Integrated electro- spray emitter and method of manufacturing the same

Abstract

The present disclosure relates to integrated electrospray emitters and methods of manufacturing the same. An electrospray ionization emitter according to various aspects described herein can include an emitter body formed using fused silica. The emitter body can include a fluid conduit segment including a liquid connection end that has been coated with polyether ether ketone (PEEK) over at least a portion of the liquid connection end. The liquid connection end can have a first outer diameter configured to connect to a sample source to receive a sample liquid for ionization from the sample source. The emitter body can also include an ionization discharge segment fluidically connected to the fluid conduit segment. The ionization discharge segment can have an ionization discharge end coated with a conductive material over at least a portion of the ionization discharge end and configured to have a second outer diameter that allows for ionization of the liquid sample.

Description

[0001] This application is a divisional application of the application for patent having application number 201980016417.8, filed on March 1, 2019, entitled “Integrated Electrospray Emitter and Methods for Making Same”.

[0002] Related Applications

[0003] This application claims priority to U.S. Provisional Application No. 62 / 636,909, filed March 1, 2018, entitled “Integrated Electrospray Emitter and Methods for Making Same”, and U.S. Provisional Application No. 62 / 811,759, filed February 28, 2019, entitled “Integrated Electrospray Emitter and Methods for Making Same”, both of which are incorporated by reference herein in their entirety. TECHNICAL FIELD

[0004] The present invention relates generally to electrospray emitters, and more particularly, to integrated electrospray emitters having an ionizing discharge end and a fluidic connection end. BACKGROUND

[0005] Mass spectrometry (MS) is an analytical technique used to measure the mass-to-charge ratio of molecules within a sample, both qualitatively and quantitatively. MS can be useful for identifying unknown compounds, determining the isotopic composition of elements in a molecule, determining the structure of a particular compound by observing fragmentation of the compound, and quantifying 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 during the sampling process. Due to the precision and sensitivity requirements of most MS applications, complex samples are often subjected to a separation technique prior to ionization.

[0006] Over the years, various sampling techniques have been developed to convert chemical entities within a liquid sample into charged ions suitable for detection with MS. One of the more common methods of ionization is electrospray ionization (ESI) (e.g., pneumatically assisted electrospray, nanoelectrospray), due to its ability to perform functions such as transferring molecules including large macromolecules from solution to the gas phase as intact multi-charge molecular ions, and its ease of coupling to a variety of sample sources including liquid chromatography and capillary electrophoresis.

[0007] A typical electrospray emission process can occur when electrostatic forces overcome surface tension at the surface of a liquid sample. Specifically, in a typical ESI process, a liquid sample is discharged into an ionization chamber via an electrically conductive needle, electrospray electrode, or nozzle while a potential difference between the electrospray electrode and a counter electrode generates 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 drawn 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.

[0008] Accordingly, electrospray processes often require a high electric field to be generated at the emitter tip of the electrospray electrode. This requirement, along with surface tension considerations within the Taylor cone, often calls for an electrospray electrode emitter tip having a small inner diameter (ID). In conventional ESI, the electrospray electrode traditionally includes a metal capillary (e.g., stainless steel) from which the liquid sample is discharged into the ionization chamber and to which a voltage of several kilovolts is applied relative to the counter electrode. As ESI-based techniques increasingly emphasize ionization efficiency and / or reduced sample consumption (e.g., by reducing the size of the sample needle to reduce the volumetric flow rate of the liquid sample), manufacturing constraints regarding the size of the metal capillary have led to the use of metallized silica capillaries. For example, silica capillaries can be produced having a relatively small inner diameter (ID), which can then be coated with a thin layer of an electrically conductive material (e.g., gold). As a non-limiting example, while it is generally difficult to produce stainless steel capillaries having an ID of less than about 70 pm, metallized silica capillaries can exhibit an ID as low as 5 pm.

[0009] Additionally, the inlet end of an electrospray electrode also needs to be physically connected to a source (e.g., a reservoir) containing the liquid sample being electrosprayed. This liquid connection often needs to be of an outer diameter (OD) that is larger (e.g., 2 to 10 times) than the outer diameter of the emitter tip. This difference between the liquid connection and the outer diameter of the emitter is often dealt with in the art by using a reducer fitting or a sleeve and fitting. However, the addition of a sleeve and fitting can complicate the process of implementing and / or connecting various parts of the electrode. For example, to properly utilize the fitting, a user would have to adjust the position of the fitting until a specific length (e.g., 0.5 mm to 1 mm) of the emitter tip protrudes from the sprayer head. Additionally, in some cases, the fitting can be connected such that it provides electrical isolation of the emitter tip from a liquid chromatography (LC) connection that is manipulated by the user. This need can further complicate the implementation and connection of an electrospray emitter. SUMMARY

[0010] Described herein are integrated, monolithic (permanently attached), easy-to-use electrospray emitters having an ionization discharge end and a fluid connection end. In some aspects, the integrated electrospray emitter can have an ionization discharge end comprising a material such as fused quartz and a fluid connection end comprising fused quartz coated by a material such as polyether ether ketone (PEEK).

