Systems and methods for introducing solvents to a sampling interface

Abstract

A solvent delivery system for an open port interface (OPI) includes a first diverter which includes a wash solvent inlet, a carrier solvent inlet, and a first diverter outlet. A wash solvent pump is fluidically coupled to the wash solvent inlet. A carrier solvent pump is fluidically coupled to the carrier solvent inlet. A second diverter includes a second diverter inlet fluidically coupled to the first diverter outlet. An OPI port is configured to be coupled to an OPI. A waste outlet is configured to be coupled to a waste container.

Description

SYSTEMS AND METHODS FOR INTRODUCING SOLVENTS TO A SAMPLINGINTERFACEReference to Related Applications

[0001] This application is being filed as a PCT International Patent Application and claims the benefit of and priority to U.S. Provisional Patent Application No. 63 / 520,951, filed on August 22, 2023, the disclosure of which is incorporated herein by reference in its entirety.Introduction

[0002] A sampling interface captures, mixes, and dilutes a captured sample with a carrier solvent (also referred to as a transport liquid), and delivers the resulting sample dilution to an ionization source for ionization, for example, in a mass spectrometer. Sampling interfaces are reported as a convenient mass spectrometry (MS) sampling interface for discrete liquid droplets, from the nanoliter to the microliter range. Different combinations of carrier solvents (for receiving a sample) and wash solvents (for cleaning the sampling interface and associated conduits) may be used. When different types of solvents (carrier solvent and wash solvent) are mixed, the mixture may surge out of the sampling interface, triggering a drip sensor and causing an error.Summary

[0003] In one aspect, the technology relates to a solvent delivery system for an open port interface (OPI), the solvent delivery system includes: a first diverter including a wash solvent inlet, a carrier solvent inlet, and a first diverter outlet; a wash solvent pump fluidically coupled to the wash solvent inlet; a carrier solvent pump fluidically coupled to the carrier solvent inlet; and a second diverter includes: a second diverter inlet fluidically coupled to the first diverter outlet; an OPI port configured to be coupled to an OPI; and a waste outlet configured to be coupled to a waste container. In an example, the second diverter further includes a vacuum pump outlet and wherein the solvent delivery system further includes a vacuum pump fluidically coupled to the vacuum pump outlet, wherein the vacuum pump outlet is selectively couplable to the OPI port via the second diverter and wherein the vacuum pump is configured to generate a vacuum on the OPI to draw liquid from the OPI and to a vacuum pump discharge. In another example, the solvent delivery system further includes avacuum pump check valve disposed between the vacuum pump outlet and the vacuum pump. In yet another example, the solvent delivery system further includes a waste check valve disposed downstream of the waste outlet. In still another example, the solvent delivery system further includes a controller for setting the solvent delivery system in a plurality of flow configurations, wherein the plurality of flow configurations includes at least one of: a carrier configuration; a flush configuration; a prime configuration; and a wash configuration.

[0004] In another example of the above aspect, when the controller sets the system to the carrier configuration: the carrier solvent pump is fluidically coupled to the OPI via the carrier solvent inlet, the first diverter outlet, and the second diverter inlet, and the OPI port; and the controller activates the carrier solvent pump to deliver a carrier solvent from a carrier solvent reservoir to the OPI. In an example, the solvent delivery system further includes a vacuum pump fluidically coupled to the OPI via a vacuum pump outlet on the second diverter and the OPI port, and wherein when the controller sets the system to the flush configuration, the controller activates the vacuum pump to draw at least one of an air and a liquid from the OPI to the vacuum pump. In another example, when the controller sets the system to the prime configuration: only one of: (a) the carrier solvent pump is fluidically coupled to the waste container via the carrier solvent inlet, the first diverter outlet, and the second diverter inlet, and the waste outlet; and (b) the wash solvent pump is fluidically coupled to the waste container via the wash solvent inlet, the first diverter outlet, and the second diverter inlet, and the waste outlet; and the controller activates only one of the carrier solvent pump and the wash solvent pump to deliver only one of a carrier solvent and a wash solvent from only one of a carrier solvent reservoir and a wash solvent reservoir to the waste container. In yet another example, when the controller sets the system to the wash configuration: the wash solvent pump is fluidically coupled to the OPI via the wash solvent inlet, the first diverter outlet, and the second diverter inlet, and the OPI port; and the controller activates the wash solvent pump to deliver a wash solvent from a wash solvent reservoir to the OPI. In still another example, the vacuum pump includes a vacuum pump discharge fluidically coupled to the waste container.

