Electrochemical corrosion-resistant connector for liquid chromatography system

Abstract

To provide an electrochemical corrosion-resistant connector for a liquid chromatography system.SOLUTION: A connector is configured to fluidically couple a first conduit and a second conduit to enable flow of a mobile phase through the conduits for liquid chromatography. The connector includes an electrically-conductive junction for providing, when the electrically-conductive junction is electrically connected with a power source, an electrospray voltage to the mobile phase. The electrically-conductive junction includes a first receptacle having a first sealing surface that interfaces with the mobile phase and fluidically seals with a distal end of the first conduit, a second receptacle having a second sealing surface that interfaces with the mobile phase and fluidically seals with a proximal end of the second conduit, and a through-hole extending from the first receptacle to the second receptacle. The first sealing surface and the second sealing surface each include an electrochemical corrosion-resistant material.SELECTED DRAWING: Figure 6B

Description

[Background technology]

[0001] A mass spectrometer is an instrument that can be used to detect, identify, and / or quantify molecules based on their mass-to-charge ratio (m / z). A mass spectrometer generally includes an ion source for generating ions from components contained in a sample, a mass analyzer for separating the ions based on their m / z, and an ion detector for detecting the separated ions. The mass spectrometer can be connected to a computer-based software platform that uses data from the ion detector to construct a mass spectrum showing the relative abundance of each of the detected ions as a function of m / z. The m / z of the ions can be used to detect and quantify molecules in simple and complex mixtures.

[0002] Ion sources can generate ions from analytes in many different ways. In conventional electrospray ionization (ESI), a liquid sample flows through a small-diameter capillary emitter positioned before the mass analyzer inlet. A high voltage is applied to the liquid sample to generate an electrospray that results in the formation of analyte ions. The analyte ions that enter the mass analyzer inlet are then analyzed by mass spectrometry to generate a mass spectrum of the analyte ions.

[0003] In some examples, components of a sample are separated by liquid chromatography (LC) or the like before ionization and introduction into a mass spectrometer. For example, the analytes are differentially retained on an LC column, allowing the LC system to separate the analytes (e.g., peptides) in the sample over time. The mass spectrometer then acquires a series of mass spectra as the analytes elute from the LC system over time. LC reduces ionization suppression and spectral complexity that would occur if a complex sample were injected directly into a mass spectrometer. Thus, by means of LC, the elution of analytes is dispersed over time before the analytes are introduced into the mass spectrometer. The mass spectra acquired by the mass spectrometer can be used to detect, identify, and / or quantify the analytes in the sample.

[0004] LC systems generally include a chromatography column containing a stationary phase such as a particulate material (e.g., an adsorbent, a gel, etc.) and a pump that delivers a mobile phase such as a solvent (e.g., water, methanol, acetonitrile, etc.) through the chromatography column to separate components in a sample. The outlet of the chromatography column is fluidly connected to the ESI emitter of a mass spectrometer.

[0005] However, the sensitivity, efficiency, stability, and accuracy of the ESI method decrease with prolonged use of the ESI emitter. For example, as the number of sample injections into the LC-MS system increases, the performance of the ESI emitter decreases. Summary of the Invention

[0006] The following presents a simplified summary of one or more aspects of the methods and systems described herein in order to provide a basic understanding of such aspects. This summary is not an extensive overview of all contemplated aspects, and is not intended to identify key or critical elements of all aspects or to delineate the scope of any or all aspects. Its sole purpose is to present some concepts of one or more aspects of the methods and systems described herein in a simplified form as a prelude to the more detailed description that is presented below.

[0007] In some illustrative examples, the connector is configured to fluidly couple a first conduit and a second conduit to allow a mobile phase for liquid chromatography to flow therethrough, the connector comprising a conductive junction for providing an electrospray voltage to the mobile phase when the conductive junction is electrically connected to a power source, the conductive junction comprising: a first receptacle for receiving a distal end of the first conduit, the first receptacle comprising a first sealing surface that interfaces with the mobile phase and fluidically seals with the distal end of the first conduit; a second receptacle for receiving a proximal end of the second conduit, the second receptacle comprising a second sealing surface that interfaces with the mobile phase and fluidically seals with the proximal end of the second conduit; and a through hole extending from the first receptacle to the second receptacle, the first sealing surface and the second sealing surface each comprising an electrochemical corrosion-resistant material.

[0008] In some illustrative examples, a system for analyzing a sample by liquid chromatography-mass spectrometry includes a first conduit, a second conduit, an electrospray ionization (ESI) emitter, and a connector positioned between the first conduit and the second conduit and fluidly coupled to the first conduit and the second conduit to allow a mobile phase to flow through the first conduit and the second conduit to the ESI emitter, the connector including a conductive junction, the conductive junction being a first receptacle for receiving a distal end of the first conduit, the first receptacle including a first sealing surface configured to interface with the mobile phase; The connector comprises: a second receptacle for receiving the proximal end of the second conduit, the second receptacle having a second sealing surface configured to interface with the mobile phase and fluidly seal with the proximal end of the second conduit; a through hole extending from the first receptacle to the second receptacle, the first sealing surface and the second sealing surface each comprising an electrochemical corrosion-resistant material; and a power source electrically connected to the conductive junction to provide an electrospray voltage to the mobile phase.

[0009] In some illustrative examples, a method of making a connector configured to fluidly couple a first conduit and a second conduit to allow a mobile phase for liquid chromatography to flow therethrough includes forming a conductive junction configured to provide an electrospray voltage to the mobile phase when the conductive junction is electrically connected to a power source, the conductive junction including a first receptacle at a proximal end of the connector for receiving a distal end of the first conduit, the first receptacle configured to provide an electrospray voltage to the mobile phase when the conductive junction is electrically connected to a power source ... a first receptacle at the distal end of the connector for receiving the proximal end of the second conduit, the second receptacle having a second sealing surface for interfacing with the mobile phase and fluidly sealing with the proximal end of the second conduit; and a through hole extending from the first receptacle to the second receptacle, wherein the first sealing surface and the second sealing surface each comprise an electrochemically corrosion resistant material. [Brief explanation of the drawings]

[0010] The accompanying drawings illustrate various examples and are a part of this specification. The illustrated examples are merely examples and are not intended to limit the scope of the present disclosure. Throughout the drawings, the same or similar reference numbers refer to the same or similar elements. [Figure 1] 1 shows the functional components of an illustrative liquid chromatography-mass spectrometry (LC-MS) system. [Figure 2] 2 shows the functional components of an illustrative liquid chromatography (LC) system included in the LC-MS system of FIG. 1. [Figure 3] 2 shows a functional diagram of an exemplary ion source included in the LC-MS system of FIG. 1. [Figure 4A] 1 shows an illustrative graph plotting the amount of peptide identified by LC-MS using a particular emitter (e.g., by the LC-MS system of FIG. 1 ) as a function of the number of injections into the LC-MS system using that particular emitter. [Figure 4B] 1 shows an illustrative graph plotting the peak width of a chromatographic peak acquired by LC-MS using a particular emitter (e.g., by the LC-MS system of FIG. 1 ) as a function of the number of injections into the LC-MS system using the particular emitter. [Figure 5A] 1 shows another illustrative graph plotting the amount of peptide identified by LC-MS using a particular emitter (e.g., by the LC-MS system of FIG. 1 ) as a function of the number of injections into the LC-MS system using that particular emitter. [Figure 5B] 1 shows an illustrative graph that may be obtained by LC-MS using a particular emitter (e.g., by the LC-MS system of FIG. 1 ) plotting the resistance of the mobile phase as a function of the number of injections into the LC-MS system using that particular emitter. [Figure 6A] FIG. 1 shows a perspective view of an illustrative electrochemically resistant connector for an LC-MS system. [Figure 6B]FIG. 6A shows a cross-sectional view of the connector of FIG. 6A taken along the dashed line labeled VIB. [Figure 6C] 6B shows a view of the proximal end of the connector of FIG. 6A. [Figure 6D] 6B shows a view of the distal end of the connector of FIG. 6A. [Figure 7A] 6B shows an illustrative configuration of the connector of FIG. 6A coupled with a chromatography column and an electrospray ionization emitter. [Figure 7B] 7B shows a cross-sectional view of the configuration of FIG. 7A. [Figure 8A] 6A shows an illustrative graph plotting the peak width of a chromatographic peak acquired by LC-MS using a particular emitter (e.g., by an LC-MS system including the connector of FIG. 6A) as a function of the number of injections into the LC-MS system using the particular emitter. [Figure 8B] 6A shows an illustrative graph plotting the onset voltage for a particular emitter as a function of the number of injections into an LC-MS system using that particular emitter (eg, an LC-MS system including the connector of FIG. 6A). [Figure 9] 1 shows a cross-sectional view of another illustrative electrochemically resistant connector for an LC-MS system. [Figure 10A] 1 shows a cross-sectional view of an electrochemically resistant connector for an LC-MS system that includes a first material. [Figure 10B] 10B shows a cross-sectional view of the connector of FIG. 10A including a first sealing surface and a second material coated on the first material at the second sealing surface. DETAILED DESCRIPTION OF THE INVENTION