[0011] In an aspect, an electrospray ionization emitter is disclosed. The electrospray ionization emitter can include an emitter body comprising fused quartz. The emitter body can include a fluid or liquid conduit segment having a liquid connection end. The liquid connection end can be coated with polyether ether ketone (PEEK) over at least a portion of the liquid connection end, and the liquid connection end can have a first outer diameter configured for connection to and receiving a sample liquid for ionization from a sample source (e.g., a liquid chromatography (LC) column). In another aspect, the liquid conduit segment can be made of PEEK only. The emitter body can also include an ionization discharge segment fluidically connected to the fluid conduit segment. The ionization discharge segment can have an ionization discharge end. At least a portion of the ionization discharge end can be coated with an electrically conductive material over at least a portion thereof and can exhibit a second outer diameter configured to allow ionization of the liquid sample. The second outer diameter can be smaller than the first outer diameter.

[0012] According to various aspects of the present teachings, a method for manufacturing an electro-spray ionization emitter is provided. The manufacturing method can include connecting a fluidic conduit segment having a liquid connection end to an ionization discharge segment having an ionization discharge end to form an emitter body. The emitter body can include fused quartz. The manufacturing method can further include coating the liquid connection end with a polyether ether ketone (PEEK) over at least a portion of the liquid connection end to form a first outer diameter at the liquid connection end that allows the liquid connection end to be connected to a sample source (e.g., an LC column) to receive a sample liquid for ionization from the sample source. The manufacturing method can further include coating at least a portion of the ionization discharge end of the ionization discharge segment with a conductive material such that the ionization discharge end includes a second outer diameter configured to allow ionization of the liquid sample. As a non-limiting example, the conductive coating can be a metal applied via a solution (e.g., an electroplating process), by chemical vapor deposition (e.g., evaporation deposition), and / or physical deposition (e.g., coating, sputter coating). In some aspects, 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 quartz), while an outer layer can be selected for its chemical and physical properties. Metals such as platinum, iridium, and tungsten, and combinations thereof (alloys) can help reduce electrical discharge erosion. Metals such as gold and platinum can also provide superior chemical inertness.

[0013] In other examples, any of the above aspects or any system, method, device described herein can include one or more of the following features.

[0014] In various aspects, at least a portion of the fluidic conduit segment can include an enhancement coating. The enhancement coating can be configured to facilitate the coating of at least a portion of the fluidic conduit segment with the PEEK. In some example aspects, the enhancement coating can include a polyimide.

[0015] In certain aspects, the ionization discharge end can be configured to allow for electrostatic field effects. As a non-limiting example, the ionization discharge end can be shaped to control the electric field. Additionally or alternatively, the conductive coating can be selectively applied to enhance the formation of the electric field specific to ion generation applications. The ionization discharge end can include a pre-treatment surface. The pre-treatment surface can be configured to improve the coating of the ionization discharge end with the conductive material. Additionally, the ionization discharge end can be subjected to ion bombardment by at least one of argon, oxygen, or neon ions to form the pre-treatment surface.

[0016] Additionally or alternatively, the emitter body can include at least one permanently deformable and / or non-deformable mechanical connection that connects the fluid conduit segment with the ionization discharge segment. The mechanical connection can be established using at least one of a clamp, ferrule, crimp, or any other suitable device. Additionally, in some aspects, the mechanical connection can be configured such that it is movable about the fluid conduit segment and the ionization discharge segment to allow for positioning adjustment of the emitter body prior to electrode assembly.

[0017] Additionally, the emitter body can include insulating material on at least a portion of the fluid conduit segment to allow a user to manipulate the emitter. In various embodiments, the insulating material can be an electrically insulating material. A positioning ring can be included in the emitter body to indicate to a user the insulated portion of the fluid conduit segment and / or to help ensure accurate placement within the ion source housing. If the emitter is part of a charge-aided electrospray, the positioning ring can ensure proper and accurate positioning of the ionization discharge end relative to the nebulizing gas nozzle. The positioning ring can also provide a means for sealing the nebulizing gas within the gas channel. In various aspects, a deformable O-ring can provide the nebulizing gas seal for charge-aided electrospray operation.

[0018] Other aspects and advantages of the present application can become apparent from the following drawings and description, all of which are intended to illustrate the principles of the application. BRIEF DESCRIPTION OF DRAWINGS

[0019] The features and advantages described herein can be better understood with reference to the following description together with the accompanying drawings. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the application. Those skilled in the art will appreciate that the following description is merely exemplary in nature. The drawings are not intended to limit the scope of the application in any way.

[0020] Figure 1 is a schematic illustration of an electrospray emitter in accordance with various aspects of the Applicant's teachings.

[0021] Figure 2A is an example illustration of a one-piece electrospray emitter in accordance with various aspects of the Applicant's teachings.