[0005] In another example of the above aspect, the controller is configured to set the system in the flush configuration and the prime configuration simultaneously.

[0006] In another aspect, the technology relates to a solvent delivery system for a sampling interface, the solvent delivery system includes: a solvent pump subsystem; a diverterfluidically coupled to the solvent pump subsystem and to the sampling interface; a vacuum pump fluidically coupled to the diverter; a waste line fluidically coupled to each of the vacuum pump and the diverter; at least one controller operatively coupled to the solvent pump subsystem, the diverter, and the vacuum pump; and a memory coupled to the at least one controller, the memory storing instructions that, when executed by the controller, performs a set of operations including: setting the diverter in one of a plurality of flow configurations; and at least one of activating and disabling at least one of the solvent pump subsystem and the vacuum pump. In an example, the plurality of flow configurations includes: a carrier configuration; a flush configuration; a prime configuration; and a wash configuration. In another example, when the controller sets the diverter in the carrier configuration, the set of operations further includes: activating the solvent pump subsystem to deliver a carrier solvent to the sampling interface via the diverter; and disabling the vacuum pump. In yet another example, when the controller sets the diverter in the flush configuration, the set of operations further includes: disabling the solvent pump subsystem; and activating the vacuum pump to generate a vacuum at the sampling interface via the diverter and direct a discharge from the vacuum pump to the waste line. In still another example, when the controller sets the diverter in the prime configuration, the set of operations further includes: activating the solvent pump subsystem to deliver at least one of a carrier solvent and a wash solvent to the waste line via the diverter; and disabling the vacuum pump.

[0007] In another example of the above aspect, when the controller sets the diverter in the wash configuration, the set of operations further includes: activating the solvent pump subsystem to deliver a wash solvent to the sampling interface via the diverter; and disabling the vacuum pump.

[0008] In another aspect, the technology relates to a method of operating a solvent delivery system for a sampling interface, the method includes: receiving a configuration selection signal; and based at least in part on the configuration cycle selection signal: selecting a diverter flow path from a plurality of diverter flow paths of a diverter; sending a signal to the diverter to set the diverter in the selected diverter flow path; selecting a solvent; only one of activating and deactivating a solvent pump associated with the solvent, wherein the solvent pump is fluidically coupled to the diverter, wherein activation of the solvent pump delivers the selected solvent to the diverter; and only one of activating and deactivating a vacuum pump fluidically coupled to the diverter. In an example, the method further includesdeactivating the solvent pump based at least in part on a signal received from a drip sensor associated with the sampling interface. In another example, the diverter includes a pair of configurable diverters, wherein a first diverter of the pair of configurable diverters is fluidically coupled to the sampling interface, wherein a second diverter of the pair of configurable diverters is fluidically coupled to the vacuum pump, and wherein selecting a diverter flow path includes changing an internal flow path of at least one of the first diverter and the second diverter.Brief Description of the Drawings

[0009] FIG. 1 is a schematic view of an example system combining acoustic droplet ejection (ADE) with an open port interface (OPI) sampling interface and electrospray ionization (ESI) source.

[0010] FIG. 2 is a schematic view of a solvent delivery system for a sampling interface.

[0011] FIG. 2A is a schematic view of the solvent delivery system of FIG. 2 in a carrier configuration.

[0012] FIG. 2B is a schematic view of the solvent delivery system of FIG. 2 in a flush configuration.

[0013] FIG. 2C is a schematic view of the solvent delivery system of FIG. 2 in a prime configuration.

[0014] FIG. 2D is a schematic view of the solvent delivery system of FIG. 2 in a wash configuration.

[0015] FIG. 3 depicts a method of operating a solvent delivery system for a sampling interface.

[0016] FIG. 4 is a schematic view of an example of a solvent delivery system for an OPI.

[0017] FIG. 4A is a schematic view of the solvent delivery system of FIG. 4 in a carrier configuration.

[0018] FIG. 4B is a schematic view of the solvent delivery system of FIG. 4 in a flush configuration.

[0019] FIG. 4C is a schematic view of the solvent delivery system of FIG. 4 in a prime configuration.

[0020] FIG. 4D is a schematic view of the solvent delivery system of FIG. 4 in a wash configuration.