[0011] As described herein, the connector is configured to fluidly connect components of an LC-MS system and, when the ESI emitter is non-conductive, to provide a liquid-metal interface for applying an electrospray voltage to the mobile phase. In some illustrative examples, the connector comprises a conductive junction that interfaces with the mobile phase to provide an electrospray voltage to the mobile phase when the conductive junction is electrically connected to a power source. The conductive junction comprises a first receptacle for receiving a distal end of a first conduit (e.g., a conduit included in or fluidly coupled to a chromatography column), a second receptacle for receiving a proximal end of a second conduit (e.g., a conduit included in or fluidly coupled to an ESI emitter), and a through-hole extending from the first receptacle to the second receptacle to allow the mobile phase to flow therethrough. The conductive joints comprise electrochemically corrosion resistant materials, which reduce or eliminate electrochemical corrosion at the sealing surfaces, thus helping to extend the usable life of the ESI emitter compared to conventional connectors for LC-MS, and helping to improve the sensitivity and resolution of ESI-based LC-MS methods.

[0012] The systems and methods described herein can be implemented in conjunction with a liquid chromatography-mass spectrometry (LC-MS) system. FIG. 1 shows functional components of an illustrative LC-MS system 100. As shown, the LC-MS system 100 includes a liquid chromatography (LC) system 102 and a mass spectrometer 104. The LC system 102 is configured to separate components of a sample and deliver those components to the mass spectrometer 104 for mass analysis by the mass spectrometer 104. In some examples, the LC system 102 can also detect the relative abundance of the separated components, such as by generating a chromatogram representing the components in the sample. The illustrative LC system 102 is described in further detail below with reference to FIG. 2.

[0013] The mass spectrometer 104 includes an ion source 106, a mass analyzer 108, and a controller 110. The mass spectrometer 104 may further include any additional or alternative components (not shown) as may be suitable for a particular implementation (e.g., ion optics, filters, autosamplers, etc.).

[0014] The ion source 106 is configured to generate an ion stream 112 of ions from the sample by electrospray ionization (ESI) and deliver the ions to the mass analyzer 108. An illustrative ion source is described in further detail below with reference to FIG.

[0015] The mass analyzer 108 is configured to receive the ion stream 112 and separate the ions according to their respective m / z. The mass analyzer 108 may be implemented by any suitable mass analyzer, such as a quadrupole mass filter, an ion trap (e.g., a three-dimensional quadrupole ion trap, a cylindrical ion trap, a linear quadrupole ion trap, a toroidal ion trap, etc.), a time-of-flight (TOF) mass analyzer, an electrostatic trap mass analyzer (e.g., an orbital electrostatic trap, such as an Orbitrap mass analyzer, a Kingdon trap, an electrostatic linear ion trap), a Fourier transform ion cyclotron resonance (FT-ICR) mass analyzer, a sector mass analyzer, etc.

[0016] The ion detector (not shown) is configured to detect ions at each of a variety of different m / z and, in response, generate an electrical signal representative of the ion intensity. The electrical signal is transmitted to the controller 110 for processing, such as constructing a mass spectrum of the sample. For example, the mass analyzer 108 may emit an ejected beam of separated ions to the ion detector, which is configured to detect the ions in the ejected beam and generate or provide data that can be used by the controller 110 to construct a mass spectrum of the sample. The ion detector may be implemented by any suitable detection device, including, but not limited to, an electron multiplier, a Faraday cup, or the like.

[0017] A controller 110 may be communicatively coupled to and configured to control the operation of the LC-MS system 100. For example, the controller 110 may be configured to control the operation of various hardware components included in the LC system 102, the ion source 106, the mass analyzer 108, and / or the detector. Illustratively, the controller 110 may be configured to control the amount of mobile phase pumped through the LC system 102, control the high voltage applied to the connectors of the LC system 102, control the accumulation time of the mass analyzer 108, control the oscillating voltage power supply and / or the DC power supply to supply RF and / or DC voltage to the mass analyzer 108, adjust the values ​​of the RF and DC voltages to select a valid m / z (including a mass tolerance window) for analysis, and adjust the sensitivity of the ion detector (e.g., by adjusting the detector gain).

[0018] Unless otherwise specified or indicated by context, the terms "a," "an," and "the" mean "one or more." For example, "a molecule" should be interpreted as meaning "one or more molecules."

[0019] As used herein, "about" and "substantially" will vary to some extent as understood by those of ordinary skill in the art and given the context in which they are used. If there are uses of the terms that are not clear to persons of ordinary skill in the art given the context in which the terms are used, "about" and "substantially" will mean up to 10% of the particular value.

[0020] 2 shows functional components of an illustrative implementation 200 of an LC system 102. As shown, the LC system 102 includes a mobile phase source 202, a pump 204, a chromatography column 206 (“column 206”), and a connector 208. FIG. 2 is merely illustrative, as the LC system 102 may have other suitable configurations. The LC system 102 may also include additional or alternative components (e.g., a detector, a degassing unit, an injector, a column oven, etc.) not shown in FIG. 2 , as may be useful for a particular implementation.

[0021] The mobile phase source 202 accepts an injection of the sample 210 and provides a mobile phase that flows through the column 206 and connector 208 to transport the sample 210 to the ion source 106 of the mass spectrometer 104. The mobile phase may include a solvent such as water, methanol, or acetonitrile. In some examples, the mobile phase flows through the LC system 102 at a flow rate ranging from about 1 microliter (μL) per minute (1 μL / min) to about 1 milliliter (mL) per minute (1 mL / min). For nanospray ionization (NSI), the mobile phase may flow through the LC system 102 at a nanoscale flow rate ranging from about 10-50 nanoliters (nL) per minute (10-50 nL / min) to about 1000-1500 nL / min. The sample 210 may include, for example, chemical components (eg, molecules, ions, etc.) and / or biological components (eg, metabolites, proteins, lipids, etc.) for detection and analysis by the LC-MS system 100 .

[0022] The pump 204 is fluidly coupled to the mobile phase source 202 and configured to pump the mobile phase through the column 206 and the connector 208 to the ion source 106. Illustratively, the pump 204 is configured to deliver the mobile phase to the column 206 and / or the connector 208 at a steady (e.g., substantially constant) flow rate. In some examples, the pump 204 includes at least a pair of reciprocating pistons, such that a first piston delivers flow and a second piston aspirates the mobile phase at the steady flow rate. The pump may be implemented by any suitable pumping device, including, but not limited to, a reciprocating pump, a syringe pump, a binary pump, a constant pressure pump, a quaternary pump, etc. In some examples, the pump 204 may be communicatively coupled to the controller 110, such that the controller 110 is configured to control the flow rate of the mobile phase delivered by the pump 204. Additionally, the flow rate of the pump 204 may be programmable, such as by using a user interface of the controller 110.

[0023] Column 206 is configured to receive the mobile phase delivered by pump 204. Column 206 includes a stationary phase, such as a particulate material (e.g., an adsorbent, a gel, a porous solid (glass, silica, alumina, etc.)). In some examples, the stationary phase is bound or absorbed to an interior surface within an opening of column 206 and / or packed within the opening of column 206. The stationary phase is configured to differentially interact with components of sample 210 in the mobile phase to separate the components of sample 210 based on, for example, the size of the components, their affinity for the stationary phase, their polarity, and / or their hydrophobicity.