[0022] Figure 2B is an example illustration of a multi-piece electrospray emitter in accordance with various aspects of the Applicant's teachings.

[0023] Figure 3 is a cross-sectional schematic illustration of a probe that can be used for one-piece electrode electrospray ionization (ESI) in accordance with various aspects of the Applicant's teachings.

[0024] Figure 4is a cross-sectional schematic illustration of a probe that can be used for multi-piece electrode electrospray ionization (ESI) according to various aspects of the Applicant's teachings.

[0025] Figure 5 is a cross-sectional detail of a schematic illustration of a probe that can be used for multi-piece electrode electrospray ionization (ESI) according to various aspects of the Applicant's teachings.

[0026] Figure 6 is a cross-sectional detail of a schematic illustration of a probe that can be used for multi-piece electrode electrospray ionization (ESI) according to various aspects of the Applicant's teachings. DETAILED DESCRIPTION

[0027] The present disclosure relates to integrated easy-to-use electrospray emitters having an ionization discharge end and a fluid connection end. In various aspects, the integrated electrospray emitters can have an ionization discharge end comprising a material such as fused silica and a fluid connection end comprising a liquid conduit comprising fused silica coated with a material such as polyether ether ketone (PEEK).

[0028] In various aspects, the electrospray emitters according to the present teachings can allow for direct coupling of a chromatographic column, thereby eliminating intermediate tubing and connectors that can be difficult and / or cumbersome to connect to known electrospray emitters. Additionally or alternatively, direct coupling can address issues with chromatographic dead volumes that can occur over a flow rate dynamic range of 10,000 or more (i.e., from about 100 nL / min to about 2 mL / min). Additionally, the electrospray emitters according to various aspects disclosed herein can allow for a complete novice to chromatography or liquid chromatography to more easily connect a column to an emitter with a high success rate (e.g., 100% success rate) without requiring the person to have any substantial training or guidance in connecting the emitter.

[0029] In various aspects, the emitters according to the present teachings can include an integrated one-piece (monolithic) electrode. The emitters can include an ionization discharge segment and a fluid conduit segment. For example, the ionization discharge segment can include fused silica and the fluid connection segment can have a fluid connection end comprising fused silica that has been coated with a PEEK polymer outer layer at least a portion of the fused silica. The fused silica ionization discharge segment can be configured such that it is in direct contact with the conduit segment.

[0030] Electrospray ionization (ESI) mass spectrometry (MS) emitters according to various aspects described herein can provide superior performance over currently available fused silica emitters. Specifically, by integrating fused silica with PEEK polymer, integrated emitters according to various aspects of the present teachings can be able to efficiently produce ions across a flow dynamic range of about four orders of magnitude (e.g., across about 10,000 nL / min) as well as enable zero peak dispersion across a flow range from about 100 nL / min to about 2 mL / min as non-limiting examples. Additionally, by combining fused silica and PEEK polymer into a single-piece emitter, integrated emitters according to various aspects described herein can be an easy-to-use option for less experienced personnel in the field of mass spectrometry, for example, by reducing the steps (and their difficulty) required to fluidically couple an emitter to a sample source (e.g., an LC column). In contrast, currently available silica ESI emitters can neither provide similar performance (e.g., over similar flow ranges) nor can they be easily used by novices in the field of mass spectrometry. Additionally, integrated electrodes according to the present teachings can provide additional flexibility by allowing for maximized ionization at any flow rate (assuming the use of appropriate electrodes) as well as better performance (e.g., by reducing or eliminating band broadening).

[0031] ESI emitters according to various aspects of the present teachings can provide an integrated ESI electrode that combines a practical liquid connection at its inlet with a high performance emitter tip to form a single monolithic (i.e., indivisible) device. In some aspects, an ESI emitter can include a fused silica conduit (e.g., capillary) at least partially surrounded by PEEK. For example, a fluid connection end can include a small outer diameter (OD) fused silica (e.g., coated with a thin layer of polyimide) that can be over-coated in a material such as PEEK polymer to form a practical (e.g., larger) outer diameter for receiving fluid from a sample source to be discharged into an ionization chamber. Specifically, an ESI electrode according to various exemplary aspects of the present teachings can include an emitter discharge tip that includes (e.g., consists only of) fused silica and has a surface for local electrical conductivity enhancement (e.g., via a metallized discharge end). An exemplary ESI electrode can also include fused silica coated by a material such as PEEK at its liquid connection end for enabling fluidic connection to a sample source. In various aspects, this configuration can simplify the work required to implement an emitter as it no longer requires the user to contend with the outer diameter difference of the emitter tip and liquid connection, which typically requires connecting multiple conduits and connectors to provide the proper inner diameter reduction of the liquid conduit extending from the sample source to the discharge end. Additionally, the high electrical resistance of PEEK, polyimide, and fused silica can provide the necessary electrical isolation for insulating the LC end of the ESI electrode from user manipulation.