[0021] FIG. 5 depicts an example of a suitable operating environment in which one or more of the present examples can be implemented.Detailed Description

[0022] The technologies described contemplate a solvent delivery system that may selectively deliver a carrier solvent or a wash solvent for various purposes to a sampling interface. Carrier solvent contains a relatively high concentration of organic solvent; carrier solvents may include methanol, acetonitrile, isopropyl alcohol, or other types of carrier solvents that may also include certain additives. Wash solvent contains a relatively high concentration of water; wash solvents may include a mixture of carrier solvent (with certain additives) mixed with a high concentration of water. During the transition phase between these two liquids, intermittent trigger failures may arise by the trigger of a drip sensor that is mounted close to the sampling interface. The interaction of the high organic solvent of the carrier solvent and high water content of the wash solvent appears to cause the mixture to more easily reach and trigger the drip sensor. To reduce or avoid the likelihood of this condition, a pump (such as a vacuum pump, a diaphragm pump, or other type of waste pump) may be incorporated into the solvent delivery system to purge any liquid that is in the sampling interface and the associated liquid conduits, prior to switching to a different solvent. One or more valves of various types may also be utilized in connection with the pump. Further, the various conduits may be fdled with the appropriate solvent at various times before, during, and after a sampling procedure.

[0023] FIG. 1 is used for illustrative purposes to depict and locate the various components of an analysis system 100 relative to each other. Relevant to the present disclosure, a sampling interface (in this case, an OPI 104) is in a downward-facing orientation, where a sample inlet 128 thereof faces downwards to receive a sample. Upward-facing orientations of the OPI 104 are also contemplated in such systems 100 and similar analysis systems, as would be known to a person of skill in the art.

[0024] For illustrative purposes, FIG. 1 is a schematic view of an example analysis system 100 combining an ADE 102 with an OPI sampling interface 104 and ESI source 114. The system 100 may be a mass analysis instrument such as a mass spectrometry device that is for ionizing and mass analyzing analytes received within an open end of the sampling OPI. Such a system 100 is described, for example, in U.S. Pat. No. 10,770,277, the disclosure of which is incorporated by reference herein in its entirety. The ADE 102 includes an acoustic ejector 106 that is configured to eject a droplet 108 from a reservoir of a well plate 112 into the open end of sampling OPI 104. Other contactless ejectors may also be utilized as may sample introduction systems that do not utilize ejection of samples.

[0025] As shown in FIG. 1, the example system 100 generally includes the sampling OPI 104 in liquid communication with the ESI source 114 for discharging a liquid containing one or more sample analytes (e.g., via electrospray electrode 116) into an ionization chamber 118, and a mass analyzer detector (depicted generally at 120) in communication with the ionization chamber 118 for downstream processing and / or detection of ions generated by the ESI source 114. Due to the configuration of the nebulizer nozzle 138 and electrospray electrode 116 of the ESI source 114, samples ejected therefrom are transformed into the gas phase. A liquid handling system 122 (e.g., including one or more pumps 124a, 124b and one or more transfer conduits 125) provides for the flow of liquid from two or more solvent reservoirs 126a, 126b to the sampling OPI 104 and from the sampling OPI 104 to the ESI source 114. As ESI sources 114 allow for the formation of multiple charged ions and are, therefore, more applicable to a variety of applications, they are described within the application for consistency. The technologies described herein, however, may also be utilized for systems that incorporate a plurality of atmospheric pressure chemical ionization (APCI) sources.

[0026] In the depicted configuration, the solvent pumps 124a, 124b, and solvent reservoirs 126a, 126b form a part of a solvent delivery subsystem 131. Other components of the solvent delivery subsystem 131 include a diverter 133, a vacuum pump 135 fluidically coupled to the sampling OPI 104, and a waste container 137. The components and functionality of the solvent delivery subsystem 131 are described in more detail further in this application. The solvent reservoir 126a contains a wash solvent while the solvent reservoir 126b contains a carrier solvent (transport liquid). More than two solvent reservoirs may be used, for example, if a system utilizing multiple types of carrier solvents is desired. The solvent reservoirs 126a,126b can be fluidically coupled to the sampling OPI 104 via a supply conduit 127 through which the liquid can be delivered at a selected volumetric rate by the pumps 124a, 124b (e.g., a reciprocating pump, a positive displacement pump such as a rotary, gear, plunger, piston, peristaltic, diaphragm pump, or other pump such as a gravity, impulse, pneumatic, electrokinetic, and centrifugal pump). As discussed in detail below, the flow of liquid into and out of the sampling OPI 104 occurs within an internal volume 104a of the OPI 104 that is accessible at an open sample inlet 128 such that one or more samples 108 (here, in the form of sample droplets) can be introduced into a liquid boundary at the open sample inlet 128 and subsequently delivered to the ESI source 114. The diluted liquid samples LS exit the OPI 104 via a removal conduit 129 disposed therein and fluidically coupled to the transfer conduit 125. Further, flow out of the pumps 124a, 124b may be adjusted, for example, based on the number of ESI sources 114 operating at a given time, or otherwise as required or desired for a particular application.

