Electrochemical corrosion resistant connector for liquid chromatography system

Abstract

The invention relates to an electrochemical corrosion resistant connector for a liquid chromatography system. A connector is configured to fluidly couple a first conduit and a second conduit to enable a mobile phase for liquid chromatography to flow through the first conduit and the second conduit. The connector includes a conductive contact for providing an electrospray voltage to the mobile phase when the conductive contact is electrically connected to a power source. The conductive tab includes: a first receiving portion having a first sealing surface interfacing with the flow and fluidly sealed with the distal end of the first catheter; a second receiving portion having a second sealing surface interfacing with the flow and fluidly sealed with the proximal end of the second conduit; and a through hole extending from the first receiving portion to the second receiving portion. The first sealing surface and the second sealing surface each comprise an electrochemically corrosion resistant material.

Description

Background Technology

[0001] A mass spectrometer is an instrument used to detect, identify, and / or quantify molecules based on their mass-to-charge ratio (m / z). A mass spectrometer typically includes an ion source for generating ions from components included in a sample, a mass analyzer for separating 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 ion among the detected ions, varying with m / z. The m / z of 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 in front of the mass analyzer inlet. A high voltage is applied to the liquid sample to generate an electrospray, thus forming analyte ions. Subsequently, the analyte ions entering the mass analyzer inlet are analyzed by mass spectrometry to generate a mass spectrum of the analyte ions.

[0003] In some cases, components of a sample are separated before ionization and introduction into the mass spectrometer, such as by liquid chromatography (LC). For example, analytes (e.g., peptides) are differentially retained on an LC column, and the LC system can separate the analytes within the sample over time. Then, as the analytes elute from the LC system over time, the mass spectrometer acquires a series of mass spectra. LC reduces the ionization suppression and spectral complexity that would result from directly injecting complex samples into the mass spectrometer. Therefore, by means of LC, the elution of analytes unfolds over time before introduction into the mass spectrometer. The mass spectra acquired by the mass spectrometer can be used to detect, identify, and / or quantify analytes in a sample.

[0004] An LC system typically includes a column and a pump for separating components in a sample. The column includes a stationary phase, such as a particulate material (e.g., an adsorbent, gel, etc.), and the pump delivers a mobile phase, such as a solvent (e.g., water, methanol, acetonitrile, etc.), through the column. The column outlet is fluidly connected to the ESI emitter of the mass spectrometer.

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

[0006] The following description presents a simplified overview of one or more aspects of the methods and systems described herein to provide a basic understanding of such aspects. This invention is not a comprehensive overview of all aspects covered, and is neither intended to identify key or decisive elements of all aspects nor to define the scope of any or all aspects. Its sole purpose is to present, in a simplified form, some concepts of one or more aspects of the methods and systems described herein as a prelude to the more detailed description presented below.

[0007] In some exemplary examples, a connector is configured to fluidly connect a first conduit and a second conduit to allow a mobile phase for liquid chromatography to flow through the first and second conduits. The connector includes a conductive joint for providing an electrospray voltage to the mobile phase when the conductive joint is electrically connected to a power source. The conductive joint includes: a first receiving portion for receiving a distal end of the first conduit, the first receiving portion including a first sealing surface that intersects with the mobile phase and fluidly seals the distal end of the first conduit; a second receiving portion for receiving a proximal end of the second conduit, the second receiving portion including a second sealing surface that intersects with the mobile phase and fluidly seals the proximal end of the second conduit; and a through-hole extending from the first receiving portion to the second receiving portion; wherein the first sealing surface and the second sealing surface each comprise an electrochemically resistant material.

[0008] In some exemplary 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 and fluidly connected to the first and second conduits such that a mobile phase can flow through the first and second conduits to the ESI emitter. The connector includes a conductive joint comprising: a first receiving portion for receiving a distal end of the first conduit, the first receiving portion including a first sealing surface; and the second conduit... A sealing surface is configured to interact with the flow phase and fluid-tighten the distal end of the first conduit; a second receiving portion for receiving the proximal end of the second conduit, the second receiving portion including a second sealing surface configured to interact with the flow phase and fluid-tighten the proximal end of the second conduit; and a through-hole extending from the first receiving portion to the second receiving portion; wherein the first sealing surface and the second sealing surface each comprise an electrochemically resistant material; and a power source electrically connected to the conductive connector to provide an electrospray voltage to the flow phase.

[0009] In some exemplary examples, a method of manufacturing a connector configured to fluidly connect a first conduit and a second conduit to allow a mobile phase for liquid chromatography to flow through the first and second conduits includes: forming a conductive joint configured to provide an electrospray voltage to the mobile phase when the conductive joint is electrically connected to a power source, the conductive joint including: a first receiving portion located at a proximal end of the connector for receiving a distal end of the first conduit, the first receiving portion including a first sealing surface for interacting with the mobile phase and fluidly sealing the distal end of the first conduit; a second receiving portion located at a distal end of the connector for receiving a proximal end of the second conduit, the second receiving portion including a second sealing surface for interacting with the mobile phase and fluidly sealing the proximal end of the second conduit; and a through-hole extending from the first receiving portion to the second receiving portion; wherein the first sealing surface and the second sealing surface each comprise an electrochemically resistant material. Attached Figure Description

[0010] The accompanying drawings illustrate various examples and are part of the specification. The examples shown are merely illustrative and do not limit the scope of this disclosure. Throughout the drawings, the same or similar reference numerals denote the same or similar elements.

[0011] Figure 1 The functional components of an exemplary liquid chromatography-mass spectrometry (LC-MS) system are shown.

[0012] Figure 2 It shows that it includes Figure 1 The functional components of an exemplary liquid chromatography (LC) system in an LC-MS system.

[0013] Figure 3 It shows that it includes Figure 1 Functional diagram of an exemplary ion source in an LC-MS system.

[0014] Figure 4A The drawing is shown via LC-MS (e.g., via...). Figure 1 An illustrative graph showing how the amount of peptides recognized by a specific emitter varies with the number of injections into the LC-MS system using that specific emitter.

[0015] Figure 4B The drawing is shown via LC-MS (e.g., via...). Figure 1 An illustrative graph showing how the peak width of a chromatographic peak obtained using a specific emitter varies with the number of times the specific emitter is injected into the LC-MS system.

[0016] Figure 5AThe drawing is shown via LC-MS (e.g., via...). Figure 1 Another example of an LC-MS system is the amount of peptides recognized by a specific emitter that varies with the number of times the specific emitter is injected into the LC-MS system.

[0017] Figure 5B The drawing can be performed via LC-MS (e.g., via...). Figure 1 An illustrative graph showing how the resistance of the mobile phase obtained using a specific emitter varies with the number of times the specific emitter is injected into the LC-MS system.

[0018] Figure 6A A perspective view of an exemplary electrochemically resistant connector for an LC-MS system is shown.

[0019] Figure 6B It shows along Figure 6A The dotted line marked VIB in the middle is the cut-off point. Figure 6A A cross-sectional view of the connector.

[0020] Figure 6C It shows Figure 6A A view of the proximal end of the connector.

[0021] Figure 6D It shows Figure 6A A view of the distal end of the connector.

[0022] Figure 7A The connection to the chromatographic column and electrospray ionization emitter is shown. Figure 6A An illustrative construction of the connector.

[0023] Figure 7B It shows Figure 7A A cross-sectional view of the structure.

[0024] Figure 8A The drawing is shown via LC-MS (e.g., via including...). Figure 6A An illustrative graph showing how the peak width of a chromatographic peak obtained using a specific emitter varies with the number of injections into the LC-MS system using that specific emitter.