[0032] Figure 1 is a schematic illustration of an electrospray emitter 100 according to some aspects disclosed herein. As shown, the electrospray emitter 100 can be used in a mass spectrometer system 101. The electrospray emitter 100 can include an ionization segment 110 having an ionization discharge end 110d and a liquid conduit 120 having a fluid connection end 127a. In some aspects, the ionization segment 110 can include fused silica (e.g., only fused silica), and the liquid conduit segment 120 can include fused silica coated with a layer of polymer such as PEEK. The ionization segment 110 can be in direct contact with the liquid conduit segment 120.

[0033] An example mass spectrometer system 101 can include a sample source 125 providing 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. As shown in Figure 1 The electrospray emitter 100 provides a flow path connecting the liquid chromatography column 127 to the ion source 140.

[0034] In general, the mass spectrometer system 101 can be fluidically coupled to various liquid sample sources and configured to receive a liquid sample from the sample source. As a non-limiting example, 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 capillary chemical electrophoresis. Alternatively or additionally, as also a non-limiting example, 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. In Figure 1 In the example shown in

[0035] The emitter 100 can be made of any suitable material known in the art. For example, the emitter 100 can include a permanently formed fused quartz channel. The permanently formed fused quartz emitter 100 can be a single fused quartz tube, or formed from one or more independent sections that have been integrated into a single piece emitter. In some aspects, the emitter 100 can include a material such as small OD silica that is overclad in a material such as PEEK polymer over the liquid conduit section 120. The PEEK polymer at the liquid conduit section 120 can provide the actual outer diameter typically required to form a fluidic connection 127a with the LC column 127, such that a sleeve or adapter is not required to make the connection. The emitter 100 can include a material over at least a portion of the liquid conduit section 120 that facilitates the overcladding of the liquid conduit section 120 with the PEEK polymer. For example, the fused quartz fluidic conduit can include an enhanced overclad that allows the fused quartz to be further overclad with a material such as PEEK. The enhanced overclad can include any suitable material available in the art. For example, the enhanced overclad can be polyimide.

[0036] At the ionizing discharge side 110, the emitter 100 can have an emitter discharge tip 1 lOd that is made of a material such as fused quartz and is enhanced for local electrical conductivity to charge the liquid and create an electric field. Thus, the emitter 100 can provide a fluidic connection of the LC column 127 to the ion source 140, while removing the need for the user to contend with the OD difference required to connect to the LC column 127 and the ion source 140. As a non-limiting example, the emitter discharge tip 1 lOd can include a conductive coating (e.g., metal) applied via an electroplating process, by chemical vapor deposition (e.g., evaporation deposition), and / or physical deposition (e.g., coating, sputter coating). In some aspects, 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 quartz), while the outer layer can be selected for its chemical and physical properties. Metals such as platinum, iridium, and tungsten, and combinations thereof (alloys) can help to reduce corrosion of the tip 1 lOd during discharge. Metals such as gold and platinum can also provide superior chemical inertness. Additionally, in some aspects, the ionizing discharge end can be pre-treated in order to improve the coating of the conductive material (e.g., via ion bombardment by at least one of argon, oxygen, or neon ions to form a pre-treated surface). In various aspects, the conductive coating can also be selectively applied to enhance the formation of the electric field specific to the ion generation application, and / or the discharge end can be shaped to control the electric field.

[0037] Referring back to Figure 1The ion source 140 may typically include an electro-jet ion source comprising at least a portion of the ionization emission section 110 of the electro-jet emitter 100. For example, as described above, the ionization emission section 110 may terminate at an emission tip 110d configured to eject a liquid sample into a heated ionization chamber 112 heated by a heater 180. The heated ionization chamber 112 may be in fluid communication with a sampling orifice 114b of the panel 114a and an inlet orifice 116b of the mass analyzer 160.

[0038] As shown, the mass spectrometer 101 may additionally include a power supply 150. The power supply 150 may be configured to provide power to circuitry 151 containing the ionization emission terminal 110d of the electroejector 100. This power can ionize molecules (e.g., analytes of interest) within the liquid sample when it is discharged (e.g., ejected) into the ionization chamber 112. Additionally, the mass spectrometer system 101 may include one or more ion emission current mechanisms (not shown) to prevent the initiation of unwanted discharges between the ionization emission terminal 110d and the curtain plate 114a.

[0039] The mass spectrometer system 101 may also include a gas source 170, through which gas is directed via a gas conduit 172 to provide means for gas-assisted electro-jet or jetting.