[0027] The system 100 includes an ADE 102 that is configured to generate acoustic energy that is applied to a liquid contained within a reservoir 110 that causes one or more droplets 108 to be ejected from the reservoir 110 into the open sample inlet 128 of the sampling OPI 104. A controller 130 can be operatively coupled to and configured to operate any aspect of the system 100. This enables the acoustic transducer of the ADE 106 to inject droplets 108 into the sampling OPI 104 as otherwise discussed herein substantially continuously or for selected portions of an experimental protocol by way of non-limiting example. As noted above other types of sample introduction systems may be utilized. ADE 102 and other noncontact ejection systems are particularly advantageous, however, because of the high sample throughput that may be achieved. Controller 130 can be, but is not limited to, a microcontroller, a computer, a microprocessor, or any device capable of sending and receiving control signals and data. Wired or wireless connections between the controller 130 and the remaining elements of the system 100 are not depicted but would be apparent to a person of skill in the art.

[0028] As shown in FIG. 1, the ESI source 114 can include a source 136 of pressurized gas (e.g., nitrogen, air, or a noble gas) that supplies a high velocity nebulizing gas flow to the nebulizer nozzle 138 that surrounds the outlet tip of the electrospray electrode 116. As depicted, the electrospray electrode 116 protrudes from a distal end of the nebulizer nozzle 138. The pressured gas interacts with the liquid discharged from the electrospray electrode116 to enhance the formation of the sample plume and the ion release within the plume for sampling by mass analyzer detector 120, e.g., via the interaction of the high speed nebulizing flow and jet of liquid sample (e.g., analyte -solvent dilution). The liquid discharged include the samples received from each reservoir 110 of the well plate 112. The liquid samples LS are diluted with the carrier solvent and may be separated from other samples by volumes of the solvent S depending on introduction rate of the liquid samples LS. As such, since flow of the solvent S moves the diluted liquid samples LS from the OPI 104 to the ESI source 114, the solvent S may also be referred to herein as a transport liquid. The nebulizer gas can be supplied at a variety of flow rates, for example, in a range from about 0.1 L / min to about 40 L / min, which can also be controlled under the influence of controller 130 (e.g., via opening and / or closing valve 140).

[0029] It will be appreciated that the flow rate of the nebulizer gas can be adjusted (e.g., under the influence of controller 130) such that the flow rate of liquid within the sampling OPI 104 can be adjusted based, for example, on suction / aspiration force generated by the interaction of the nebulizer gas and the analyte-solvent dilution as it is being discharged from the electrospray electrode 116 (e.g., due to the Venturi effect / shock formation). The ionization chamber 118 can be maintained at atmospheric pressure, though in some examples, the ionization chamber 118 can be evacuated to a pressure lower than atmospheric pressure.

[0030] It will also be appreciated by a person skilled in the art and in light of the teachings herein that the mass analyzer detector 120 can have a variety of configurations. Generally, the mass analyzer detector 120 is configured to process (e.g., filter, sort, dissociate, detect, etc.) sample ions generated by the ESI source 114. By way of non-limiting example, the mass analyzer detector 120 can be a triple quadrupole mass spectrometer, or any other mass analyzer known in the art and modified in accordance with the teachings herein. Other nonlimiting, exemplary mass spectrometer systems that can be modified in accordance with various aspects of the systems, devices, and methods disclosed herein can be found, for example, in an article entitled "Product ion scanning using a Q-q-Q linear ion trap (Q TRAP) mass spectrometer," authored by James W. Hager and J. C. Yves Le Blanc and published in Rapid Communications in Mass Spectrometry (2003; 17: 1056-1064); and U.S. Pat. No. 7,923,681, entitled "Collision Cell for Mass Spectrometer," the disclosures of which are hereby incorporated by reference herein in their entireties.