[0025] Figure 8B The diagram illustrates plotting the starting voltage of a specific transmitter as it is injected into an LC-MS system (e.g., including...). Figure 6A An illustrative curve showing the variation in the number of times the connector in the LC-MS system changes.

[0026] Figure 9 A cross-sectional view of another exemplary electrochemically resistant connector for an LC-MS system is shown.

[0027] Figure 10A A cross-sectional view of an electrochemically resistant connector for an LC-MS system, comprising a first material, is shown.

[0028] Figure 10B It shows Figure 10A A cross-sectional view of a connector, the connector comprising a second material coated on a first material at a first sealing surface and a second sealing surface. Detailed Implementation

[0029] As described herein, the connector is configured to fluidly connect components of an LC-MS system and, when the ESI emitter is not conductive, provide a liquid-metal interface for applying an electrospray voltage to the mobile phase. In some exemplary examples, the connector includes a conductive portion that interacts with the mobile phase to provide an electrospray voltage to the mobile phase when the conductive portion is electrically connected to a power source. The conductive portion includes a first receiving portion for receiving the distal end of a first conduit (e.g., a conduit included in or fluidly coupled to a column); a second receiving portion for receiving the 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 receiving portion to the second receiving portion to allow mobile phase flow through therethrough. The conductive portion incorporates an electrochemically resistant material that reduces or eliminates electrochemical corrosion at the sealing surface compared to conventional connectors used in LC-MS, and thus contributes to extending the usable life of the ESI emitter and improving the sensitivity and resolution of ESI-based LC-MS methods.

[0030] The systems and methods described herein can be implemented in conjunction with liquid chromatography-mass spectrometry (LC-MS) systems. Figure 1 The functional components of an exemplary LC-MS system 100 are shown. As illustrated, 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 the components to the mass spectrometer 104 for mass analysis. In some examples, the LC system 102 may also detect the relative abundance of the separated components, such as by generating chromatograms representing the components within the sample. References below... Figure 2 The exemplary LC system 102 is described in more detail.

[0031] The mass spectrometer 104 includes an ion source 106, a mass analyzer 108, and a controller 110. The mass spectrometer 104 may also include any additional or alternative components (not shown) that may be suitable for a particular implementation (e.g., ion optics, filters, autosamplers, etc.).

[0032] Ion source 106 is configured to generate an ion stream 112 from the sample via electrospray ionization (ESI) and deliver the ions to mass analyzer 108. See below for reference. Figure 3 A more detailed description of the illustrative ion source.

[0033] Mass analyzer 108 is configured to receive ion stream 112 and separate ions based on the m / z of each ion in the stream. Mass analyzer 108 can 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 orbital trap mass analyzer, a Kingdon trap, an electrostatic linear ion trap, etc.), a Fourier transform ion cyclotron resonance (FT-ICR) mass analyzer, a sector mass analyzer, etc.

[0034] An ion detector (not shown) is configured to detect ions at each of a variety of different m / z and responsively generate an electrical signal representing the ion intensity. The electrical signal is sent to a controller 110 for processing, such as constructing a mass spectrum of the sample. For example, a mass analyzer 108 may emit an emission beam of separated ions to an ion detector configured to detect ions in the emission beam and generate or provide data that the controller 110 can use to construct a mass spectrum of the sample. The ion detector can be implemented by any suitable detection device, including but not limited to electron multipliers, Faraday cups, etc.

[0035] Controller 110 is communicatively coupled to LC-MS system 100 and configured to control the operation of the LC-MS system. For example, controller 110 may be configured to control the operation of various hardware components included in LC system 102, ion source 106, mass analyzer 108, and / or detector. For illustration, controller 110 may be configured to control the amount of mobile phase pumped through LC system 102, control the high voltage applied to the connector of LC system 102, control the accumulation time of mass analyzer 108, control the oscillating voltage power supply and / or DC power supply to supply RF voltage and / or DC voltage to mass analyzer 108, adjust the values ​​of RF voltage and DC voltage to select the effective m / z (including the mass tolerance window) for analysis, and adjust the sensitivity of the ion detector (e.g., by adjusting the detector gain).

[0036] Unless the context otherwise specifies or indicates, the terms “a” and “the” mean “one or more”. For example, “a molecule” should be interpreted as meaning “one or more molecules”.

[0037] As used herein, “approximately” and “substantially” are understood by those skilled in the art and differ to some extent depending on the context in which they are used. If the use of terms is unclear to those skilled in the art given the context in which they are used, then “approximately” and “substantially” mean less than or equal to 10% of a particular value.

[0038] Figure 2 The functional components of an exemplary embodiment 200 of the LC system 102 are shown. As shown, the LC system 102 includes a mobile phase source 202, a pump 204, a chromatographic column 206 (“column 206”), and a connector 208. Figure 2 This is merely an example, as the LC system 102 may have other suitable configurations. The LC system 102 may also include... Figure 2 Additional or alternative components not shown may serve a particular implementation (e.g., detector, degassing unit, syringe, column box, etc.).

[0039] Mobile phase source 202 provides a mobile phase that receives the injection of sample 210 and flows through column 206 and connector 208 to transport sample 210 to ion source 106 of mass spectrometer 104. The mobile phase may include solvents such as water, methanol, acetonitrile, etc. In some examples, the mobile phase flows through 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). In nanospray ionization (NSI), the mobile phase can flow through LC system 102 at nanoscale flow rates ranging from about 10 nanoliters (nL) per minute to 50 nanoliters per minute (10 nL / min to 50 nL / min) to about 1000 nL / min to 1500 nL / min. Sample 210 may include, for example, chemical components (e.g., molecules, ions, etc.) and / or biological components (e.g., metabolites, proteins, lipids, etc.) for detection and analysis by LC-MS system 100.

[0040] Pump 204 is fluidly coupled to mobile phase source 202 and configured to pump the mobile phase through column 206 and connector 208 to ion source 106. For illustration, pump 204 is configured to deliver the mobile phase to column 206 and / or connector 208 at a stable (e.g., substantially constant) flow rate. In some examples, pump 204 includes at least one pair of reciprocating pistons, such that a first piston delivers the flow while a second piston draws in the mobile phase at a stable flow rate. The pump can be implemented using any suitable pumping device, including but not limited to reciprocating pumps, syringe pumps, binary pumps, constant-pressure pumps, quaternary pumps, etc. In some examples, pump 204 may be communicatively coupled to controller 110, such that controller 110 is configured to control the flow rate of the mobile phase delivered by pump 204. Additionally, the flow rate of pump 204 may be programmable, such as through a user interface of controller 110.

[0041] Column 206 is configured to receive a mobile phase delivered by pump 204. Column 206 includes a stationary phase, such as a particulate material (e.g., adsorbent, gel, porous solid such as glass, silica, alumina, etc.). In some examples, the stationary phase is bound or adsorbed onto the inner surface of the openings of column 206 and / or is filled within the openings of column 206. The stationary phase is configured to interact differentially with the components of sample 210 in the mobile phase to separate the components of sample 210 based on, for example, their size, their affinity for the stationary phase, their polarity, and / or their hydrophobicity.

[0042] A mobile phase flows from column 206 to ion source 106 to ionize the analyte within the mobile phase and guide the ions into mass analyzer 108. In the example described herein, ion source 106 ionizes the analyte by electrospray ionization. Electrospray ionization is performed by pumping the mobile phase through the emitter of 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 is conductive (e.g., stainless steel) or non-conductive (e.g., glass). In the case of a conductive emitter, a high potential difference of approximately 1 kV to 5 kV is maintained between the emitter and the mass spectrometer inlet, acting as a counter electrode. In the case of a non-conductive emitter, a liquid-metal connector is located upstream of the emitter tip for applying the electrospray voltage to the mobile phase, which is transmitted to the emitter tip via the conductivity of the mobile phase.