[0040] In addition, such as Figure 1 As shown, in some aspects, the emitter 100 may include a positioning ring 130. The positioning ring 130 can be used to identify the insulated portion of the emitter 100 and can help ensure accurate placement within the ion source housing and gas conduit 172 (if present). In various embodiments, the positioning ring may be part of a collar or a separate collar. Specifically, as described above, the liquid conduit segment 120 of the emitter 100 may be encased in an insulating material (e.g., a PEEK polymer). Since this segment 120 of the emitter 100 may come into direct contact with a user (e.g., the user's hand), the positioning ring 130 can be used to mark the end of the insulated segment 120 to prevent accidental contact between the user and the conductive segment of the emitter 100 (i.e., the ionization segment 110). Additionally, the length of the emitter 100 distal to the positioning ring 130 can be selected to extend an appropriate distance into the ionization chamber 112 and the gas conduit 172 (if present). In this way, when the emitter 100 is coupled to the ion source housing, the positioning ring 130 can be positioned against the shoulder of the housing to help provide accurate placement of the emitter 100 therein.

[0041] Figure 2A This is an example illustration of a one-piece electro-jet launcher 200 based on various aspects of this teaching. (See illustration for example.) Figure 2AAs shown, the one-piece electro-jet emitter 200 may comprise a continuous piece of any suitable material, such as a fused silica tube. An insulating polymer, such as PEEK, may be molded or extruded onto the fluid 220 of the emitter 200. Molding or extruding PEEK onto fused silica can form a shape for attachment to an LC column (e.g., Figure 1 The liquid connection end of the LC column 127 in the LC column. The fused silica fitting can provide the ID necessary for electro-jetting of the sample on the ionization side 210. An insulating polymer molded or extruded onto the fused silica can also provide the OD required for connection to the LC column and receiving the fluid sample on the liquid conduit segment 220. For example, in one embodiment, the liquid conduit segment may include a portion having approximately [missing information - likely a diameter or diameter] for connection to the LC column. or Pipe with an outer diameter (OD) of inches.

[0042] Additionally, as referenced Figure 1 As noted, the positioning ring 230 can be used to identify the insulated portion of the transmitter 200 and ensure proper placement of the transmitter 200 with the ion source housing. Specifically, since the insulated liquid conduit segment 220 of the transmitter 200 can come into direct contact with the user (e.g., the user's hand), the positioning ring 230 can be used to mark the end of the insulated segment 220 to prevent the user from accidentally coming into contact with the conductive portion of the transmitter 200 (i.e., the ionization tip 210d). In various embodiments, the transmitter 200 may include a ring cap 240.

[0043] Despite Figures 1 to 2A The present invention is shown as a single-piece electro-jet launcher, but the launcher according to the various aspects provided herein may include two or more pieces that have been connected to form an integrated electro-jet launcher. Figure 2B This is an example illustration of a multi-piece electro-jet launcher 200' according to some embodiments disclosed herein. Figure 2B In the example shown, transmitter 200' includes two parts 210' and 220' that have been connected to form an integrated (monolithic) transmitter 200'. Specifically, as Figure 2B As shown, emitter 200' may include an ionization emission section 210' and a liquid conduit section 220'. Ionization emission section 210' may include any suitable material available in the art. For example, ionization emission section 210' may be an ejector tube comprising materials such as fused silica or stainless steel. Liquid conduit section 220' may also include any suitable material known in the art. For example, liquid conduit section 220' may include an internal portion formed of a material such as fused silica that has been coated with one or more sheets of a polymer (e.g., PEEK polymer), and / or formed of other suitable materials such as PEEK.

[0044] The liquid conduit segment 220' and the ionization discharge segment 210' can be connected to form an integrated (monolithic) electrospray emitter 200'. Generally, any suitable means available in the art can be used to connect the liquid conduit segment 220' and the ionization discharge segment 210'. For example, as shown in FIG. 3A, any of a ferrule, ring, or cap 299' can be used to connect the liquid conduit segment 220' to the ionization discharge segment 210'. As noted with reference to FIG. 2A, the liquid conduit segment 220' can include an electrically insulating layer that allows a user to directly interact with and / or manipulate the emitter 200'. A positioning ring 230' can be used to identify this insulated portion 220' of the emitter 200' to prevent a user from accidentally contacting the electrically conductive portion of the emitter 200' (i.e., the discharge end 210'd). In some aspects, the length of the emitter 200' distal of the positioning ring 230' can be selected to extend a suitable distance into the ionization chamber 112 (as shown in FIG. 1A). Figure 2B Figure 2A Figure 1

[0045] Figure 3 is a cross-sectional schematic illustration of a probe 301 that can be used for electrospray ionization (ESI) according to some embodiments disclosed herein. The probe 301 can be any suitable probe used in the relevant art for performing ionization of a sample. For example, the probe 301 can be an electrospray ionization (ESI) probe.