[0024] The mobile phase flows from the column 206 to the ion source 106, which ionizes the analytes in the mobile phase and directs the ions into the mass analyzer 108. In the example described herein, the ion source 106 ionizes the analytes by electrospray ionization. Electrospray ionization is performed by pumping the mobile phase through the emitter of the ion source 106 and applying an electrospray voltage to the mobile phase to generate an ion spray from the tip of the emitter. The emitter can be either conductive (e.g., stainless steel) or non-conductive (e.g., glass). For conductive emitters, a high potential difference of approximately 1 kV to 5 kV is maintained between the emitter, which acts as a counter electrode, and the mass analyzer inlet. For non-conductive emitters, a liquid-metal junction is positioned upstream of the emitter tip to apply the electrospray voltage to the mobile phase, thereby conveying the electrospray voltage to the emitter tip via the conductivity of the mobile phase.

[0025] The connector 208 is configured to fluidly connect the components of the LC-MS system 100 to provide a liquid-metal interface for applying an electrospray voltage to the mobile phase when the emitter is non-conductive. As shown, the connector 208 is positioned between the column 206 and the ion source 106 to fluidly connect the LC system 102 with the ion source 106. However, in other examples (not shown in FIG. 2 ), the connector 208 can be positioned elsewhere in the LC system 102 and used to fluidly connect other components of the LC-MS system 100. For example, the connector 208 can be positioned upstream of the column 206 such that the connector 208 fluidly connects the pump 204 with the column 206. Additionally or alternatively, the column 206 and / or the connector 208 can be positioned within the ion source 106.

[0026] As described in further detail below, connector 208 includes a conductive junction having a first receptacle for receiving a first conduit (e.g., contained in or fluidly coupled to column 206), a second receptacle for receiving a second conduit (e.g., contained in or fluidly coupled to ion source 106), and a through-hole extending from the first receptacle to the second receptacle for allowing mobile phase to flow therethrough. The conductive junction may be integral with and / or inserted within connector 208.

[0027] The conductive junction of connector 208 interfaces with the mobile phase and comprises a conductive material such that the conductive junction is configured to provide an electrospray voltage (e.g., about 2-6 kilovolts (kV) for ESI, or about 0.7-3.5 kV for NSI) to the mobile phase when the junction is electrically coupled to a power source 212. The conductive junction may be connected to the power source 212 via a high-voltage line 214 (e.g., an electrical cable or other wiring or electrical connection). The electrospray voltage may be carried by the mobile phase to the ESI emitter of the ion source 106.

[0028] 3 shows a functional diagram of an illustrative implementation 300 of an interface between an ion source 106 and a mass analyzer 108. The ion source 106 and the mass analyzer 108 may have other suitable configurations, and thus FIG. 3 is merely illustrative. As shown, the ion source 106 includes an ESI emitter 302. The ion source 106 may also include additional or alternative components not shown in FIG. 3 , such as a positioning system, a voltage source, a housing (e.g., that houses components of the ion source 106 and / or that attaches to the mass analyzer 108), a camera, an adapter, a lock, mounting components, gas supply lines, etc., as may be useful for a particular implementation.

[0029] The emitter 302 may be implemented by a needle or capillary configured for electrospray ionization. The emitter 302 may be formed of a non-conductive material such as glass, borosilicate, or any other suitable material and may be coated with an outer coating such as a polyimide or other polymer coating. In some examples, the emitter 302 is configured for low ESI flow rates (e.g., about 10-50 nL / min up to about 1000-1500 nL / min). In other examples, the emitter 302 is configured for capillary flow rates (e.g., about 1 μL / min up to about 10-20 μL / min), microflow rates (e.g., about 10 μL / min up to about 100 μL / min), or conventional ESI analytical flow rates (e.g., greater than about 50 μL / min). The emitter 302 may be contained within an emitter cartridge, which may include, without limitation, a mounting unit for holding the emitter 302, an adapter for connecting or integrating the emitter 302 with the LC system 102, on-board non-volatile memory (which may store position data and / or other data that may be used for positioning the emitter 302), and / or any other suitable components. In some examples in which the emitter cartridge includes on-board memory, the emitter cartridge may be communicatively coupled to the controller 110, such as via a wired or wireless connection.

[0030] The LC system 102 provides a mobile phase that flows through an emitter 302. An electrospray voltage is applied (e.g., via high-voltage wire 214) to a metal junction in a connector 208 that interfaces with the liquid mobile phase. The electrospray voltage is carried by the mobile phase to the tip 304 of the emitter 302. The electrospray voltage generates a strong electric field at the tip 304 of the emitter 302. The electric field induces ion movement in the mobile phase as ions are emitted from the tip 304 of the emitter 302, resulting in electrohydrodynamic breakdown of the mobile phase, generation of charged droplets, and formation of a spray plume 306 that moves toward an inlet 308 of the mass analyzer 108. As the spray plume 306 moves toward the inlet 308, solvent evaporates from the charged droplets, gradually increasing the charge intensity on the surface of the droplets until the droplets split into one or more electrically charged ions. The electrically charged phase ions are then introduced into the inlet 308 of the mass analyzer 108 by application of an electric field, a vacuum at the inlet, and a sheath gas, if present, at the emitter 302 .

[0031] In some examples, the emitter 302 is inserted into a nozzle 310, and a sheath gas, such as nitrogen gas (N), flows coaxially around the emitter 302 within the nozzle 310. As the mobile phase exits the tip 304, the sheath gas exits the distal end of the nozzle 310 and flows around the spray plume 306, thereby controlling the position, shape, and direction of the spray plume 306 and reducing mass stratification. The sheath gas flow rate can be adjusted to achieve a desired position and shape of the spray plume 306. The sheath gas can also reduce the surface tension barrier to initiate spray plume 306 formation. In a further example, a heated auxiliary gas can be used to assist in desolvation of charged droplets in the spray plume 306. However, at low flow rates (e.g., nanoflow), good sensitivity can be obtained without a sheath gas and / or auxiliary gas.

[0032] In some examples, the positioning system 312 is configured to hold the tip 304 of the emitter 302 a controlled distance (e.g., about 0.1-3 cm) from the inlet 308 of the mass analyzer 108. Additionally, as shown in FIG. 3, the emitter 302 is angled relative to the longitudinal axis of the inlet 308. Any suitable angle can be used (e.g., 45°, 30°, 22.5°, 15°, etc.). In other examples, the emitter 302 is not angled relative to the longitudinal axis of the inlet 308, but is positioned such that the longitudinal axes of the emitter 302 and the inlet 308 are substantially parallel. The inlet 308 is shown adjacent to the mass analyzer 108 for illustrative purposes only. It will be appreciated that various other components may be positioned between the inlet 308 and the mass analyzer 108, such as, but not limited to, ion optics, an ion guide, an ion trap, an ion mobility separator, a filter, and / or a collision cell. The inlet 308 may have any suitable configuration, such as an orifice or a capillary (e.g., an ion transfer tube such as a circular bore ion transfer tube (ITT) or a high capacity transfer tube (HCTT) such as a letterbox inlet). In an alternative example, the inlet 308 is a field asymmetric ion mobility spectrometry (FAIMS) inlet orifice, with the FAIMS electrodes positioned immediately before the entrance to the mass analyzer. When the emitter 302 is mounted to the positioning system 312, the positioning system 312 may automatically adjust the position of the emitter 302 (e.g., the position of the tip 304) relative to the inlet 308.

[0033] The mass analyzer 108 receives the analyte ions in the spray plume 306 that enter the inlet 308 and performs mass analysis of the analyte ions. As described above, the controller 110 can process the received signals and construct a mass spectrum of the ions introduced into the inlet 308 based on signals detected by an ion detector within the mass analyzer 108.

[0034] As mentioned above, the performance of the emitter 302 decreases as emitter 302 usage increases. LC-MS experiments were performed to evaluate the change in performance with emitter aging, and the results are shown in the plots of Figures 4A and 4B. The experiment included a sequence of 500 injections of 1 μg of HeLa cell digest. In addition, the sequence included one blank run every five injections, resulting in a total of 575 injections. Therefore, when counting the blank and run runs, the emitter underwent approximately 20% additional injections that are not reflected in the plots shown in Figures 4A and 4B. A 200 ng HeLa load was used in the LC-MS experiments. A connector containing titanium junctions fluidly connected the emitter to the LC column. For each sample injection, an electrospray voltage was applied to the mobile phase through the titanium junction in the connector to form a spray plume of ions for mass analysis (e.g., to identify multiple peptides in the sample). 4A shows an illustrative graph 400 plotting the amount of peptides identified by LC-MS using the emitter (e.g., by the LC-MS system of FIG. 1) as a function of the number of injections into the LC-MS system using the emitter. As shown in FIG. 4A, the number of peptides reliably identified by LC-MS analysis decreased as the number of injections into the LC-MS system increased, which was attributed to the degradation of the emitter with increasing number of injections.