[0043] Connector 208 is configured to fluidly connect components of the LC-MS system 100 and, when the emitter is non-conductive, provide a liquid-metal interface for applying an electrospray voltage to the mobile phase. As shown, connector 208 is located between post 206 and ion source 106 to fluidly connect the LC system 102 to ion source 106. However, in other examples ( Figure 2(Not shown in the image) Connector 208 may be located elsewhere within LC system 102 and for fluid connection to other components of LC-MS system 100. For example, connector 208 may be located upstream of column 206 such that connector 208 fluidly connects pump 204 to column 206. Additionally or alternatively, column 206 and / or connector 208 may be located within ion source 106.

[0044] As will be described in more detail below, connector 208 includes a conductive connector having a first receiving portion for receiving a first conduit (e.g., included in or fluidly coupled to post 206); a second receiving portion for receiving a second conduit (e.g., included in or fluidly coupled to ion source 106); and a through-hole extending from the first receiving portion to the second receiving portion to allow flow of the mobile phase through therethrough. The conductive connector may be integral with and / or inserted into connector 208.

[0045] The conductive connector 208 intersects with the mobile phase and includes a conductive material, such that the connector is configured to provide an electrospray voltage (e.g., approximately 2 kV to 6 kV for ESI, or approximately 0.7 kV to 3.5 kV for NSI) to the mobile phase when the conductive connector is electrically coupled to the power source 212. The conductive connector can be connected to the power source 212 via a high-voltage line 214 (e.g., cable or other wiring or electrical connection). The electrospray voltage can be carried by the mobile phase to the ESI emitter of the ion source 106.

[0046] Figure 3 A functional diagram illustrating an exemplary embodiment 300 of the interface between the ion source 106 and the mass analyzer 108 is shown. Figure 3 This is merely an example, as the ion source 106 and mass analyzer 108 may have other suitable configurations. As shown, the ion source 106 includes an ESI emitter 302. The ion source 106 may also include... Figure 3 Additional or alternative components, not shown, that may serve a particular implementation, such as positioning systems, voltage sources, housings (e.g., components that house the ion source 106 and / or are attached to the mass analyzer 108), cameras, adapters, locks, mounting components, gas supply lines, etc.

[0047] The emitter 302 may be implemented using 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 polyimide or other polymer coating. In some examples, the emitter 302 is configured for low flow rates of NSI (e.g., about 10 nL / min to 50 nL / min to up to about 1000 nL / min to 1500 nL / min). In other examples, the emitter 302 is configured for capillary flow rates (e.g., about 1 μL / min to up to about 10 μL / min to 20 μL / min), microflow rates (e.g., about 10 μL / min to up to about 100 μL / min), or conventional ESI analysis flow rates (e.g., greater than about 50 μL / min). Transmitter 302 may be included in a transmitter housing, which may include, but is not limited to, a mounting unit for holding transmitter 302, an adapter for connecting or integrating transmitter 302 with LC system 102, onboard non-volatile memory (which may store location data and / or other data that can be used to locate transmitter 302), and / or any other suitable components. In some examples where the transmitter housing includes onboard memory, the transmitter housing may be communicatively coupled to controller 110, such as by means of a wired or wireless connection.

[0048] The LC system 102 provides a mobile phase flowing through the emitter 302. An electrospray voltage is applied (e.g., by means of a high-voltage line 214) to a metal connector 208 that intersects 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. As ions are emitted from the tip 304 of the emitter 302, the electric field induces ion migration in the mobile phase, causing electrohydrodynamic disintegration of the mobile phase, generation of charged droplets, and formation of a spray plume 306 traveling toward the inlet 308 of the mass analyzer 108. As the spray plume 306 travels toward the inlet 308, solvent evaporates from the charged droplets, causing a gradual increase in the charge intensity on the surface of the droplets until the droplets break apart into one or more charged phase ions. Then, charged phase ions are introduced into inlet 308 of mass analyzer 108 by applying an electric field, a vacuum, and, if present, a sheath gas at emitter 302.

[0049] In some examples, the emitter 302 is inserted into the nozzle 310, and a sheath gas, such as nitrogen (N2), 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 orientation of the spray plume 306 and reducing mass stratification. The sheath gas flow rate can be adjusted to achieve the desired position and shape of the spray plume 306. The sheath gas can also lower the surface tension barrier to initiate the formation of the spray plume 306. In another example, a heated auxiliary gas can be used to aid in the desolvation of charged droplets in the spray plume 306. However, at low flow rates (e.g., nanoflows), good sensitivity can be obtained without a sheath gas and / or auxiliary gas.

[0050] In some examples, the positioning system 312 is configured to hold the tip 302 of the transmitter 304 at a controlled distance (e.g., about 0.1 cm to 3 cm) from the inlet 308 of the mass analyzer 108. Additionally, as... Figure 3 As shown, emitter 302 is angled relative to the longitudinal axis of inlet 308. Any suitable angle can be used (e.g., 45°, 30°, 22.5°, 15°, etc.). In other examples, emitter 302 is not angled relative to the longitudinal axis of inlet 308, but is positioned such that the longitudinal axis of emitter 302 is substantially parallel to the longitudinal axis of inlet 308. For illustrative purposes only, inlet 308 is shown adjacent to mass analyzer 108. It will be appreciated that various other components can be positioned between inlet 308 and mass analyzer 108, such as, but not limited to, ion optics, ion guides, ion traps, ion mobility separators, filters, and / or collision chambers. Inlet 308 can have any suitable configuration, such as an orifice or capillary (e.g., an ion transfer tube (ITT), such as a circular orifice ITT, or a high-capacity transfer tube (HCTT), such as a mailbox inlet). In an alternative example, inlet 308 is a field asymmetric ion mobility spectrometry (FAIMS) inlet aperture, wherein the FAIMS electrode is positioned directly in front of the inlet of the mass analyzer. When emitter 302 is mounted on positioning system 312, positioning system 312 can automatically adjust the position of emitter 302 relative to inlet 308 (e.g., the position of tip 304).

[0051] The mass analyzer 108 receives analyte ions from the spray plume 306 entering the inlet 308 and performs mass analysis on the analyte ions. As explained above, the controller 110 can process the received signal and construct a mass spectrum of the ions introduced into the inlet 308 based on the signal detected by the ion detector in the mass analyzer 108.

[0052] As mentioned above, the performance of transmitter 302 decreases with increased use. LC-MS experiments were conducted to evaluate the performance change with transmitter aging, and the results are shown in... Figure 4A and Figure 4B The curve is shown in the graph. The experiment consisted of a sequence of 500 injections of 1 μg HeLa cell digestion solution. Additionally, the sequence included a blank run every 5 injections, resulting in a total of 575 injections. Therefore, the blank and performance runs were counted, and the transmitter underwent approximately 20% additional injections, which is not reflected in the curve. Figure 4A and Figure 4B The curves shown are illustrated. In the LC-MS experiments, a 200 ng HeLa loading was used. A connector, including a titanium joint, fluidly connects the emitter to the LC column. For each sample injection, an electrospray voltage is applied to the mobile phase via the titanium joint in the connector to form a spray plume of ions for mass analysis (e.g., identifying the number of peptides within the sample). Figure 4A The drawing is shown via LC-MS (e.g., via...). Figure 1 The LC-MS system uses an illustrative curve (Figure 400) showing the variation in the amount of peptide recognized by the emitter with the number of injections into the LC-MS system. For example... Figure 4A As shown, the number of peptides reliably identified by LC-MS analysis decreased with increasing number of injections into the LC-MS system, which is believed to be due to emitter degradation with increasing number of injections.