[0046] The probe 301 can include a probe body 398 having a channel 397 extending therethrough through which the emitter 300 can be installed. As noted above, the one-piece electrode emitter 300 also provides a channel (e.g., microchannel) that extends from the inlet end 327a (fluid connection end) to the ionization discharge end 310d and out of the probe body 398 of the probe 301. The emitter 300 includes a liquid conduit segment 320 and an ionization segment 310 formed using any suitable material such as a fused silica tubing or stainless steel. An insulating polymer such as a PEEK polymer can be molded or extruded onto the liquid conduit segment 320 of the emitter 300. As noted above, the molding or extrusion of the polymer onto the fused silica can be used to form a liquid connection to an LC column. The emitter 300 contains an axial depth positioning feature, i.e., a positioning ring 330, that enables a user to accurately and simply install the emitter tip. As noted above, the positioning ring 330 can be used to identify the location of the emitter tip 310d within the ionization chamber 112 (as shown in FIG. 1A). Figure 3 ​​​As shown in FIG. 3, the positioning nut 350 can be used to secure the positioning ring 330 in place, aligning the emitter on the positioning collar seat 360 without any further adjustment by the user. The emitter 200 can include a ring cap 340. An O-ring 380 seals the positioning ring 330 within the collar seat 360, preventing any auxiliary gas from flowing back into the emitter probe body.

[0047] Fused quartz covered with molded or extruded PEEK can provide the actual OD on the liquid conduit segment 320 for connecting to the LC column and receiving the fluid sample. For example, in an aspect, the liquid conduit segment can provide a tube having an outer diameter (OD) of about 150 μιη or in a range from about 150 μιη to about 1.6 mm for connecting to the LC column at the inlet end 327a of the emitter 300. or 1.6 mm. The fused quartz or stainless steel tubing can also provide the ID necessary at the ionization discharge side 310d to enable electrospray of the sample. The ID at the ionization discharge end 310d can be, for example, from about 10 μιη to about 500 μιη.

[0048] The emitter can be a one-piece electrode Figure 3 ) or a multi-piece electrode Figure 4 ). The probe 401 can include a probe body 498 having a channel 497 extending therethrough through which the emitter 400 can be installed. The electrospray emitter 400 includes a liquid conduit segment 420 and an ionization segment 410 formed using any suitable material such as fused quartz tubing or stainless steel. An insulating polymer such as a PEEK polymer can be molded or extruded onto the liquid conduit segment 420 of the emitter 400. As described above, the molding or extrusion of the polymer onto the fused quartz can be used to form the liquid connection to the LC column. The emitter 400 contains axial depth positioning features, namely two-piece collars 430 and 499. The two-piece collars perform two functions - the first is to enable the user to accurately install the emitter tip and the second function is to act as a joint for the liquid conduit segment 420 and the ionization segment 410 of the emitter. With the positioning nut 450 as shown in FIG. 4, the two-piece collars 430 and 499 are secured in place, aligning the emitter on the positioning collar seat 460 without any further adjustment by the user. Figure 4

[0049] Fused quartz covered with molded or extruded PEEK can provide the actual OD on the liquid conduit segment 420 for connecting to the LC column and receiving the fluid sample. For example, in an aspect, the liquid conduit segment can provide a tube having an outer diameter (OD) of about 150 μιη or in a range from about 150 μιη to about 1.6 mm for connecting to the LC column at the inlet end 427a of the emitter 400. or ​tubes of an inner diameter (ID) of from about 10 pm to about 500 pm or an outer diameter (OD) of from about 150 pm to about 1.6 mm. The fused silica or stainless steel tubing can also provide the ID necessary to achieve e-jetting of the sample at the ionization discharge side 410d. The ID at the ionization discharge end 410d can be, for example, from about 10 pm to about 500 pm.

[0050] Figure 5 is a cross-sectional schematic illustration of another integrated monolithic multi-piece ESI probe 501 according to some embodiments disclosed herein. As Figure 5 shown in FIG. 6B, the probe 501 can include an ionization discharge segment 510 and a fluid conduit segment 520 as otherwise discussed herein. The ionization discharge segment 510 and the fluid conduit segment 520 can be fluidically connected to form a channel that fluidically connects an LC column at a fluid connection end 527 of the emitter 500 to an ionization discharge end 510d of the emitter 500.

[0051] As discussed above, the fluid conduit segment 520 and the ionization discharge segment 510 of the emitter 500 can be mechanically connected using any suitable means known in the art. For example, clamping or locking rings 530, 530' can be used to mechanically connect and lock the two segments 510, 520 to each other within a ferrule or joint 580. Additionally, as Figure 5 shown in FIG. 6B, the emitter 500 can be configured to ensure accurate placement within the ion source housing and within the nebulization assist gas nozzle (if present). For example, the length of the emitter distal of the clamping ring 530 can be selected such that the emitter 500 extends into the ionization chamber a proper distance. Additionally, the locking rings 530, 530' can be configured such that they can lock the emitter ionization discharge segment 510 and the fluid conduit 520 relative to each other within the ferrule 580 to prevent undesired movement of the emitter ionization discharge segment 510 and the fluid conduit 520 relative to each other.