[0035] FIG. 4B shows an illustrative graph 402 plotting the peak width of the chromatographic peak obtained by the LC-MS analysis of FIG. 4A using the emitter as a function of the number of injections into the LC-MS system using the emitter. The peak width of the chromatographic peak was measured in full-width half-maximum (FWHM). As shown, the width of the chromatographic peak broadened as the number of injections introduced into the LC-MS system increased, which was attributed to emitter degradation. Such chromatographic peak broadening can reduce the performance of the LC-MS system and make it difficult to distinguish peptides in the sample.

[0036] The inventors hoped to identify the root cause of the performance decline and design an emitter device with improved lifetime. In effect, ESI is a two-electrode, controlled-current electrochemical cell. In the case of a conductive emitter, the emitter is the working electrode, and the mass spectrometer inlet is the counter electrode. The emitter also serves as the current-controlled source. The rate of charged droplet generation by the ion source determines the average current flowing through the cell. In the positive mode, oxidation reactions occur within the ESI emitter. The current generated from the source creates an interfacial potential at the working electrode. The current density on the working electrode affects the interfacial potential, which ultimately determines which reactions are possible in the system and the rate at which they occur. Differences in working electrode materials are most apparent at low current densities. In the case of a stainless steel emitter, low anodic currents drive reactions involving iron corrosion, while at higher current densities, the interfacial potential increases, oxidizing other species in the system, including the solvent. Therefore, the physical location of the electrochemical reaction and the electrode material can affect the mass spectrum. For example, in pulled static nanospray emitters, where electrochemistry occurs in the same physical space as the sample, mass spectra can often become time-dependent as concentration of electrochemical products occurs. Alternatively, anodic corrosion of zinc and stainless steel emitters, respectively, can result in the appearance of Zn in the mass spectra. 2+ ions and Fe 2+ It has been shown that electrochemical reactions produce ions, however determining the exact nature and extent of these reactions is often a difficult problem.

[0037] In the experiments described with reference to Figures 4A and 4B, we noticed that deposits formed on the emitter tip with increasing usage. Therefore, we performed LC-MS experiments to evaluate whether cleaning the emitter tip would improve emitter performance and extend emitter lifetime, the results of which are shown in the plots of Figures 5A and 5B. The experiment included a sequence of 200 injections of 1 μg of HeLa cell digest. In addition, the sequence included one blank run every five injections. Therefore, counting the blank and run runs, the emitter received approximately 20% additional injections that are not reflected in the plots shown in Figures 5A and 5B. A 200 ng HeLa load was used in the LC-MS experiments.

[0038] Figure 5A shows an illustrative graph 500 plotting the amount of peptides identified by LC-MS using a particular emitter as a function of the number of injections into the LC-MS system with that emitter. As shown, the number of peptides identified by the LC-MS system decreased as the number of injections into the LC-MS system increased, which was attributed to emitter degradation. Based on visual observation of the emitter, we suspected that the deterioration in emitter performance might be caused by deposits (e.g., analyte ions, solvent ions, ambient ions, electrochemical products, etc.) accumulated on the emitter. Therefore, the emitter was cleaned to remove the deposits. The cleaning included ultrasonically cleaning the emitter for approximately 60 minutes and soaking the emitter in a sodium hydroxide solution (e.g., a solution containing 12 moles of sodium hydroxide per liter of solution (12 M NaOH)) overnight. After cleaning the emitter, the sample was again injected into the LC-MS system using the same emitter with fewer injections. However, the number of peptides identified by the LC-MS system did not increase significantly after emitter cleaning, indicating that the decrease in performance was not due to deposits accumulated on the exterior of the emitter.

[0039] 5B shows an illustrative graph 502 plotting the electrical resistance of the mobile phase obtained by the LC-MS analysis of FIG. 5A using the same emitter as a function of the number of injections into the LC-MS system using the same emitter. As shown, the resistance of the mobile phase (e.g., approximately 99% water containing 0.1% formic acid) decreased as the number of injections into the LC-MS system increased, which was attributed to emitter degradation. The resistance of the mobile phase in the LC-MS system, as well as the number of peptides identified by the LC-MS system, did not increase significantly after cleaning the emitter, further indicating that emitter degradation was not due to deposits accumulated on the outside of the emitter.

[0040] Because cleaning the emitter to remove deposits accumulated on its exterior failed to significantly improve emitter performance, based on mobile-phase resistance measurements, we investigated whether the decrease in performance due to emitter aging could be linked to electrochemical reactions occurring internally within the mobile-phase flow path. We found that in the case of non-conductive emitter configurations, electrochemical reactions likely occurred upstream of the emitter at the liquid-metal interface of titanium junctions in connectors included in LC-MS systems. Conventional connectors use titanium as a conductive junction because it allows for reproducible machining of small through-holes (approximately 50 μm in inner diameter and 0.5 mm in length) for fluid flow through the junction. The titanium junction interfaces with the mobile phase and provides an electrospray voltage to the mobile phase. The electric field generated by the electrospray voltage concentrates positively charged ions near the mobile-phase liquid meniscus. When Coulomb forces are sufficient to overcome the surface tension of the mobile phase, positively charged droplets are formed. Due to the loss of positive charge via droplet generation, electron transfer reactions (e.g., electrochemical reactions such as oxidation) involving mobile phase ions occur at the liquid-metal interface of the connector. Such electron transfer reactions electrochemically corrode the liquid-metal interface of the highly electronegative titanium junction of the connector, thus creating or increasing dead volume within the connector, adding contaminants to the mobile phase, and forming deposits on the interior surfaces of the emitter, all of which can cause emitter degradation, reduce emitter performance over time, and / or contaminate mass spectra produced by the mass spectrometer.

[0041] To prevent these problems, the liquid-metal interface of a connector included in an LC-MS system can include an electrochemical corrosion-resistant material. In some illustrative examples, the connector is configured to fluidly couple a first conduit (e.g., included in or fluidly coupled to a chromatography column) and a second conduit (e.g., included in or fluidly coupled to an ESI emitter) to allow a mobile phase for liquid chromatography to flow therethrough. The connector includes a conductive junction for providing an electrospray voltage to the mobile phase when the conductive junction is electrically connected to a power source. The conductive junction includes a first receptacle for receiving the distal end of the first conduit, a second receptacle for receiving the proximal end of the second conduit, and a through-hole extending from the first receptacle to the second receptacle. The conductive junction includes an electrochemical corrosion-resistant material.

[0042] The systems, devices, and apparatus described herein provide various benefits, which may include one or more advantages over conventional LC-MS systems and connectors. For example, the systems, devices, and apparatus described herein include electrochemically corrosion-resistant materials at the conductive joints of the connectors. Additionally, the systems, devices, and apparatus described herein may be configured to reduce and / or prevent electrochemical reactions at the conductive joints, thereby reducing and / or preventing connector corrosion and / or emitter degradation. Reducing and / or preventing connector corrosion and / or emitter degradation may further reduce and / or prevent a decrease in sensitivity, efficiency, stability, and accuracy of ESI methods in LC-MS systems that include electrochemically corrosion-resistant materials (e.g., by reducing and / or preventing contamination of the mobile phase with electrochemical products, broadening of chromatographic peaks, and / or a decrease in ion identity in mass spectra).

[0043] Various illustrative examples will now be described in further detail with reference to the drawings. The systems, devices, and apparatus described herein may provide the advantages noted above and / or various additional and / or alternative advantages set forth herein.

[0044] 6A-6D show various views of an illustrative implementation of an electrochemically resistive connector 208 for an LC-MS system (e.g., LC-MS system 100). FIG. 6A shows a perspective view of connector 208. FIG. 6B shows a cross-sectional view of connector 208 taken along the dashed-dotted line labeled VIB in FIG. 6A. FIGS. 6C and 6D show views of the proximal and distal ends, respectively, of connector 208. As used herein, proximal refers to the upstream side of connector 208, and distal refers to the downstream side of connector 208. However, it will be appreciated that in some examples, connector 208 is symmetrical and thus can be connected in any orientation.