[0053] Figure 4B The drawing was shown Figure 4A LC-MS analysis uses an illustrative curve (Figure 402) showing the change in peak width of chromatographic peaks acquired using the transmitter as a function of the number of injections into the LC-MS system. Peak width is measured at half-maximum width (FWHM). As shown, the peak width increases with the number of injections into the LC-MS system, which is considered to be due to transmitter degradation. This broadening of the peak may degrade the performance of the LC-MS system and make it difficult to distinguish peptides within the sample.

[0054] The inventors aimed to identify the root cause of performance degradation and design emitter devices with extended lifetimes. Essentially, ESI is a dual-electrode controlled-current electrochemical cell. For a conductive emitter, the emitter is the working electrode, while the mass spectrometer inlet is the counter electrode. The emitter also serves as a current-controlled source. The rate at which the ion source generates charged droplets defines the average current flowing within the cell. In positive mode, oxidation reactions occur in the ESI emitter. Due to the current generated from the source, an interfacial potential is generated at the working electrode. The current density at the working electrode affects the interfacial potential, which ultimately determines the possible reactions in the system and the rates at which these reactions occur. Differences in working electrode materials become most pronounced at low current densities. For stainless steel emitters, low anolyte currents drive reactions involving iron corrosion, while at higher current densities, the interfacial potential increases to oxidize other substances in the system, including the solvent. Therefore, the physical location of the electrochemical reactions and electrode materials can influence mass spectrometry. For example, in a traction-type static nanospray emitter where electrochemistry occurs within the same physical space as the sample, mass spectrometry can often become time-correlated as the enrichment of electrochemical products occurs. Alternatively, anodic corrosion of zinc and stainless steel emitters has been shown to produce Zn in mass spectrometry. 2+ and Fe 2+ Ions. However, determining the exact nature and extent of these electrochemical reactions is often a challenging problem.

[0055] The inventor noted that, in reference Figure 4A and Figure 4B In the described experiment, deposits formed at the transmitter tip with increased use. Therefore, the inventors conducted LC-MS experiments to evaluate whether cleaning the transmitter tip would improve transmitter performance and extend transmitter life, and the results are shown in... Figure 5A and Figure 5B The curve is shown in the figure. The experiment consisted of a sequence of 200 injections of 1 μg HeLa cell digestion solution. Additionally, the sequence included a blank run every 5 injections. Therefore, blank runs and performance runs were counted, with the transmitter experiencing approximately 20% additional injections, which was not reflected in the curve. Figure 5A and Figure 5B The curves shown are illustrated. In the LC-MS experiment, a 200 ng HeLa loading was used.

[0056] Figure 5AAn exemplary plot 500 is shown, plotting the amount of peptides identified by LC-MS using a specific transmitter as a function of the number of injections into the LC-MS system with that specific transmitter. As shown, the number of peptides identified by the LC-MS system decreases with increasing number of injections into the LC-MS system, which is considered to be due to transmitter degradation. Based on visual observation of the transmitter, the inventors believed that the degradation of transmitter performance was likely due to deposits (e.g., analyte ions, solvent ions, environmental ions, electrochemical products, etc.) accumulated on the transmitter. Therefore, the transmitter was cleaned to remove the deposits. Cleaning involved ultrasonic cleaning of the transmitter for approximately 60 minutes and immersing the transmitter overnight in a sodium hydroxide solution (e.g., a solution containing 12 moles of sodium hydroxide per liter (12M NaOH)). After cleaning the transmitter, the sample was re-injected into the LC-MS system in small amounts using the same transmitter. However, after the transmitter cleaning, the number of peptides identified by the LC-MS system did not increase significantly, indicating that the performance degradation was not due to deposits accumulated on the exterior of the transmitter.

[0057] Figure 5B The drawing was shown Figure 5A Schematic plot 502 illustrates the change in resistance of the mobile phase obtained using the same emitter as the number of times the emitter is injected into the LC-MS system. As shown, the resistance of the mobile phase (e.g., approximately 99% water containing 0.1% formic acid) decreases with increasing number of injections into the LC-MS system, which is considered to be due to emitter degradation. Similar to the number of peptides identified by the LC-MS system, the resistance of the mobile phase within the LC-MS system did not increase significantly after cleaning the emitter, further indicating that emitter degradation is not due to deposits accumulated on the exterior of the emitter.

[0058] Because cleaning the emitter to remove deposits accumulated on its exterior failed to significantly improve emitter performance, and based on mobile phase resistance measurements, the inventors investigated whether the performance degradation with emitter aging was associated with electrochemical reactions occurring within the flow path of the mobile phase. The inventors have discovered that, for non-conductive emitter configurations, electrochemical reactions may occur upstream of the emitter at the liquid-metal interface of the titanium connector in a connector included in an LC-MS system. Conventional connectors use titanium as the conductive connector because titanium can be reproducibly machined with small through-holes (approximately 50 μm in diameter and approximately 0.5 mm in length) to allow fluid flow through the connector. The titanium connector interacts with the mobile phase to provide an electrospray voltage to the mobile phase. The electric field generated by the electrospray voltage enriches positively charged ions near the liquid meniscus of the mobile phase. When the Coulomb force is sufficient to overcome the surface tension of the mobile phase, positively charged droplets form. Due to the loss of positive charge via droplet formation, electron transfer reactions involving mobile phase ions (e.g., electrochemical reactions such as oxidation) occur at the liquid-metal interface of the connector. Such electron transfer reactions electrochemically corrode the liquid-metal interface of the highly electronegative titanium connector, thus forming or increasing dead volume within the connector, adding contaminants to the mobile phase, and forming deposits on the inner surface of the transmitter. All of these contribute to transmitter degradation, reduce transmitter performance over time, and / or contaminate the mass spectrometer generated by the mass spectrometer.

[0059] To prevent these problems, the liquid-metal interface of the connector included in the LC-MS system may comprise an electrochemically corrosion-resistant material. In some exemplary examples, the connector is configured to fluidly connect a first conduit (e.g., included in or fluidly coupled to a column) and a second conduit (e.g., included in or fluidly coupled to an ESI emitter) such that the mobile phase for liquid chromatography can flow through the first and second conduits. The connector includes a conductive connector for providing an electrospray voltage to the mobile phase when the conductive connector is electrically connected to a power source. The conductive connector includes a first receiving portion for receiving a distal end of the first conduit; a second receiving portion for receiving a proximal end of the second conduit; and a through-hole extending from the first receiving portion to the second receiving portion. The conductive connector comprises an electrochemically corrosion-resistant material.

[0060] The systems, devices, and apparatuses described herein offer various benefits that may include one or more advantages over conventional LC-MS systems and connectors. For example, the systems, devices, and apparatuses described herein include electrochemically resistant materials at the conductive contacts of the connectors. Additionally, the systems, devices, and apparatuses described herein can be configured to reduce and / or prevent electrochemical reactions at the conductive contacts to reduce and / or prevent connector corrosion and / or emitter degradation. Reducing and / or preventing connector corrosion and / or emitter degradation can further reduce and / or prevent a decrease in the sensitivity, efficiency, stability, and accuracy of the ESI method of the LC-MS system including the electrochemically resistant materials (e.g., by reducing and / or preventing mobile phase contamination by electrochemical products, peak broadening in chromatography, and / or reduced ion recognition in mass spectrometry).

[0061] Various illustrative examples will now be described in more detail with reference to the accompanying drawings. The systems, devices, and apparatuses described herein may provide one or more of the benefits described above, as well as various additional and / or alternative benefits that will become apparent herein.