[0052] As discussed above, the e-jet emitter according to various aspects described herein can include two or more pieces that have been connected to form an integrated monolithic e-jet emitter. Figure 6 is a cross-sectional schematic illustration of a multi-piece electrode. An ESI emitter 600 according to some aspects disclosed herein. As Figure 6 shown in FIG. 6B, the emitter 600 includes two pieces 610, 620 that have been connected to form an integrated monolithic emitter 600. As otherwise discussed herein, the first segment 610 of the emitter 600 can be an ionization discharge segment and the other portion 620 of the emitter 600 can be a liquid conduit 620. The ionization segment 610 can include any suitable material available in the art. For example, the ionization segment 610 can be an e-jet emitter tube including a material such as fused silica or stainless steel.

[0053] The liquid conduit segment 620 may also comprise any suitable material known in the art. For example, the liquid conduit segment 620 may comprise one or more pieces of material such as fused silica coated with other materials such as PEEK.

[0054] The liquid conduit section 620 and the ionization emission section 610 can be connected to form an integrated electro-jet emitter 600. Specifically, once connected, the liquid conduit section 620 and the ionization emission section 610 form a structure for generating an electro-jet emitter from an LC column (e.g., Figure 1 The channel of the flow path from the LC column 127 to the emission end of the transmitter.

[0055] Typically, any suitable device available in the art can be used to connect the liquid conduit section 620 and the ionization discharge section 610. For example, such as Figure 6 As shown, the liquid conduit segment 620 and the ionization discharge segment 610 can be fluidly connected via a fluid passage 695. The fluid passage 695 can be formed of any suitable material available in the art. For example, the fluid passage 695 can be made of a deformable or non-deformable material (e.g., stainless steel). Additionally, as described above, the liquid conduit segment 620 and the ionization discharge segment 610 can also be mechanically connected to each other via two-piece ferrule connectors 630 and 699, 699'. Any suitable means available in the art can be used to establish the mechanical connection. As a non-limiting example, in some aspects, a polychlorotrifluoroethylene (commonly referred to as Kel-F) ferrule can be used to establish the mechanical connection 630 and 699, 699'. Additionally or alternatively, in some embodiments, a non-deformable material such as stainless steel or a deformable material such as PEEK can be used to establish the connection 630 and 699, 699'. The deformable connection can be secured using two-piece positioning compression rings 699 and 699' compression collars 630 surrounding the fluid conduit 620 and the ionization discharge section 610. Additionally, as... Figure 6 As shown, the emitter 600 can be configured to ensure accurate placement within the ion source housing and the atomizing auxiliary gas nozzle (if present). The length of the emitter at the distal ends of the two-piece collars 630 and 699, 699' can be selected to allow the emitter 600 to extend an appropriate distance into the ionization chamber. Additionally, the positioning rings 630, 699, 699' can be configured to position the emitter ionization emission section 610 within the ESI probe to prevent undesirable movement of the emitter ionization emission section 610.

[0056] It should be understood that the above discussion will illustrate aspects of the embodiments of the Applicant's teachings in connection with which some specific details can be omitted in order to avoid unnecessarily obscuring the present description. For example, discussion of well-known ideas or concepts can be slightly simplified. For the sake of brevity, well-known ideas or concepts will not be discussed in any detail. Skilled persons will recognize that some embodiments of the Applicant's teachings can not require certain specific described details in every implementation, and the description herein is merely provided to give a thorough understanding of the embodiments. Similarly, it will be apparent to the skilled person that the described embodiments can be readily adapted or varied, according to well-known principles, without departing from the scope of the present disclosure. The above detailed description of the embodiments will not be considered to be limiting in any way. As used herein, the terms "about" and "substantially equal" refer to variations in numerical quantity that can occur, for example, through measurement or manipulation processes in the real world, through inadvertent error in these processes, through differences in manufacture, source, or purity of compositions or reagents, and the like. Generally, the terms "about" and "substantially equal" as used herein mean plus or minus 1 / 10 of the indicated value or range of values, e.g., ±10%. For example, a concentration value of about 30% or substantially equal to 30% can mean a concentration between 27% and 33%. These terms also refer to variations that will be recognized by the skilled person to be equivalent, provided that these variations do not encompass values that are known to be practiced by the prior art.

[0057] Those of ordinary skill in the art will appreciate that various changes can be made to the above-described embodiments without departing from the scope of the present disclosure. All such modifications or variations are considered to be within the scope of the Applicant's teachings as defined by the following claims.

Claims

1. An electrospray ionization emitter, comprising: an emitter body comprising fused quartz, the emitter body comprising: a fluid conduit segment having a liquid connection end coated with polyether ether ketone (PEEK) on at least a portion of the liquid connection end and having a first outer diameter configured for connection to and receiving a sample liquid for ionization from a sample source; an ionization discharge segment fluidically connected to but not in contact with the fluid conduit segment, the ionization discharge segment not coated with PEEK thereon, the ionization discharge segment having an ionization discharge end coated with a conductive material on at least a portion of the ionization discharge end and having a second outer diameter configured to allow ionization of a liquid sample, wherein coating PEEK on the fluid conduit segment and not on the ionization discharge segment causes the second outer diameter of the ionization discharge end to be smaller than the first outer diameter of the liquid connection end; a fluidic pathway fluidically connecting the fluid conduit segment to the ionization discharge segment; and a mechanical connection mechanically connecting the fluid conduit segment to the ionization discharge segment; wherein the liquid connection end of the fluid conduit segment includes an enhanced coating on the at least a portion of the liquid connection end of the fluid conduit segment, the enhanced coating configured to facilitate coating PEEK on the at least a portion of the liquid connection end of the fluid conduit segment that has been coated with the enhanced coating.