[0031] Other configurations, including but not limited to those described herein and others known to those skilled in the art, can also be utilized in conjunction with the systems, devices, and methods disclosed herein. For instance, other suitable mass spectrometers include single quadrupole, triple quadrupole, ToF, trap, and hybrid analyzers. It will further be appreciated that any number of additional elements can be included in the system 100 including, for example, an ion mobility spectrometer (e.g., a differential mobility spectrometer) that is disposed between the ionization chamber 118 and the mass analyzer detector 120 and is configured to separate ions based on their mobility difference in high- field and low-field). Additionally, it will be appreciated that the mass analyzer detector 120 can comprise a detector that can detect the ions that pass through the analyzer detector 120 and can, for example, supply a signal indicative of the number of ions per second that are detected.

[0032] Further, in other configurations, a sampling interface other than an OPI 104 may be utilized in conjunction with the systems, devices, and methods disclosed herein. OPI sample transport flow relies on pressure differential set up across the transfer conduit 125 by nebulizer gas expanding past the transfer conduit 125 termination, e.g., at electrospray electrode 116, though nebulizers nozzles that do not use electrospray electrodes (e.g., APCI) are also contemplated for use with the technologies described herein. Nebulizer gas is expanding from the nebulizer nozzle 138, the nozzle size and nebulizer gas pressure determine the gas flowrate through the nozzle 138. Increasing the nebulizer gas flowrate generally improves the vacuum at the transfer conduit 125 termination and hence the pressure differential across the transfer conduit 125. Increasing the pressure differential (e.g., higher vacuum at the nozzle 138) increases the transport flow and improves sample throughput.

[0033] FIG. 2 is a schematic view of a solvent delivery system 200 for a sampling interface 202. In FIG. 2, fluid conduits between components are depicted as solid lines. Various types of sampling interfaces 202 may be utilized, as described herein, such as an OPI, or pumpbased or syringe-based sample introduction systems. Regardless, the sampling interface 202 is connected to the diverter 204 at a sampling interface port 204a. The diverter 204 may be or include one or more flow control valves, sample injector valves (such as utilized in high- performance liquid chromatography (HPLC)), valves on chips, etc., as required or desired to enable the various flow configurations described herein. In other examples, valves may be selector-type valves, or other multiposition valves that may utilize manual, pneumatic, orelectrical actuators. A solvent pump or delivery subsystem 206 is also fluidically coupled to the diverter 204 at a solvent inlet 206a. The solvent delivery subsystem 206 may include one pump with one or more selectable valves to control aspiration of liquid (solvent) from one or more solvent reservoirs 208a, 208b. For illustrative purposes, the solvent reservoirs are described as a wash solvent reservoir 208a and a carrier solvent reservoir 208b. Solvent degassers 210a, 210b may be utilized between the reservoirs 208a, 208b and solvent delivery subsystem 206, as known in the art. A vacuum pump 212 is coupled to the diverter 204 at a vacuum pump outlet 212a, and a check valve 214 may be installed on the vacuum line 216 between the diverter 204 and the vacuum pump 212. The vacuum pump 212 is connected to a waste container 218 via a vacuum pump discharge 220. The waste container 218 is also connected to the diverter 204 at a waste outlet 218a. A check valve 224 is installed on a waste line 222 prevents discharge from the vacuum pump 212 from entering the diverter 204. A controller 226 may control operation of the solvent pump subsystem 206 (e.g., activation and deactivation of one or more pumps, opening or closing of one or more valves, etc.), enabling or disabling the vacuum pump 212, and setting a flow configuration of the diverter 204, and is depicted coupled to such components with wires depicted in dot-dash lines. In examples, the controller 226 of FIG. 2 may be the controller 130 of the analysis system 100 depicted in FIG. 1. In certain embodiments, a drip sensor S may be utilized to detect drips at the sampling interface 202, and may be communicatively coupled to the controller 130 and / or the solvent delivery subsystem 206 to terminate delivery of solvent if a drip from the sampling interface 202 is detected.