[0045] 6A-6D, connector 208 comprises an outer sheath material 600 and a conductive joint 602 extending within outer sheath material 600. Although outer sheath material 600 is shown as having an elongated cylindrical shape, other suitable shapes for outer sheath material 600 (e.g., a cube, a prism, a cone, etc.) may be used. In some examples, outer sheath material 600 includes a grip 604 having one or more flat surfaces configured to facilitate coupling of connector 208 to other components of an LC-MS system (e.g., one or more conduits included in the LC-MS system).

[0046] Junction 602 comprises a first receptacle 606-1 for receiving a first conduit (e.g., a conduit included in or fluidly coupled to column 206), a second receptacle 606-2 for receiving a second conduit (e.g., a conduit included in or fluidly coupled to emitter 302), and a through-hole 608 extending between first receptacle 606-1 and second receptacle 606-2 to allow mobile phase flow therethrough. In the illustrated example, a portion of each receptacle 606 is conical in shape narrowing toward through-hole 608, which may facilitate receiving and / or coupling a conduit therein. However, receptacles 606 may include other suitable shapes (e.g., cylindrical, cubical, prismatic, etc.). For example, the receptacles 606 may have a constant diameter such that the receptacles 606 do not narrow toward the through-holes 608. In some examples, each receptacle 606 includes threads 610 to facilitate receiving and / or coupling a conduit therein. As shown in FIG. 6B, the joint 602 is integral with the outer sheath material 600. In other examples (not shown), the joint 602 is separate from the outer sheath material 600 but is mounted or located within the outer sheath material 600.

[0047] The junction 602 further includes a first sealing surface 612-1 in the first receptacle 606-1 and a second sealing surface 612-2 in the second receptacle 606-2. The first sealing surface 612-1 is configured to interface with the mobile phase and to fluidly seal with the distal end of the first conduit. For example, the first sealing surface 612-1 extends inward into the first receptacle 606-1 at the distal end 616 of the first receptacle 606-1 such that the distal end of the first conduit is configured to abut or be positioned near the first sealing surface 612-1 when the first conduit is positioned within the first receptacle 606-1. Similarly, the second sealing surface 612-2 is configured to interface with the mobile phase and to fluidly seal with the proximal end of the second conduit. For example, the second sealing surface 612-2 extends inwardly into the second receptacle 606-2 at the proximal end 618 of the second receptacle 606-2 such that when the second conduit is positioned in the second receptacle 606-2, the proximal end of the second conduit is configured to abut or be positioned near the second sealing surface 612-2.

[0048] Junction 602 includes an electrically conductive first material (e.g., titanium) such that, when junction 602 is electrically coupled to a power source, junction 602 is configured to provide an electrospray voltage to the mobile phase through a liquid-metal interface of junction 602 (e.g., at sealing surface 612 and / or within through-hole 608). Junction 602 also includes a second material at first sealing surface 612-1 and second sealing surface 612-2. The second material is an electrochemical corrosion resistant material such that the second material is configured to reduce and / or prevent electrochemical reactions at junction 602 and / or electrochemical corrosion at junction 602 (e.g., at sealing surface 612). As shown, the second material is a coating 614 on the first material at first sealing surface 612-1 and second sealing surface 612-2. Coating 614 may be applied to sealing surface 612 by any suitable technique, such as electroplating, sputter coating, chemical vapor deposition (CVD), electron beam evaporation, thin film deposition, etc. Other suitable configurations for including a galvanic corrosion resistant material in joint 602 may be used. For example, coating 614 may also be applied to additional surfaces of joint 602, such as the interior surfaces of through-holes 608. Additionally or alternatively, joint 602 may be formed entirely from a galvanic corrosion resistant material, as described in further detail below.

[0049] An electrochemically corrosion-resistant material is a conductive material that has a standard reduction potential that is greater (e.g., more positive) than a threshold standard reduction potential. The standard reduction potential of a species represents the tendency of the species to be reduced. The standard reduction potential is measured as the potential difference between the cathode and anode of an electrochemical cell, where the anode is a standard hydrogen electrode (SHE) and the cathode is formed by the species being measured. The standard reduction potential of a species is measured at a temperature of 298 K, a pressure of 1 atmosphere, and in a 1 molar (M) solution. In some examples, the threshold standard reduction potential is the reduction potential of the standard hydrogen electrode (SHE) (e.g., 0 volts (V)). In other examples, the threshold standard reduction potential is the standard reduction potential of titanium (e.g., −1.6 V). In other further examples, the threshold standard reduction potential is −1.0V, −0.5V, −0.3V, −0.25V, −0.1V, +0.1V, +0.25V, +0.5V, +0.75V, or +1.0V.

[0050] In some examples, the electrochemical corrosion-resistant material includes a noble metal. As used herein, noble metals include platinum group metals (ruthenium, rhodium, palladium, osmium, iridium, platinum), gold, silver, copper, rhenium, and mercury. The platinum group metals, silver, gold, and mercury all have standard reduction potentials greater than about 0.6 V, and copper and rhenium have standard reduction potentials greater than about 0.25 V. Additionally or alternatively, the electrochemical corrosion-resistant material includes cobalt or nickel, which have standard reduction potentials greater than −0.30. Additionally or alternatively, the electrochemical corrosion-resistant material includes stainless steel, such as 904L stainless steel. While 904L stainless steel is not completely corrosion-resistant, 904L stainless steel significantly reduces electrochemical corrosion compared to titanium. In some examples, the electrochemically corrosion-resistant material comprises a metal alloy comprising greater than about ten percent (10%) nickel, greater than about fifteen percent (15%) nickel, greater than about twenty percent (20%) nickel, greater than about twenty-five percent (25%) nickel, or greater than about thirty percent (30%) nickel by weight. Additionally or alternatively, the electrochemically corrosion-resistant material comprises a metal alloy comprising less than about five percent (5%) iron, less than about three percent (3%) iron, or less than about one percent (1%) iron by weight. In some examples, the electrochemically corrosion-resistant material comprises a metal alloy comprising greater than about twenty percent (20%) nickel and less than about one percent (1%) iron by weight.

[0051] 7A and 7B show an illustrative configuration 700 of a connector 208 coupled to a column 206 and an emitter 302 via conduits 702 (e.g., conduits 702-1 and 702-2). As shown, the column 206 is coupled to a proximal end of a first conduit 702-1 such that an opening 704 of the column 206 is fluidly coupled with a first opening 706-1 extending through the first conduit 702-1, allowing a mobile phase to flow therethrough. The first conduit 702-1 extends from the column 206 to the connector 208 such that a distal end of the first conduit 702-1 is received within a first receptacle 606-1 of the connector 208, fluidly coupling the first opening 706-1 of the first conduit 702-1 with the through-hole 608, allowing a mobile phase to flow therethrough. Furthermore, the distal end of the first conduit 702-1 is positioned against the first sealing surface 612-1 of the first receptacle 606-1, such that the first sealing surface 612-1 fluidly seals with the proximal end of the first conduit 702-1 (to prevent the mobile phase from leaking out of the connector 208) and interfaces with the mobile phase.

[0052] Similarly, the emitter 302 is coupled to a distal end of the second conduit 702-2 such that the capillary tube 708 of the emitter 302 is fluidly coupled to a second opening 706-2 extending through the second conduit 702-2, allowing the flow of mobile phase therethrough. The second conduit 702-2 extends from the emitter 302 to the connector 208 such that a proximal end of the second conduit 702-2 is received within a second receptacle 606-2 of the connector 208, fluidly coupling the second opening 706-2 of the second conduit 702-2 with the through-hole 608, allowing the flow of mobile phase therethrough. Additionally, the proximal end of the second conduit 702-2 is positioned against the second sealing surface 612-2 of the second receptacle 606-2, such that the second sealing surface 612-2 fluidly seals with the distal end of the second conduit 702-2 (to prevent the mobile phase from leaking out of the connector 208) and interfaces with the mobile phase. Thus, the connector 208 is configured to fluidly couple the column 206 with the emitter 302 to allow the mobile phase to flow from the column 206 to the emitter 302.

[0053] 7A and 7B show connector 208 positioned between column 206 and emitter 302, in other examples (not shown in FIGS. 7A and 7B), connector 208 is positioned elsewhere within LC system 102 and used to fluidly connect other components of LC-MS system 100. For example, connector 208 may additionally or alternatively be positioned upstream of column 206, such that connector 208 fluidly connects pump 204 with column 206.

