and at least a portion of an inner surface of the emitter end, wherein the at least a portion of an outer surface of the emitter end and the coating covering the outer surface of the emitter end comprises a rounded conical tip extending to the outlet orifice of the emitter end.

2. The electrospray emitter of claim 1, wherein, the rounded conical tip has a radius of curvature in a range of 20 microns to 200 microns.

3. The electrospray emitter of claim 1, wherein, the proximal end of the sleeve is configured to be coupled to a liquid chromatography (LC) column to receive the liquid sample.

4. The electrospray emitter of claim 1, further comprising a stationary phase of an LC column disposed in a portion of the sleeve upstream of the outlet orifice.

5. The electrospray emitter of claim 1, wherein, the electrically conductive coating comprises any one of a single layer and a multi-layer coating of a metal or an alloy.

6. The electrospray emitter of claim 1, wherein, the electrically conductive coating has a thickness in a range of 5 Angstroms to 5 microns.

7. The electrospray emitter of claim 1, wherein the sleeve is configured to accommodate a flow rate of the liquid sample in a range of 1 nL / min to 5 mL / min.

8. The electrospray emitter of claim 7, wherein the outlet orifice has a diameter in a range of 1 micron to 150 microns.

9. The electrospray emitter of claim 1, wherein the outlet orifice of the sleeve has a diameter in a range of 2 microns to 40 microns and is configured for nano-flow electrospray ionization at a flow rate of less than 2 microliters / minute.

10. A mass spectrometer system, comprising: an ion source having an electrospray probe for generating ions, a curtain plate having an orifice for receiving at least a portion of the ions, one or more mass analyzers disposed downstream of the orifice of the curtain plate, wherein the electrospray probe comprises: a sleeve extending from a proximal end having an inlet orifice for receiving a liquid sample containing at least one analyte to a discharge emitter end having an outlet orifice through which charged droplets of ions containing the analyte are discharged, and an electrically conductive coating covering at least a portion of an outer surface and at least a portion of an inner surface of the emitter end, wherein the at least a portion of an outer surface of the emitter end and the coating covering the outer surface of the emitter end comprises a rounded conical tip extending to the outlet orifice of the emitter end.

11. The mass spectrometer system of claim 10, wherein the rounded conical tip has a radius of curvature in a range of 20 microns to 200 microns.

12. The mass spectrometer system of claim 10, wherein, the proximal end of the sleeve is configured to be coupled to a liquid chromatography (LC) column to receive the liquid sample.

13. The mass spectrometer system of claim 10, further comprising a stationary phase of an LC column disposed in a portion of the sleeve upstream of the outlet orifice.

14. The mass spectrometer system of claim 10, wherein, the electrically conductive coating comprises any one of a single layer and a multi-layer coating of a metal or an alloy.

15. The mass spectrometer system of claim 10, wherein, The electrically conductive coating has a thickness in the range of 50 Angstroms to 5 microns.

16. The mass spectrometer system of claim 10, wherein, The sleeve is configured to accommodate a flow rate of the liquid sample in the range of 1 nL / min to 5 mL / min.

17. The mass spectrometer system of claim 16, wherein, The outlet orifice has a diameter in the range of 1 micron to 150 microns.

18. The mass spectrometer system of claim 10, wherein, At least one of the mass analyzers comprises a quadrupole mass analyzer.

19. The mass spectrometer system of claim 10, further comprising a detector arranged downstream of the one or more mass analyzers for detecting ions and producing an ion detection signal.

20. The mass spectrometer system of claim 19, further comprising an analyzer for receiving the ion detection signal and producing a mass spectrum of the ions.

21. A method for ionizing a sample, comprising: providing an electrospray probe comprising a sleeve extending from a proximal end having an inlet orifice for receiving a liquid sample containing at least one analyte to a discharge emitter end having an outlet orifice through which charged droplets of ions containing the analyte are discharged, and an electrically conductive coating covering at least a portion of an outer surface and at least a portion of an inner surface of the emitter end, wherein the at least a portion of the outer surface of the emitter end and the coating covering the outer surface of the emitter end comprise a rounded conical tip extending to the outlet orifice of the emitter end, maintaining the electrically conductive coating at a potential difference relative to a counter electrode, introducing a liquid sample into the sleeve via the inlet orifice so as to provide a flow of the liquid sample from the inlet orifice to the outlet orifice, wherein the liquid sample is discharged as a plurality of charged droplets of ions containing the analyte via the outlet orifice.

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