[0062] Figures 6A to 6D Various views are shown of an exemplary embodiment of an electrochemically resistant connector 208 for an LC-MS system (e.g., LC-MS system 100). Figure 6A A perspective view of connector 208 is shown. Figure 6B It shows along Figure 6A A cross-sectional view of connector 208, taken by the dotted-dash line marked VIB. Figure 6C and Figure 6D Views of the proximal and distal ends of connector 208 are shown separately. 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 therefore can be connected in any orientation.

[0063] like Figures 6A to 6D As shown, connector 208 includes an outer sheath 600 and a conductive contact 602 extending within the outer sheath 600. Although the outer sheath 600 is shown as having an elongated cylindrical shape, other suitable shapes for the outer sheath 600 (e.g., cubic, prismatic, conical, etc.) may be used. In some examples, the outer sheath 600 includes a grip 604 having one or more flat surfaces configured to facilitate engagement of connector 208 with other components of the LC-MS system (e.g., one or more conduits included in the LC-MS system).

[0064] The connector 602 includes a first receiving portion 606-1 for receiving a first conduit (e.g., a conduit included in or fluidly connected to the column 206), a second receiving portion 606-2 for receiving a second conduit (e.g., a conduit included in or fluidly connected to the transmitter 302), and a through-hole 608 extending between the first receiving portion 606-1 and the second receiving portion 606-2 to allow flow phase to pass through therein. In the illustrated example, a portion of each receiving portion 606 is a conical shape that narrows toward the through-hole 608, which facilitates receiving and / or connecting conduits therein. However, the receiving portion 606 may include other suitable shapes (e.g., cylindrical, cubic, prismatic, etc.). For example, the receiving portion 606 may have a constant diameter such that the receiving portion 606 does not narrow toward the through-hole 608. In some examples, each receiving portion 606 includes a thread 610 to facilitate receiving and / or connecting conduits therein. Figure 6B As shown, connector 602 is integral with outer sheath 600. In other examples (not shown), connector 602 is different from outer sheath 600, but is installed or disposed within the outer sheath.

[0065] The connector 602 also includes a first sealing surface 612-1 within a first receiving portion 606-1 and a second sealing surface 612-2 within a second receiving portion 606-2. The first sealing surface 612-1 is configured to interact with the flow and to fluid-tightly seal the distal end of the first conduit. For example, the first sealing surface 612-1 extends inwardly within the first receiving portion 606-1 at the distal end 616, such that when the first conduit is positioned in the first receiving portion 606-1, the distal end of the first conduit is configured to abut or be positioned near the first sealing surface 612-1. Similarly, the second sealing surface 612-2 is configured to interact with the flow and to fluid-tightly seal the proximal end of the second conduit. For example, the second sealing surface 612-2 extends inward within the second receiving portion 606-2 at the proximal end 618 of the second receiving portion 606-2, such that when the second conduit is positioned in the second receiving portion 606-2, the proximal end of the second conduit is configured to be adjacent to or located near the second sealing surface 612-2.

[0066] Connector 602 includes a first conductive material (e.g., titanium) such that when connector 602 is electrically coupled to a power source, connector 602 is configured to provide an electrospray voltage to the mobile phase through the liquid-metal interface of connector 602 (e.g., at sealing surface 612 and / or in through-hole 608). Connector 602 also includes a second material at the first sealing surface 612-1 and the second sealing surface 612-2. The second material is an electrochemically resistant material, such that the second material is configured to reduce and / or prevent electrochemical reactions and / or electrochemical corrosion at connector 602 (e.g., at sealing surface 612). As shown, the second material is a coating 614 on the first material at the first sealing surface 612-1 and the second sealing surface 612-2. Coating 614 can be applied to sealing surface 612 by any suitable means (e.g., by electroplating, sputtering coating, chemical vapor deposition (CVD), electron beam vapor deposition, thin film deposition, etc.). Other suitable configurations for including an electrochemically resistant material in connector 602 can be used. For example, coating 614 may also be applied to additional surfaces of connector 602 (such as the inner surface of through-hole 608). Additionally or alternatively, connector 602 may be formed entirely of an electrochemically corrosion-resistant material, as will be described in more detail below.

[0067] Electrochemically resistant materials are conductive materials whose standard reduction potential is greater than the threshold standard reduction potential (e.g., more positive than the threshold standard reduction potential). The standard reduction potential of a substance indicates its tendency to be reduced. It 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 from the substance being measured. The standard reduction potential of a substance is measured at a temperature of 298 K, a pressure of 1 atm, 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 still other examples, the threshold standard reduction potential is -1.0 V, -0.5 V, -0.3 V, -0.25 V, -0.1 V, +0.1 V, +0.25 V, +0.5 V, +0.75 V, or +1.0 V.

[0068] In some examples, electrochemically resistant materials include noble metals. As used herein, noble metals include platinum group metals (ruthenium, rhodium, palladium, osmium, iridium, platinum), gold, silver, copper, rhenium, and mercury. 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, electrochemically resistant materials include cobalt or nickel, which have standard reduction potentials greater than -0.30. Additionally or alternatively, electrochemically resistant materials include stainless steel, such as 904L stainless steel. While 904L stainless steel is not completely corrosion resistant, it significantly reduces electrochemical corrosion compared to titanium. In some examples, the electrochemically resistant corrosion material includes a metal alloy comprising more than about 10% (10%) nickel, more than 15% (15%) nickel, more than 20% (20%) nickel, more than 25% (25%) nickel, or more than 30% (30%) nickel by mass. Additionally or alternatively, the electrochemically resistant corrosion material includes a metal alloy comprising less than about 5% (5%) iron, less than 3% (3%) iron, or less than 1% (1%) iron by mass. In some examples, the electrochemically resistant corrosion material includes a metal alloy comprising more than 20% (20%) nickel and less than 1% (1%) iron by mass.

[0069] Figure 7A and Figure 7B An exemplary configuration 700 of a connector 208 is shown, which is connected to a post 206 and a transmitter 302 via conduits 702 (e.g., conduits 702-1 and 702-2). As shown, the post 206 is connected to the proximal end of the first conduit 702-1 such that an opening 704 of the post 206 is fluidly connected to a first opening 706-1 extending through the first conduit 702-1 to allow flow of the mobile phase therethrough. The first conduit 702-1 extends from the post 206 to the connector 208 such that a distal end of the first conduit 702-1 is received within a first receiving portion 606-1 of the connector 208 to fluidly connect the first opening 706-1 of the first conduit 702-1 to a through-hole 608 to allow flow of the mobile phase therethrough. Furthermore, the distal end of the first conduit 702-1 is positioned at the first sealing surface 612-1 of the first receiving portion 606-1, such that the first sealing surface 612-1 fluidly seals with the proximal end of the first conduit 702-1 (to prevent leakage of the flowing phase from the connector 208) and exchanges with the flowing phase.

[0070] Similarly, the emitter 302 is connected to the distal end of the second conduit 702-2 such that the capillary 708 of the emitter 302 is fluidly connected to the second opening 706-2 extending through the second conduit 702-2 to allow the mobile phase to flow through it. The second conduit 702-2 extends from the emitter 302 to the connector 208 such that the proximal end of the second conduit 702-2 is received within the second receiving portion 606-2 of the connector 208 to fluidly connect the second opening 706-2 of the second conduit 702-2 to the through-hole 608 to allow the mobile phase to flow through it. Furthermore, the proximal end of the second conduit 702-2 is positioned at the second sealing surface 612-2 of the second receiving portion 606-2 such that the second sealing surface 612-2 fluidly seals with the distal end of the second conduit 702-2 (to prevent leakage of the mobile phase from the connector 208) and exchanges with the mobile phase. Therefore, connector 208 is configured to fluidly connect post 206 to transmitter 302 to allow the flow phase to flow from post 206 to transmitter 302.