[0054] In some examples, connector 208 is a dead volume-free (or zero dead volume (ZDV)) connector. Illustratively, the distal end of first conduit 702-1 may abut first sealing surface 612-1, and the proximal end of second conduit 702-2 may abut second sealing surface 612-2, such that there is substantially no unswept volume within connector 208 that receives mobile phase between the distal end of first conduit 702-1 and first sealing surface 612-1, or between the proximal end of second conduit 702-2 and second sealing surface 612-2. Alternatively, connector 208 may be a low dead volume connector. For example, the distal end of the first conduit 702-1 may be positioned near the first sealing surface 612-1 and the proximal end of the second conduit 702-2 may be positioned near the second sealing surface 612-2, such that there is a low volume (e.g., less than about 500 nL, less than about 100 nL, less than about 50 nL, less than about 1 nL, etc.) within the connector 208 for receiving the mobile phase between the distal end of the first conduit 702-1 and the first sealing surface 612-1 and / or between the proximal end of the second conduit 702-2 and the second sealing surface 612-2.

[0055] In the illustrated example, each conduit 702 includes a coupling 710 positioned at an end portion of each conduit 702 received in a respective receptacle 606 of the connector 208 and configured to couple each conduit 702 with the connector 208. For example, each coupling may include a ferrule, a Viper fitting, a seal (e.g., a polyetheretherketone (PEEK) seal), etc. As shown, each coupling 710 is threaded into its respective receptacle 606, for example, by rotating the connector 208 relative to the respective coupling 710 (e.g., a user may grasp a nut 712 positioned on each conduit 702 and a grip 604 of the connector 208 and rotate the connector 208 relative to the respective coupling 710 to thread each coupling 710 onto the connector 208). Each coupling 710 is positioned a selected distance away from the end of each conduit 702 such that when each coupling 710 is positioned within its respective receptacle 606, the end of each conduit 702 is configured to fluidly seal with a respective sealing surface 612 of the connector 208. While the illustrated example shows the coupling 710 threaded into the receptacle 606, alternative configurations (e.g., friction fit, snap fit, etc.) may be used to fluidly couple the conduits 702 with the connector 208. As shown, as the mobile phase 714 flows through the first conduit 702-1, the connector 208, and the second conduit 702-2, the mobile phase 714 interfaces with the sealing surface 612. In some examples, the conduit 702 can recede away from the sealing surface 612, which may result in an unswept volume (e.g., dead volume) of the mobile phase 714 between the first sealing surface 612-1 and the first conduit 702-1 and / or between the second sealing surface 612-2 and the second conduit 702-2. Such an unswept volume of the mobile phase 714 in a no-dead-volume and / or low-dead-volume connector may result in broader chromatographic peaks.

[0056] We investigated whether applying electrochemical corrosion-resistant materials to the first and second sealing surfaces of the connector would improve emitter performance and extend emitter life. LC-MS experiments were performed to evaluate changes in emitter performance with aging, as shown in the plots in Figures 8A and 8B. The experiment involved a sequence of 500 injections of 1 μg of HeLa cell digest. In addition, the sequence included one blank run every five injections, resulting in a total of 575 injections. Therefore, counting the blank and run runs, the emitter underwent approximately 20% additional injections that are not reflected in the plots shown in Figures 8A and 8B. A 200 ng HeLa load was used in the LC-MS experiments. Various connectors containing conductive junctions fluidly connected the emitter to the LC column. For each sample injection, an electrospray voltage was applied to the mobile phase through the conductive junctions in the connector to form a spray plume of ions for mass analysis (e.g., to identify multiple peptides within the sample).

[0057] 8A and 8B illustrate the effect of including an electrochemical corrosion-resistant material on the sealing surfaces of various connectors. FIG. 8A shows an illustrative graph 800 plotting the peak width of a chromatographic peak acquired by LC-MS using each emitter as a function of the number of injections into the LC-MS system using each emitter. The peak width of the chromatographic peak was measured in full width at half maximum (FWHM). As shown, in a first experiment performed using a first connector having a titanium junction without an electrochemical corrosion-resistant material on the sealing surface, the width of the chromatographic peak increased as the number of injections introduced into the LC-MS system increased (e.g., as shown by the solid line marked with black circles). In a second experiment performed using a second connector including a titanium junction with a gold electrochemical corrosion-resistant material on the sealing surface of the junction, the width of the chromatographic peak increased slightly as the number of injections introduced into the LC-MS system increased (e.g., as shown by the dash-dotted line marked with open triangles). However, the width of the chromatographic peaks in the second experiment performed with the second connector was not as broad as the width of the chromatographic peaks in the first experiment performed with the first connector, which is believed to be due to the gold electrochemical corrosion-resistant material included in the sealing surface of the second connector. Additionally, in the third experiment performed with a third connector having a 904L stainless steel electrochemical corrosion-resistant material included in the sealing surface of the conductive joint, the width of the chromatographic peaks did not broaden (e.g., as shown by the dashed line marked with an "x") as the number of injections introduced into the LC-MS system increased, which is believed to be due to the 904L stainless steel electrochemical corrosion-resistant material included in the sealing surface of the third connector.

[0058] The reduction and / or elimination of chromatographic peak broadening using second and third connectors having an electrochemical corrosion resistant material on the sealing surfaces of the titanium joints indicates that the electrochemical corrosion resistant material included on the sealing surfaces of the titanium joints reduces and / or eliminates corrosion of the joints and therefore degradation of the emitter over long-term use.

[0059] 8B shows an illustrative graph 802 plotting the amount of peptides identified by the LC-MS analysis of FIG. 8A using each emitter as a function of the number of injections into the LC-MS system using each emitter. As shown, in a first experiment performed using a first connector having titanium junctions whose sealing surfaces did not include an electrochemical corrosion-resistant material, the number of identified peptides decreased as the number of injections into the LC-MS system increased (e.g., as shown by the solid line marked with black circles). In a second experiment performed using a second connector having gold electrochemical corrosion-resistant material included in the sealing surfaces of the conductive junctions, the number of identified peptides decreased slightly as the number of injections into the LC-MS system increased (e.g., as shown by the dash-dotted line marked with white triangles). However, the number of peptides identified in the second experiment, performed with the second connector, did not decrease to the same extent as the number of peptides identified in the first experiment, performed with the first connector, which is likely due to the gold electrochemical corrosion-resistant material contained in the sealing surface of the second connector. Additionally, in the third experiment, performed with a third connector having a 904L stainless steel electrochemical corrosion-resistant material contained in the sealing surface of the conductive joint, the number of identified peptides only decreased slightly as the number of injections introduced into the LC-MS system increased (e.g., the third experiment ended at injection 300, as indicated by the dashed line marked with an "x").

[0060] The reduced decrease in the number of peptides identified using the second and third connectors with electrochemically corrosion-resistant materials is believed to further indicate that the electrochemically corrosion-resistant materials included in the sealing surfaces of the connectors reduce and / or eliminate corrosion of the joints and, therefore, reduce and / or eliminate emitter degradation over time. Thus, connectors including electrochemically corrosion-resistant materials on the first and second sealing surfaces of the conductive joints reduce and / or prevent connector corrosion and emitter degradation. Such reduction and / or prevention of connector corrosion may further reduce and / or prevent a decrease in sensitivity, efficiency, stability, and accuracy of the ESI method of an LC-MS system including electrochemically corrosion-resistant materials (e.g., by reducing and / or preventing contamination of the mobile phase with electrochemical products, broadening of chromatographic peaks, and / or a reduction in ion identification in the mass spectrum).

[0061] FIG. 9 shows a cross-sectional view of another illustrative implementation of an electrochemically resistant connector 208 .

[0062] Figure 9 is the same as Figure 6B, except that in Figure 9, the junction 602 is made from an electrochemical corrosion resistant material. Thus, at least the first sealing surface 612-1 and the second sealing surface 612-2 include an electrochemical corrosion resistant material to reduce and / or prevent corrosion of the junction 602 and / or degradation of the emitter 302.