[0034] FIGS. 2A-2D depict various flow configurations through the diverter 204 of FIG. 2. The configurations include a carrier configuration, a flush configuration, a prime configuration, and a wash configuration, depicted in FIGS. 2A-2D, respectively. In general, the carrier configuration is utilized when samples are received in the sampling interface 202 and is characterized in that, among other things, carrier solvent from the carrier solvent reservoir 208b is delivered to the sample interface 202. In general, the flush configuration is utilized to purge or flush solvent (and any residual sample(s)) from the solvent delivery subsystem 200 by activating the vacuum pump 212 to draw out liquids present in the sampling interface 202. In general, the prime configuration is utilized to fill the solvent delivery subsystem 200 by delivering carrier or wash solvent through the diverter 204 and to the waste container 218. In examples, the flush configuration may also be operated during the prime configuration, thereby simultaneously drawing any liquid from the samplinginterface 202 with the vacuum pump. Operating the flush configuration simultaneously with the prime configuration may improve operational times for the solvent delivery subsystem 200. In general, the wash configuration is utilized to deliver wash solvent from the wash solvent reservoir 208a to the sampling interface 202, and ultimately to the ESI (described above in the context of FIG. 1). This washes carrier solvent and any lingering samples from the sampling interface 202 and transfer line to the ESI, and also extends the life of the transfer line by preventing clogging. Lingering samples within the sampling interface or transfer line could also adversely affect the testing of subsequent samples, and are thus removed during the wash configuration. In examples, in the wash configuration, gas is released from source 136 (as depicted in FIG. 1) to draw wash liquid through the transfer conduit 125 (FIG. 1) without operating the ESI as would be done for sample analysis. Further descriptions of each configuration, as well as the various flow paths through the diverter 204 and between the various components of the solvent delivery subsystem 200 is described in FIGS. 2A-2D.

[0035] As noted above with regard to FIG. 2, various fluid (liquid and in some cases, gases such as air) conduits between components as solid lines are depicted in FIGS. 2A-2D. These conduits fluidically couple the connected components. Further, dashed lines depict configurable flow paths within the diverter 204 that are used to control and set the various flow path configurations between the various components. These flow paths may be described as being “created” or “configured” or like terms; such terms contemplate the opening or closing of one or more valves, or otherwise directing fluid flow through available flow paths within the diverter 204 to achieve the described results. The elements and components described in FIGS. 2A-2D are described above with regard to FIG. 2 and are not necessarily described further. Additionally, in the context of FIGS. 2A-2D, certain components, such as the solvent pump subsystem 206 and the vacuum pump 212 may be activated (or enabled) or deactivated (or disabled) during a particular flow configuration. As used herein, the terms “activated” or “enabled” (or the infinitive or gerund versions of those words) or “deactivated” or “disabled” (or the infinitive or gerund versions of those words) contemplate an action that places the associated component within the identified operational state or, if the associated component is already in the operational state, a non-action that allows the component to remain in that operational state (e.g., taking no action to change the operational state). Paths of fluids (liquids and / or gases) in each flow configuration are depicted by arrows.

[0036] FIG. 2A is a schematic view of the solvent delivery system 200 of FIG. 2 in a carrier configuration. When the controller 226 sets the diverter 204 in the carrier configuration, flow path 228 is created to fluidically couple the solvent pump subsystem 206 to the sampling interface 202 via the diverter 204. The solvent pump subsystem 206 is activated to deliver a carrier solvent from the carrier solvent reservoir 208b to the sampling interface 202. The vacuum pump 212 is disabled.

[0037] FIG. 2B is a schematic view of the solvent delivery system 200 of FIG. 2 in a flush configuration. When the controller 226 sets the diverter 204 in the flush configuration, flow path 232 is created to fluidically couple the sampling interface 202 to the vacuum pump 212 via the diverter 204. The solvent pump subsystem 206 is disabled. The vacuum pump 212 is activated to generate a vacuum at the sampling interface 202 via the diverter 204 and direct a discharge from the vacuum pump 212 to the waste line 222 and waste container 218. The discharge may include any gas or liquid drawn from the sampling interface 202.

[0038] FIG. 2C is a schematic view of the solvent delivery system 200 of FIG. 2 in a prime configuration. When the controller 226 sets the diverter 204 in the prime configuration, flow path 230 is created to fluidically couple the solvent pump subsystem 206 to the waste line 222 via the diverter 204. The solvent pump subsystem 206 is activated to deliver only one of a carrier solvent from the carrier solvent reservoir 208b and a wash solvent from the wash solvent reservoir 208a to the waste line 222 and ultimately the waste container 218. In FIG. 2C, flow from both reservoirs 208a, 208b is depicted for illustrative purposes, but only a single flow path would be utilized in practice. The solvent delivered may be as required or desired for a particular procedure of the solvent delivery subsystem 200. In some examples, the prime configuration may include activation of the solvent pump subsystem 206 so as to alternatively deliver one type of solvent (e.g., wash solvent), followed by the other type of solvent (e.g., carrier solvent). The vacuum pump 212 is disabled, but in examples, may be activated if the system 200 is being simultaneously operated in both the flush and prime configurations.