[0071] Although Figure 7A and Figure 7B The example shown depicts a connector 208 positioned between post 206 and transmitter 302, but in other examples ( Figure 7A and Figure 7B In (not shown), connector 208 is positioned elsewhere within LC system 102 and is used for fluid connection to other components of LC-MS system 100. For example, connector 208 may be additionally or alternatively positioned upstream of column 206 such that connector 208 fluidly connects pump 204 to column 206.

[0072] In some examples, connector 208 is a dead volume-free (or zero dead volume (ZDV)) connector. For illustration, the distal end of the first conduit 702-1 may abut the first sealing surface 612-1, and the proximal end of the second conduit 702-2 may abut the second sealing surface 612-2, such that there is substantially no unswept volume within connector 208 to receive the flow phase between the distal end of the first conduit 702-1 and the first sealing surface 612-1, or between the proximal end of the second conduit 702-2 and the 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 a small volume (e.g., less than about 500 nL, less than about 100 nL, less than about 50 nL, less than about 1 nL, etc.) exists within the connector 208 to receive the flow 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.

[0073] In the illustrated example, each conduit 702 includes a coupling 710 located at the end portion of each conduit 702, which is received within a corresponding receiving portion 606 of the connector 208 and configured to connect each conduit 702 to 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 the corresponding receiving portion 606, such as by rotating the connector 208 relative to each coupling 710 (e.g., a user can grip a nut 712 positioned on each conduit 702 and a handle 604 on the connector 208 to rotate the connector 208 relative to each coupling 710, thereby threading each coupling 208 into the connector 710). Each coupling 710 is positioned at a selected distance away from the end of each conduit 702, such that the end of each conduit 702 is configured to fluidly seal with the corresponding sealing surface 612 of the connector 208 when each coupling 710 is positioned within the corresponding receiving portion 606. While the illustrated example shows a coupling 710 threaded into the receiving portion 606, alternative configurations (e.g., friction fit, snap-fit, etc.) can be used to fluidly connect the conduit 702 to the connector 208. As shown, the flowing phase 714 interacts with the sealing surface 612 as the flowing phase 714 flows through the first conduit 702-1, the connector 208, and the second conduit 702-2. In some cases, the conduit 702 may be retracted from the sealing surface 612, which can cause an unswept volume (e.g., dead volume) of the flowing 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. This unswept volume of mobile phase 714 in dead-volume-free and / or low-dead-volume connectors can result in broader chromatographic peaks.

[0074] The inventors investigated whether applying an electrochemical corrosion-resistant material to the first and second sealing surfaces of a connector would improve transmitter performance and extend transmitter life. LC-MS experiments were performed to evaluate how performance changed with transmitter aging, and the results are shown in... Figure 8A and Figure 8B The curve is shown in the graph. The experiment consisted of a sequence of 500 injections of 1 μg HeLa cell digestion solution. Additionally, the sequence included a blank run every 5 injections, resulting in a total of 575 injections. Therefore, the blank and performance runs were counted, and the transmitter underwent approximately 20% additional injections, which is not reflected in the curve. Figure 8A and Figure 8BThe curves shown are illustrated. In the LC-MS experiments, a 200 ng HeLa loading was used. Various connectors, including conductive joints, fluidly connected the emitter to the LC column. For each sample injection, an electrospray voltage was applied to the mobile phase via the conductive joints in the connectors to form a spray plume of ions for mass analysis (e.g., identifying the number of peptides within the sample).

[0075] Figure 8A and Figure 8B The effects of incorporating electrochemically resistant corrosion-resistant materials at the sealing surfaces of various connectors are demonstrated. Figure 8A An exemplary plot 800 is shown, plotting the peak width of a chromatographic peak obtained 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 is measured as half-width at half-maximum (FWHM). As shown, for a first experiment using a first connector with a titanium joint that does not include an electrochemically resistant material at the sealing surface, the peak width increases with the number of injections into the LC-MS system (e.g., as indicated by the solid line marked by the black circle). For a second experiment using a second connector with a titanium joint including an electrochemically resistant gold material at the sealing surface of the joint, the peak width increases slightly with the number of injections into the LC-MS system (e.g., as indicated by the dotted line marked by the hollow triangle). However, the peak width in the second experiment using the second connector does not increase to the same extent as in the first experiment using the first connector, which is believed to be due to the inclusion of an electrochemically resistant gold material at the sealing surface of the second connector. Additionally, for the third experiment using a third connector having 904L stainless steel, an electrochemically corrosion-resistant material included in the sealing surface of the conductive joint, the width of the chromatographic peak did not increase with the number of injections introduced into the LC-MS system (e.g., as indicated by the dashed line marked with "x"), which was attributed to the 904L stainless steel, an electrochemically corrosion-resistant material included in the sealing surface of the third connector.

[0076] The use of second and third connectors with electrochemically resistant materials on the sealing surfaces of the titanium connectors to reduce and / or eliminate the broadening of chromatographic peaks indicates that the electrochemically resistant materials included on the sealing surfaces of the titanium connectors reduce and / or eliminate corrosion of the connectors, and thus reduce and / or eliminate emitter degradation with long-term use.

[0077] Figure 8B The drawing was shown Figure 8ALC-MS analysis uses an illustrative plot 802 showing the amount of peptides identified by each emitter as a function of the number of injections into the LC-MS system using each emitter. As shown, for a first experiment using a first connector with a titanium joint that does not include an electrochemically resistant material at the sealing surface, the number of identified peptides decreases with increasing injections into the LC-MS system (e.g., as indicated by the solid line marked with a solid circle). For a second experiment using a second connector with a gold electrochemically resistant material included at the sealing surface of the conductive joint, the number of identified peptides decreases slightly with increasing injections into the LC-MS system (e.g., as indicated by the dashed line marked with a hollow triangle). However, the number of peptides identified in the second experiment using the second connector did not decrease by almost as much as the number identified in the first experiment using the first connector, which is believed to be due to the inclusion of the electrochemically resistant material gold at the sealing surface of the second connector. Additionally, for the third experiment using a third connector with a third connector having an electrochemically resistant 904L stainless steel material included in the sealing surface of the conductive joint, the number of peptides identified decreased only slightly with increasing number of injections introduced into the LC-MS system (e.g., as indicated by the dashed line marked with "x", which ended at injection 300 in the third experiment).

[0078] The reduction in the number of peptides recognized by the second and third connectors using electrochemically resistant materials is considered to further indicate that the electrochemically resistant materials included at the sealing surfaces of the connectors reduce and / or eliminate connector corrosion, and thus reduce and / or eliminate transmitter degradation with prolonged use. Therefore, connectors including electrochemically resistant materials at the first and second sealing surfaces of the conductive connectors reduce and / or prevent connector corrosion and transmitter degradation. This reduction and / or prevention of connector corrosion can further reduce and / or prevent a decrease in the sensitivity, efficiency, stability, and accuracy of the ESI method in LC-MS systems incorporating electrochemically resistant materials (e.g., by reducing and / or preventing mobile phase contamination by electrochemical products, peak broadening in chromatography, and / or reduced ion recognition in mass spectrometry).

[0079] Figure 9 A cross-sectional view of another exemplary embodiment of the electrochemical-resistant connector 208 is shown.

[0080] In addition to Figure 9 In addition to the fact that connector 602 is made of electrochemically corrosion-resistant material, Figure 9 and Figure 6B The same. Therefore, at least the first sealing surface 612-1 and the second sealing surface 612-2 include an electrochemical corrosion-resistant material for reducing and / or preventing corrosion of the joint 602 and / or degradation of the emitter 302.