2. The electro-spray ionization emitter of claim 1, wherein, The enhanced coating comprises polyimide.

3. The electro-spray ionization emitter of claim 1, wherein, The ionization discharge end is configured to allow electrostatic field effects.

4. The electro-spray ionization emitter of claim 1, wherein, The ionization discharge end includes a pre-treatment surface configured to improve coating of the ionization discharge end with the conductive material.

5. The electro-spray ionization emitter of claim 4, wherein, The ionization discharge end is subjected to ion bombardment by at least one of argon, oxygen, or neon ions to form the pre-treatment surface.

6. The electro-spray ionization emitter of claim 1, wherein, The mechanical connection comprises at least one of a permanent non-deformable and deformable mechanical connection.

7. The electro-spray ionization emitter of claim 6, wherein, The mechanical connection is established using at least one of a clamp or a ferrule.

8. The electro-spray ionization emitter of claim 7, wherein, A position of the at least one of a clamp or a ferrule can be adjusted prior to permanently forming the mechanical connection to ensure accurate positioning of the ionization discharge end within an ionization chamber.

9. The electro-spray ionization emitter of claim 1, wherein, The emitter body includes an electrically insulating material on at least a portion of the fluid conduit segment to allow a user to manipulate the emitter.

10. The electro-spray ionization emitter of claim 1, wherein, The emitter body includes a positioning ring to ensure accurate placement within an ion source housing and, if present, within an aerosolizing gas nozzle.

11. The electrospray ionization emitter of claim 1, further comprising a deformable O-ring to provide an aerosolizing gas seal for gaseous assisted electrospray operation.

12. A method for manufacturing an electrospray ionization emitter, the method comprising: fluidically connecting a fluid conduit segment having a liquid connection end to an ionization discharge segment having an ionization discharge end and mechanically connecting the fluid conduit segment to the ionization discharge segment by a mechanical connection to form an emitter body, the emitter body comprising a fused quartz, the ionization discharge segment fluidically connected to the fluid conduit segment but not in contact with the fluid conduit segment; coating the liquid connection end with a polyether ether ketone (PEEK) on at least a portion of the liquid connection end to form a first outer diameter at the liquid connection end, the first outer diameter allowing the liquid connection end to be connected to a sample source to receive a sample liquid for ionization from the sample source; and coating the ionization discharge end of the ionization discharge segment with a conductive material on at least a portion of the ionization discharge end of the ionization discharge segment, the ionization discharge end having a second outer diameter configured to allow ionization of a liquid sample, wherein coating the fluid conduit segment with PEEK and not coating the ionization discharge segment with PEEK results in the second outer diameter of the ionization discharge end being smaller than the first outer diameter of the liquid connection end, wherein the method further comprises coating the liquid connection end of the fluid conduit segment with an enhanced coating on the at least a portion of the liquid connection end of the fluid conduit segment, the enhanced coating configured to facilitate coating of PEEK on the at least a portion of the liquid connection end of the fluid conduit segment that has been coated with the enhanced coating.

13. The manufacturing method of claim 12, wherein, the enhanced coating comprises a polyimide.

14. The method of manufacture of claim 12, further comprising forming the ionization discharge end to allow for electrostatic field effects.

15. The method of manufacture of claim 12, further comprising pre-treating the ionized surface to improve the coating of the ionization discharge end with the conductive material.

16. The method of manufacture of claim 15, further comprising pre-treating the ionization discharge end by subjecting the ionization discharge end to ion bombardment by at least one of argon, oxygen, or neon ions to form a pre-treated surface.

17. The method of manufacture of claim 12, further comprising permanently forming the mechanical connection between the fluid conduit segment and the ionization discharge segment.

18. The manufacturing method of claim 17, wherein, the mechanical connection between the fluid conduit segment and the ionization discharge segment comprises using at least one of a clamp or a ferrule.

19. The method of manufacture of claim 18, further comprising adjusting a position of the mechanical connection prior to permanently forming the mechanical connection to ensure accurate placement of the emitter discharge segment within an ionization chamber.

20. The method of manufacture of claim 12, further comprising insulating at least a portion of the fluid conduit segment with an electrically insulating material to allow a user to handle the emitter.

21. The method of manufacture of claim 12, further comprising a positioning ring to ensure accurate placement within an ion source housing and, if present, within an aerosolizing gas nozzle.

22. The method of manufacturing of claim 12, further comprising a deformable O-ring to provide an atomizing gas seal for pneumatic assist ejection operation.

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