[0039] FIG. 2D is a schematic view of the solvent delivery system 200 of FIG. 2 in a wash configuration. When the controller 226 sets the diverter 204 in the wash configuration, flow path 228 is created to fluidically couple the solvent pump subsystem 206 to the sampling interface 202 via the diverter 204. The solvent pump subsystem 206 is activated to deliver awash solvent from the wash solvent reservoir 208a to the sampling interface 202. The vacuum pump 212 is disabled.

[0040] FIG. 3 depicts a method 300 of operating a solvent delivery system for a sampling interface. The method 300 begins with operation 302, receiving a configuration selection signal. The signal may be initiated by a user selection, as required or desired for a particular application. In other examples, the signal may be initiated by a program operated by the controller of an associated analysis system. The program may be configured to change flow configurations during certain operational periods or at certain operation times (e.g., when changing between sample well plates, after a predetermined length of time, after a predetermined number of samples are processed, at system start-up or shut-down, etc.). Based at least in part on the received configuration selection signal, operations 304-312 may be performed. A diverter flow path is selected from a plurality of diverter flow paths of a diverter, operation 304. As described elsewhere herein, these configurations may include a carrier configuration, a flush configuration, a prime configuration, and a wash configuration. In operation 306, a signal is sent to the diverter to set the diverter to the selected diverter flow path. The method continues with operation 308, selecting a solvent, which may be a carrier solvent or a wash solvent. In operation 310, the method 300 includes activating a solvent pump associated with the solvent, wherein the solvent pump is fluidically coupled to the diverter. In other examples such as in a single-pump solvent delivery subsystem, operation 310 may also include actuating a selectable valve associated with the solvent selected in operation 308. Regardless, activation of the solvent pump delivers the selected solvent to the diverter. From the diverter, the selected flow path enables delivery of the solvent to the selected component or element. Depending on the configuration selected, a vacuum pump connected to the diverter may be activated or deactivated to draw fluid from the sampling interface, operation 312. Operation of the solvent pump may continue as required or desired for a particular application. For example, the solvent pump may operate for a predetermined time or until a predetermined volume of solvent is pumped therethough, to ensure complete filling of the associated flow path. In another example, operation 314, deactivating the solvent pump based at least in part on a signal received from a sensor such as a drip sensor associated with the sampling interface, may be performed. Performance of this optional operation may help prevent sample contamination, discharge of solvent into the sample chamber, or other undesirable conditions.EXAMPLE

[0041] The solvent delivery subsystem described generally in FIGS. 1-3 may be utilized with different types of sampling interfaces that utilize a flow of solvent in one or more processes. Flow rates, fluidic connections and flow paths, and solvents utilized may be modified as required or desired for a particular application. In the example described below, a diverter utilizing multiple diverters (e.g., an inlet diverter and an outlet diverter) and an OPI (among other specifics) is described, and is but one example of a solvent delivery subsystem for a sampling interface.

[0042] FIG. 4 is a schematic view of a solvent delivery system 400 for a sampling interface that, in this case, is an OPI 402. In the depicted system 400, the diverter 404 is a dualcomponent diverter having an inlet (or first) diverter 404a and an outlet (or second) diverter 404b. Both the inlet diverter 404a and outlet diverter 404b are multi-position valves such as a sample injection valve typically utilized in HPLC, and each include a number of ports (referenced as ports 1-6 in the inlet diverter 404a, and referenced as ports A-F in the outlet diverter 404b). Depending on direction of flow through a particular port, each port may also be referred to as an inlet or outlet. In FIG. 4, the inlet diverter 404a includes six ports 1-6, but only three ports (1, 2, and 6) are utilized. In alternative examples, the remaining ports may be utilized for other functions or remain unused. In examples, the remaining ports (3, 4, 5) may be used to couple the inlet diverter 404a to another solvent pump, or to fluidically couple an OPI 402 to a vacuum pump 412, with appropriate internal flow paths. Other possible connections and flow paths would be apparent to a person of skill in the art.

[0043] The OPI 402 is fluidically coupled to the outlet diverter 404b at an OPI port F. A solvent delivery subsystem 406 includes a wash solvent pump 406a that is fluidically coupled to the inlet diverter 404a at a wash solvent inlet 6. The wash solvent pump 406a is fluidically coupled to a wash solvent reservoir 408a. A solvent delivery subsystem 406 includes a carrier solvent pump 406b that is fluidically coupled to the inlet diverter 404a at a carrier solvent inlet 2. The carrier solvent pump 406d is fluidically coupled to a carrier solvent reservoir 408b. A single degasser 210 degasses both the wash and carrier solvent liquids.