[0081] In some examples, connector 602 also includes a sacrificial electrode ( Figure 9 (Not shown in the diagram), the sacrificial electrode interacts with the flowing phase and is configured to preferentially corrode relative to the electrochemically resistant material of the first sealing surface 612-1 and the second sealing surface 612-2. For example, the sacrificial electrode may comprise a material with a standard reduction potential lower than that of the electrochemically resistant material. In some examples, the sacrificial electrode comprises a structure (e.g., wire, rod, bar, coating, surface, etc.) made of titanium (or other metals having a lower standard reduction potential than that of the electrochemically resistant material) positioned within connector 208 or joint 602 (e.g., positioned within the first receiving portion 606-1, positioned within the second receiving portion 606-2, and / or positioned within the through-hole 608) for interaction with the flowing phase. Additionally or alternatively, when joint 602 comprises a first material (e.g., titanium) and a coating (e.g., coating 614), the coating comprises a second material applied over the first material at the first sealing surface 612-1 and the second sealing surface 612-2, the sacrificial electrode may comprise the first material, and the second material may comprise the electrochemically resistant material. This sacrificial electrode will preferentially corrode the electrochemically resistant materials 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.

[0082] Other suitable constructions of the sacrificial electrode can be used. For example, the sacrificial electrode may comprise conductive particles encapsulated within the emitter near the tip of the emitter in a packaged tip emitter construction. The conductive particles may be formed of or coated with a sacrificial material (e.g., a material whose standard reduction potential is lower than the standard reduction potential of the sealing surface of the conductive connector). In other examples, the sacrificial electrode comprises a sacrificial material coated on the inner surface of the emitter. In some examples, the electrochemical corrosion-resistant material at the sealing surface of the connector can be omitted by alternatively using a sacrificial electrode formed of a material whose standard reduction potential is lower than the standard reduction potential of the conductive connector.

[0083] Figure 10A and Figure 10B Various cross-sectional views of connector 208 are shown to depict exemplary methods of fabricating connector 208. The method includes forming a connector 602 configured to provide an electrospray voltage to the mobile phase when connector 602 is electrically connected to a power source. Figure 10AAs shown, forming connector 602 includes forming a first receiving portion 606-1 at the proximal end of connector 208 for receiving the distal end of a first conduit; forming a second receiving portion 606-2 at the distal end of connector 208 for receiving the proximal end of a second conduit; and forming a through hole 608 extending from the first receiving portion 606-1 to the second receiving portion 606-2. The first receiving portion 606-1 includes a first sealing surface 612-1 for contacting the flowing phase and fluid-sealing the distal end of the first conduit. Similarly, the second receiving portion 606-2 includes a second sealing surface 612-2 for contacting the flowing phase and fluid-sealing the proximal end of the second conduit. The first sealing surface 612-1 and the second sealing surface 612-2 each comprise an electrochemically corrosion-resistant material. That is, Figure 10A The connector 602 is made of an electrochemically corrosion-resistant material.

[0084] In other examples, forming the connector 602 includes a multi-step process of forming the connector 602 from a first material (e.g., a conductive material) and coating the first material with a second material, including an electrochemically corrosion-resistant material, at the first sealing surface 612-1 and the second sealing surface 612-2. For example, in Figure 10A In the first step shown, a connector 602 is formed from a first material including a conductive material. Figure 10B In the second step shown, 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 can be applied to the sealing surface 612 by any suitable method, such as, but not limited to, electroplating, sputtering coating, chemical vapor deposition (CVD), electron beam vapor deposition, or thin film deposition. Other suitable methods for fabricating connector 208 having a first sealing surface 612-1 and a second sealing surface 612-2 comprising an electrochemically corrosion-resistant material can be used. For example, the coating 614 can be additionally applied to other surfaces of the connector 602, such as the inner surface of the through-hole 608 and / or other surfaces within the receiving portion 606 (e.g., surfaces with dead volume).

[0085] 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 toward the inlet of any other ion manipulation device, such as an ion guide, ion optics, or ion mobility separator. In other modifications, the above system and method can be used with other electrospray ionization techniques, such as paper spray ionization and polymer spray ionization.

[0086] Those skilled in the art will recognize that while various illustrative examples have been described with reference to the accompanying drawings, various modifications and alterations may be made thereto without departing from the scope of the appended claims, and additional examples may be implemented. For example, certain features of one example described herein may be combined with or substituted for features of another example described herein. Therefore, this description and the drawings should be considered illustrative rather than restrictive. Furthermore, the drawings are not drawn to scale, so various features (e.g., via 608 and / or dead volume) may be exaggerated for the purpose of viewing and understanding the concepts described herein.

[0087] The advantages and features of this disclosure are further described through the following embodiments:

[0088] Example 1. A connector configured to fluidly connect a first conduit and a second conduit such that a mobile phase for liquid chromatography can flow through the first conduit and the second conduit, the connector including a conductive connector for providing an electrospray voltage to the mobile phase when the conductive connector is electrically connected to a power source, the conductive connector including: a first receiving portion for receiving a distal end of the first conduit, the first receiving portion including a first sealing surface that intersects with the mobile phase and fluidly seals with the distal end of the first conduit; a second receiving portion for receiving a proximal end of the second conduit, the second receiving portion including a second sealing surface that intersects with the mobile phase and fluidly seals with the proximal end of the second conduit; and a through-hole extending from the first receiving portion to the second receiving portion; wherein the first sealing surface and the second sealing surface each comprise an electrochemically resistant material.

[0089] Example 2. The connector according to Example 1, wherein the standard reduction potential of the electrochemical corrosion-resistant material is greater than the reduction potential of the standard hydrogen electrode (SHE).

[0090] Example 3. The connector according to Example 1, wherein the standard reduction potential of the electrochemical corrosion-resistant material is greater than the standard reduction potential of titanium.

[0091] Example 4. The connector according to Example 1, wherein the electrochemical corrosion-resistant material includes noble metals.

[0092] Example 5. The connector according to Example 1, wherein the electrochemical corrosion-resistant material comprises a metal alloy containing more than about 20 percent (20%) of nickel by weight.

[0093] Example 6. The connector according to Example 1, wherein the electrochemical corrosion-resistant material comprises a metal alloy containing less than about one percent (1%) of iron by weight.

[0094] Example 7. The connector according to Example 1, wherein the electrochemical corrosion-resistant material comprises gold.

[0095] Example 8. The connector according to Example 1, wherein the electrochemical corrosion-resistant material comprises 904L stainless steel.

[0096] Example 9. The connector according to Example 1, wherein the conductive connector comprises a first material and a second material, the second material forming 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.

[0097] Example 10. The connector according to Example 9, wherein the first material comprises titanium.

[0098] Example 11. The connector according to Example 9, wherein the first material is conductive.

[0099] Example 12. The connector according to Example 9, wherein the conductive connector further includes the second material on the first material on the inner surface of the through hole.

[0100] Example 13. The connector according to Example 9, wherein the coating is applied to the first material on the first sealing surface and the second sealing surface by electroplating or sputtering.

[0101] Example 14. The connector according to Example 1, wherein the conductive connector comprises the electrochemically corrosion-resistant material.

[0102] Example 15. The connector according to Example 1, wherein the connector is a low dead volume or dead volume connector.

[0103] Example 16. The connector according to Example 1, wherein the conductive joint further includes a sacrificial electrode that interacts with the flow phase and is configured to preferentially corrode the electrochemically resistant material relative to the first sealing surface and the second sealing surface.

[0104] Example 17. The connector according to Example 16, wherein the sacrificial electrode comprises a metal having a lower standard reduction potential than the electrochemical corrosion-resistant material.