[0063] In some examples, the junction 602 further includes a sacrificial electrode (not shown in FIG. 9 ) configured to interface with the mobile phase and to corrode preferentially relative to the electrochemically corrosion-resistant material of the first sealing surface 612-1 and the second sealing surface 612-2. For example, the sacrificial electrode can include a material having a standard reduction potential lower than that of the electrochemically corrosion-resistant material. In some examples, the sacrificial electrode includes a structure (e.g., a wire, rod, bar, coating, surface, etc.) made of titanium (or other metal with a standard reduction potential lower than that of the electrochemically corrosion-resistant material, such as stainless steel) positioned within the connector 208 or within the junction 602 (e.g., within the first receptacle 606-1, the second receptacle 606-2, and / or within the through-hole 608) to interface with the mobile phase. Additionally or alternatively, when the joint 602 includes a first material (e.g., titanium) and a coating (e.g., coating 614) including a second material coated on the first material at the first sealing surface 612-1 and the second sealing surface 612-2, the sacrificial electrode may include the first material, and the second material may include an electrochemical corrosion-resistant material. Such a sacrificial electrode corrodes preferentially over the electrochemical corrosion-resistant material at the first sealing surface 612-1 and the second sealing surface 612-2, thus further reducing and / or preventing corrosion at the first sealing surface 612-1 and the second sealing surface 612-2.

[0064] Other suitable configurations of the sacrificial electrode may be used. For example, the sacrificial electrode may include conductive particles packed into the emitter near the tip of the emitter in a filled-tip emitter configuration. The conductive particles may be formed of or coated with a sacrificial material (e.g., a material having a standard reduction potential lower than the standard reduction potential of the sealing surface of the conductive joint). In other examples, the sacrificial electrode includes a sacrificial material coating on the inner surface of the emitter. In some examples, the electrochemical corrosion-resistant material at the sealing surface of the joint may be omitted by instead using a sacrificial electrode formed from a material having a standard reduction potential lower than the standard reduction potential of the conductive joint.

[0065] 10A and 10B show various cross-sectional views of connector 208 to depict an illustrative method of fabricating connector 208. The method includes forming a junction 602 configured to provide an electrospray voltage to a mobile phase when junction 602 is electrically connected to a power source. As shown in FIG. 10A , forming junction 602 includes forming a first receptacle 606-1 at a proximal end of connector 208 to receive a distal end of a first conduit, forming a second receptacle 606-2 at the distal end of connector 208 to receive a proximal end of a second conduit, and forming a through-hole 608 extending from first receptacle 606-1 to second receptacle 606-2. The first receptacle 606-1 includes a first sealing surface 612-1 for interfacing with the mobile phase and fluidly sealing with the distal end of the first conduit. Similarly, the second receptacle 606-2 includes a second sealing surface 612-2 for interfacing with the mobile phase and fluidly sealing with the proximal end of the second conduit. The first sealing surface 612-1 and the second sealing surface 612-2 each include an electrochemical corrosion-resistant material. That is, the junction 602 in FIG. 10A is formed of an electrochemical corrosion-resistant material.

[0066] In another example, forming the joint 602 includes a multi-step process of forming the joint 602 from a first material (e.g., an electrically conductive material) and coating the first material with a second material comprising an electrochemical corrosion-resistant material at the first sealing surface 612-1 and the second sealing surface 612-2. For example, in a first step shown in FIG. 10A , the joint 602 is formed from a first material comprising an electrically conductive material. In a second step shown in FIG. 10B , a coating 614 comprising the second material is applied to the first sealing surface 612-1 and the second sealing surface 612-2. The coating 614 may be applied to the sealing surface 612 by any suitable method, such as, but not limited to, electroplating, sputter coating, chemical vapor deposition (CVD), electron beam evaporation, or thin film deposition. Other suitable methods for fabricating a connector 208 having first sealing surfaces 612-1 and second sealing surfaces 612-2 comprising an electrochemical corrosion-resistant material may be used. For example, coating 614 may additionally be applied to other surfaces of interface 602, such as the inner surfaces of through-holes 608 and / or other surfaces within receptacle 606 (eg, surfaces of dead volumes).

[0067] Various modifications can be made to the above example. For example, the ion source 106 can be configured to emit ions from the emitter 302 towards the entrance of an ion guide, ion optics, or any other ion manipulation device, such as an ion mobility separator. In other modifications, the above-described systems and methods can be used with other electrospray ionization techniques, such as paper spray ionization and polymer spray ionization.

[0068] While various illustrative examples have been described with reference to the accompanying drawings, those skilled in the art will recognize that various modifications and changes may be made thereto and additional examples may be implemented without departing from the scope of the following claims. For example, certain features of one embodiment described herein may be combined with or substituted for features of another embodiment described herein. Accordingly, the specification and drawings should be considered in an illustrative, and not a limiting, sense. Additionally, the drawings are not to scale, as various features (e.g., through-holes 608 and / or dead volumes) may be exaggerated to facilitate viewing and understanding of the concepts described herein.

[0069] The advantages and features of the present disclosure can be further illustrated by the following examples.

[0070] Example 1. A connector configured to fluidly couple a first conduit and a second conduit to allow a mobile phase for liquid chromatography to flow through the first conduit and the second conduit, the connector comprising an electrically conductive junction for providing an electrospray voltage to the mobile phase when the electrically conductive junction is electrically connected to a power source, the electrically conductive junction comprising a first receptacle for receiving a distal end of the first conduit, the first receptacle configured to interface with the mobile phase. a first receptacle for receiving a proximal end of a second conduit, the second receptacle having a first sealing surface that interfaces with a mobile phase and fluidly seals with the proximal end of the second conduit; a through hole extending from the first receptacle to the second receptacle, wherein the first sealing surface and the second sealing surface each comprise an electrochemical corrosion resistant material.

[0071] Example 2. The connector of Example 1, wherein the electrochemical corrosion-resistant material has a standard reduction potential greater than the reduction potential of a standard hydrogen electrode (SHE).

[0072] Example 3. The connector of example 1, wherein the electrochemical corrosion-resistant material has a standard reduction potential greater than the standard reduction potential of titanium.

[0073] Example 4. The connector of example 1, wherein the electrochemical corrosion resistant material comprises a precious metal.

[0074] Example 5. The connector of example 1, wherein the electrochemical corrosion resistant material comprises a metal alloy comprising greater than about twenty percent (20%) nickel by weight.

[0075] Example 6. The connector of example 1, wherein the electrochemical corrosion-resistant material comprises a metal alloy comprising less than about one weight percent (1%) iron.

[0076] Example 7. The connector of example 1, wherein the electrochemical corrosion resistant material comprises gold.

[0077] Example 8. The connector of Example 1, wherein the electrochemical corrosion resistant material comprises 904L stainless steel.

[0078] Example 9. The connector of example 1, wherein the electrically conductive joint comprises a first material and a second material comprising a coating on the first material at the first sealing surface and the second sealing surface, and the second material comprises an electrochemical corrosion resistant material.

[0079] Example 10. The connector of example 9, wherein the first material comprises titanium.

[0080] Example 11. The connector of example 9, wherein the first material is electrically conductive.

[0081] Example 12. The connector of example 9, wherein the conductive joint further comprises a second material on the first material on the inner surface of the through hole.

[0082] Example 13. The connector of example 9, wherein the coating is applied onto the first material at the first sealing surface and the second sealing surface by electroplating or sputter coating.

[0083] Example 14. The connector of example 1, wherein the conductive joint comprises an electrochemical corrosion resistant material.

[0084] Example 15. The connector of example 1, wherein the connector is a low dead volume or no dead volume connector.

[0085] Example 16. The connector of example 1, wherein the electrically conductive joint further comprises a sacrificial electrode configured to interface with the mobile phase and to corrode preferentially relative to the electrochemical corrosion-resistant material of the first sealing surface and the second sealing surface.

[0086] Example 17. The connector of example 16, wherein the sacrificial electrode comprises a metal having a lower standard reduction potential than the electrochemical corrosion-resistant material.

[0087] Example 18. The connector of example 16, wherein the conductive joint comprises a first material and a second material comprising a coating on the first material at the first sealing surface and the second sealing surface, the sacrificial electrode comprises the first material, and the second material comprises an electrochemical corrosion resistant material.