[0105] Example 18. The connector according to Example 16, wherein the conductive connector comprises a first material and a second material, the second material forming 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 electrochemically resistant material.

[0106] 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; a connector positioned between and fluidly connected to the first and second conduits to allow a mobile phase to flow through the first and second conduits to the ESI emitter, the connector including a conductive joint comprising: a first receiving portion for receiving a distal end of the first conduit, the first receiving portion including a first sealing surface configured to interact with the mobile phase and fluidly seal the distal end of the first conduit; a second receiving portion for receiving a proximal end of the second conduit, the second receiving portion including a second sealing surface configured to interact with the mobile phase and fluidly seal the proximal end of the second conduit; and a through-hole extending from the first receiving portion to the second receiving portion; wherein the first sealing surface and the second sealing surface each comprise an electrochemically resistant material; and a power source electrically connected to the conductive joint to provide an electrospray voltage to the mobile phase.

[0107] Example 20. The system according to Example 19, the system further includes: a chromatographic column, the chromatographic column including a stationary phase.

[0108] Example 21. The system according to Example 20, wherein the chromatographic column is positioned upstream of the connector such that the outlet of the chromatographic column is fluidly connected to the first conduit.

[0109] Example 22. The system according to Example 20, wherein the chromatographic column is positioned downstream of the connector such that the inlet of the chromatographic column is fluidly connected to the second conduit.

[0110] Example 23. The system according to Example 19, wherein the standard reduction potential of the electrochemical corrosion-resistant material is greater than the threshold standard reduction potential.

[0111] Example 24. The system according to Example 23, wherein the threshold standard reduction potential is the reduction potential of the standard hydrogen electrode (SHE).

[0112] Example 25. The system according to Example 23, wherein the threshold standard reduction potential is the standard reduction potential of titanium.

[0113] Example 26. The system according to Example 19, wherein the conductive connector includes a first material and a second material, the second material forming a coating on the first material at the first sealing surface and the second sealing surface, the second material including the electrochemical corrosion-resistant material.

[0114] Example 27. The system according to Example 19, wherein the conductive connector comprises the electrochemical corrosion-resistant material.

[0115] Example 28. A method of manufacturing a connector configured to fluidly connect a first conduit and a second conduit such that a mobile phase for liquid chromatography can flow through the first conduit and the second conduit, the method comprising: forming a conductive joint configured to provide an electrospray voltage to the mobile phase when the conductive joint is electrically connected to a power source, the conductive joint comprising: a first receiving portion located at a proximal end of the connector for receiving a distal end of the first conduit, the first receiving portion including a first sealing surface for interacting with the mobile phase and fluidly sealing the distal end of the first conduit; a second receiving portion located at a distal end of the connector for receiving a proximal end of the second conduit, the second receiving portion including a second sealing surface for interacting with the mobile phase and fluidly sealing the proximal end of the second conduit; and a through-hole extending from the first receiving portion to the second receiving portion; wherein the first sealing surface and the second sealing surface each comprise an electrochemically resistant material.

[0116] Example 29. The method according to Example 28, wherein the standard reduction potential of the electrochemical corrosion-resistant material is greater than the threshold standard reduction potential.

[0117] Example 30. The method according to Example 28, wherein forming the conductive connector comprises: forming the conductive connector from a first material; and coating the first material, including the electrochemical corrosion-resistant material, onto the first sealing surface and the second sealing surface with a second material.

[0118] Example 31. The method according to Example 30, wherein the coating includes electroplating or sputtering the first sealing surface and the second sealing surface with the electrochemical corrosion-resistant material.

[0119] Example 32. The method according to Example 28, wherein forming the conductive connector includes forming the conductive connector from the electrochemical corrosion-resistant material.

Claims

1. A connector configured to fluidly connect a first conduit and a second conduit such that a mobile phase for liquid chromatography can flow through the first conduit and the second conduit, the connector including a conductive connector for providing an electrospray voltage to the mobile phase when the conductive connector is electrically connected to a power source, the conductive connector comprising: A first receiving portion for receiving the distal end of the first conduit, the first receiving portion including a first sealing surface that interacts with the flow and fluidly seals the distal end of the first conduit; A second receiving portion, the second receiving portion for receiving the proximal end of the second conduit, the second receiving portion including a second sealing surface, the second sealing surface intersecting with the flow phase and fluid-sealing the proximal end of the second conduit; and A through-hole extending from the first receiving portion to the second receiving portion; The first sealing surface and the second sealing surface each comprise an electrochemically corrosion-resistant material.

2. The connector according to claim 1, wherein the standard reduction potential of the electrochemical corrosion-resistant material is greater than the reduction potential of the standard hydrogen electrode (SHE).

3. The connector according to claim 1, wherein the standard reduction potential of the electrochemical corrosion-resistant material is greater than the standard reduction potential of titanium.

4. The connector according to 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 containing more than about 20 percent (20%) of 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%) of iron by weight.

7. The connector according to claim 1, wherein the electrochemical corrosion-resistant material comprises gold.

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

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

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

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

12. The connector according to claim 1, wherein the conductive joint is formed of the electrochemically corrosion-resistant material.

13. The connector of claim 1, wherein the conductive joint further comprises a sacrificial electrode, the sacrificial electrode being in contact with the flow phase and configured to preferentially corrode the electrochemically resistant material relative to the first sealing surface and the second sealing surface.

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

15. The connector of claim 13, wherein the conductive joint comprises a first material and a second material, the second material forming 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 electrochemically resistant material.

16. A system for analyzing a sample by liquid chromatography-mass spectrometry, the system comprising: First catheter; Second catheter; Electrospray ionization (ESI) emitter; A connector, positioned between and fluidly connected to the first and second conduits to allow the mobile phase to flow through the first and second conduits to the ESI emitter, the connector including a conductive connector comprising: A first receiving portion for receiving the distal end of the first conduit, the first receiving portion including a first sealing surface configured to interact with the flow and fluidly seal the distal end of the first conduit; A second receiving portion, the second receiving portion for receiving the proximal end of the second conduit, the second receiving portion including a second sealing surface configured to interact with the flow and fluid-tightly seal the proximal end of the second conduit; and A through-hole extending from the first receiving portion to the second receiving portion; wherein the first sealing surface and the second sealing surface each comprise an electrochemically corrosion-resistant material; and A power source, electrically connected to the conductive connector, is provided with an electrospray voltage to the mobile phase.

17. The system of claim 16, further comprising: A chromatographic column, the chromatographic column comprising a stationary phase.

18. The system of claim 17, wherein the chromatographic column is positioned upstream of the connector such that the outlet of the chromatographic column is fluidly connected to the first conduit.

19. The system of claim 17, wherein the chromatographic column is positioned downstream of the connector such that the inlet of the chromatographic column is fluidly connected to the second conduit.

20. A method of manufacturing a connector, the connector being configured to fluidly connect a first conduit and a second conduit such that a mobile phase for liquid chromatography can flow through the first conduit and the second conduit, the method comprising: A conductive connector is formed, the conductive connector being configured to provide an electrospray voltage to the mobile phase when the conductive connector is electrically connected to a power source, the conductive connector comprising: A first receiving portion, located at the proximal end of the connector, is used to receive the distal end of the first conduit. The first receiving portion includes a first sealing surface for contacting the flow phase and fluidly sealing the distal end of the first conduit. A second receiving portion, located at the distal end of the connector, for receiving the proximal end of the second conduit, the second receiving portion including a second sealing surface for contacting the flow phase and for fluid sealing with the proximal end of the second conduit; and A through-hole extending from the first receiving portion to the second receiving portion; wherein the first sealing surface and the second sealing surface each comprise an electrochemically corrosion-resistant material.

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