[0088] Example 19. A system for analyzing a sample by liquid chromatography mass spectrometry, the system comprising: a first conduit; a second conduit; an electrospray ionization (ESI) emitter; and a connector positioned between the first conduit and the second conduit and fluidly coupled to the first conduit and the second conduit to allow a mobile phase to flow through the first conduit and the second conduit to the ESI emitter, the connector including an electrically conductive junction, the electrically conductive junction being a first receptacle for receiving a distal end of the first conduit, the electrically conductive junction interfacing with the mobile phase and the distal end of the first conduit. a connector comprising: a first receptacle having a first sealing surface configured to fluidly seal with the proximal end of a second conduit; a second receptacle for receiving a proximal end of a second conduit, the second receptacle having a second sealing surface configured to interface with a mobile phase and to fluidly seal with the proximal end of the second conduit; a through hole extending from the first receptacle to the second receptacle, the first sealing surface and the second sealing surface each comprising an electrochemical corrosion resistant material; and a power source electrically connected to the conductive junction to provide an electrospray voltage to the mobile phase.

[0089] Example 20. The system of Example 19, further comprising a chromatography column comprising a stationary phase.

[0090] Example 21. The system of Example 20, wherein the chromatography column is positioned upstream of the connector such that an outlet of the chromatography column is fluidly coupled with the first conduit.

[0091] Example 22. The system of example 20, wherein the chromatography column is positioned downstream of the connector such that an inlet of the chromatography column is fluidly coupled with the second conduit.

[0092] Example 23. The system of example 19, wherein the electrochemical corrosion-resistant material has a standard reduction potential greater than a threshold standard reduction potential.

[0093] Example 24. The system of example 23, wherein the threshold standard reduction potential is the reduction potential of a standard hydrogen electrode (SHE).

[0094] Example 25. The system of example 23, wherein the threshold standard reduction potential is the standard reduction potential of titanium.

[0095] Example 26. The system of example 19, wherein the electrically conductive joint comprises a first material and a second material comprising a coating on the first material at the first sealing surface and the second sealing surface, and the second material comprises an electrochemical corrosion resistant material.

[0096] Example 27. The system of example 19, wherein the electrically conductive joint comprises an electrochemical corrosion resistant material.

[0097] Example 28. A method of making a connector configured to fluidly couple a first conduit and a second conduit to allow a mobile phase for liquid chromatography to flow through the first conduit and the second conduit, the method comprising forming a conductive junction configured to provide an electrospray voltage to the mobile phase when the conductive junction is electrically connected to a power source, the conductive junction comprising: a first receptacle at a proximal end of the connector for receiving a distal end of the first conduit; A method comprising: a first receptacle having a first sealing surface for interfacing with and fluidly sealing with the distal end of a first conduit; a second receptacle at a distal end of the connector for receiving a proximal end of a second conduit, the second receptacle having a second sealing surface for interfacing with a mobile phase and fluidly sealing with the proximal end of the second conduit; and a through hole extending from the first receptacle to the second receptacle, wherein the first sealing surface and the second sealing surface each comprise an electrochemical corrosion resistant material.

[0098] Example 29. The method of example 28, wherein the electrochemical corrosion-resistant material has a standard reduction potential greater than a threshold standard reduction potential.

[0099] Example 30. The method of example 28, wherein forming the conductive joint includes forming the conductive joint from a first material and coating a second material including an electrochemical corrosion resistant material on the first material at the first sealing surface and the second sealing surface.

[0100] Example 31. The method of example 30, wherein coating comprises electroplating or sputter coating the first sealing surface and the second sealing surface with an electrochemical corrosion resistant material.

[0101] Example 32. The method of example 28, wherein forming the conductive joint includes forming the conductive joint from an electrochemical corrosion resistant material.

Claims

1. 1. A connector configured to fluidly couple a first conduit and a second conduit to allow a mobile phase for liquid chromatography to flow through the first conduit and the second conduit, the connector comprising an electrically conductive junction for providing an electrospray voltage to the mobile phase when the electrically conductive junction is electrically connected to a power source, the electrically conductive junction comprising: a first receptacle for receiving a distal end of the first conduit, the first receptacle including a first sealing surface that interfaces with the mobile phase and fluidly seals with the distal end of the first conduit; a second receptacle for receiving a proximal end of the second conduit, the second receptacle including a second sealing surface that interfaces with the mobile phase and fluidly seals with the proximal end of the second conduit; a through hole extending from the first receptacle to the second receptacle; The connector, wherein the first sealing surface and the second sealing surface each comprise an electrochemical corrosion resistant material.

2. 10. The connector of claim 1, wherein the electrochemical corrosion resistant material has a standard reduction potential greater than the reduction potential of a standard hydrogen electrode (SHE).

3. 2. The connector of claim 1, wherein the electrochemical corrosion-resistant material has a standard reduction potential greater than the standard reduction potential of titanium.

4. The connector of claim 1 , wherein the electrochemical corrosion resistant material comprises a noble metal.

5. The connector of claim 1 , wherein the electrochemical corrosion resistant material comprises a metal alloy comprising greater than about twenty percent (20%) nickel by weight.

6. The connector of claim 1 , wherein the electrochemical corrosion resistant material comprises a metal alloy containing less than about one percent (1%) iron by weight.

7. The connector of claim 1 , wherein the electrochemical corrosion resistant material comprises gold.

8. The connector of claim 1 , wherein the electrochemical corrosion resistant material comprises 904L stainless steel.

9. 2. The connector of claim 1, wherein the electrically conductive joint comprises a first material and a second material comprising a coating on the first material at the first sealing surface and the second sealing surface, the second material comprising the electrochemical corrosion resistant material.

10. The connector of claim 9 , wherein the first material comprises titanium.

11. 10. The connector of claim 9, wherein the conductive joint further comprises the second material on the first material on the inner surface of the through hole.

12. The connector of claim 1 , wherein the electrically conductive joint is formed from the electrochemical corrosion resistant material.

13. 10. The connector of claim 1, wherein the conductive joint further comprises a sacrificial electrode configured to interface with the mobile phase and to corrode preferentially relative to the electrochemical corrosion-resistant material of the first sealing surface and the second sealing surface.

14. 14. The connector of claim 13, wherein the sacrificial electrode comprises a metal having a lower standard reduction potential than the electrochemical corrosion-resistant material.

15. 14. The connector of claim 13, wherein the conductive joint comprises a first material and a second material comprising a coating on the first material at the first sealing surface and the second sealing surface, the sacrificial electrode comprises the first material, and the second material comprises the electrochemical corrosion resistant material.

16. 1. A system for analyzing a sample by liquid chromatography-mass spectrometry, said system comprising: a first conduit; a second conduit; and an electrospray ionization (ESI) emitter; a connector positioned between the first conduit and the second conduit and fluidly coupled to the first conduit and the second conduit to allow a mobile phase to flow through the first conduit and the second conduit to the ESI emitter, the connector comprising a conductive junction, the conductive junction comprising: a first receptacle for receiving a distal end of the first conduit, the first receptacle including a first sealing surface configured to interface with the mobile phase and to fluidly seal with the distal end of the first conduit; a second receptacle for receiving a proximal end of the second conduit, the second receptacle including a second sealing surface configured to interface with the mobile phase and to fluidly seal with the proximal end of the second conduit; a through hole extending from the first receptacle to the second receptacle; a connector, wherein the first sealing surface and the second sealing surface each comprise an electrochemical corrosion resistant material; a power supply electrically connected to the conductive junction to provide an electrospray voltage to the mobile phase.

17. 17. The system of claim 16, further comprising a chromatography column comprising a stationary phase.

18. 18. The system of claim 17, wherein the chromatography column is positioned upstream of the connector such that an outlet of the chromatography column is fluidly coupled with the first conduit.

19. 18. The system of claim 17, wherein the chromatography column is positioned downstream of the connector such that an inlet of the chromatography column is fluidly coupled with the second conduit.

20. 1. A method of making a connector configured to fluidly couple a first conduit and a second conduit to allow a mobile phase for liquid chromatography to flow through the first conduit and the second conduit, the method comprising: forming a conductive junction configured to provide an electrospray voltage to the mobile phase when the conductive junction is electrically connected to a power source, the conductive junction comprising: a first receptacle at a proximal end of the connector for receiving a distal end of the first conduit, the first receptacle including a first sealing surface for interfacing with the mobile phase and fluidly sealing with the distal end of the first conduit; a second receptacle at a distal end of the connector for receiving a proximal end of the second conduit, the second receptacle including a second sealing surface for interfacing with the mobile phase and fluidly sealing with the proximal end of the second conduit; a through hole extending from the first receptacle to the second receptacle; The method, wherein the first sealing surface and the second sealing surface each comprise a galvanic corrosion resistant material.

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