[0044] A vacuum pump 412 is coupled to the outlet diverter 404b at a vacuum pump outlet E, and a vacuum check valve 414 may be installed on the vacuum line 416 between the vacuum pump outlet E and the vacuum pump 412. The vacuum pump 412 is connected to awaste container 418 via a vacuum pump discharge 420. The waste container 418 is also connected to the outlet diverter 404b via a waste line 422 connected to waste outlet B. A waste check valve 424 prevents discharge from the vacuum pump 412 from entering the outlet diverter 404b. Inlet diverter 404a and outlet diverter 404b are connected via a diverter connection line 429 that fluidically couples a first diverter outlet 1 with a second diverter inlet A. A controller and drip sensor are not depicted but may be utilized, for example, consistent with those components described in FIG. 2.

[0045] As with the more general configuration depicted in FIG. 2, various fluid conduits are depicted between components in FIGS. 4A-4D. Further, FIGS. 4A-4D depict configurable flow paths within each diverter 404a, 404b that are used to control and set the various flow path configurations between the various components. The elements and components described in FIGS. 4A-4D are described above with regard to FIG. 4 and are not necessarily described further. Additionally, in the context of FIGS. 4A-4D, certain components, such as the wash solvent pump 406a, the carrier solvent pump 406b, and the vacuum pump 412 may be activated (or enabled) or deactivated (or disabled), as those words are defined above. Paths of fluids (liquids and / or gases) in each configuration are depicted by arrows.

[0046] FIG. 4A is a schematic view of the solvent delivery system 400 of FIG. 4 in a carrier configuration. When the solvent delivery system 400 is configured such that the diverter 404 is in the carrier configuration, flow path 428 (including flow path 428a between ports 2 and 1, and flow path 428b between ports A and F) is created to fluidically couple the carrier solvent pump 406b to the OPI 402 via the diverter 404. The carrier solvent pump 406b is activated to deliver a carrier solvent from the carrier solvent reservoir 408b to the OPI 402. The vacuum pump 412 is disabled.

[0047] FIG. 4B is a schematic view of the solvent delivery system 400 of FIG. 4 in a flush configuration. When the solvent delivery system 400 is configured such that the diverter 404 is the flush configuration, flow path 432 is created between ports F and E to fluidically couple the OPI 402 to the vacuum pump 412 via the outlet diverter 404b. Both solvent pump 406a, 406b are disabled. The vacuum pump 412 is activated to generate a vacuum at the OPI 402 via the outlet diverter 404b and direct a discharge from the vacuum pump 412 to the waste line 422. The discharge may include any gas or liquid drawn from the OPI 402.

[0048] FIG. 4C is a schematic view of the solvent delivery system 400 of FIG. 4 in a prime configuration. When the solvent delivery system 400 is configured such that the diverter 404 is the prime configuration, flow path 430 is created to fluidically couple the carrier solvent pump 406b to the waste line 422 via the diverter 404. More particularly, depending on the solvent type to be delivered during the prime configuration, flow path 430b between ports A and B is created, along with either of flow path 430a between ports 6 and 1 and flow path 430c between ports 2 and 1. Depending on the solvent to be delivered, only one of the wash solvent pump 406a and the carrier solvent pump 406b is activated to deliver a wash solvent or a carrier solvent from the wash solvent reservoir 408a or the carrier solvent reservoir 408b to the waste line 422. Flow through both flow paths is depicted in FIGS. 4C for illustrative purposes. The vacuum pump 412 is disabled (although as noted above, the solvent delivery subsystem may be operated simultaneously in both the flush configuration and prime configuration if desired).

[0049] FIG. 4D is a schematic view of the solvent delivery system 400 of FIG. 4 in a wash configuration. When the solvent delivery system 400 is configured such that the diverter 404 is in the wash configuration, flow path 428 (including flow path 428c between ports 6 and 1, and flow path 428b between ports A and F) is created to fluidically couple the wash solvent pump 406a to the OPI 402 via the diverter 404. The wash solvent pump 406a is activated to deliver a wash solvent from the wash solvent reservoir 408a to the OPI 402. The vacuum pump 412 is disabled.

[0050] FIG. 5 depicts one example of a suitable operating environment 500 in which one or more of the present examples can be implemented. This operating environment may be incorporated directly into the controller for a mass spectrometry or other mass analysis system, e.g., such as the controller(s) depicted in FIGS. 1 or 2-2D and referenced with regard to FIGS. 4-4D. This is only one example of a suitable operating environment and is not intended to suggest any limitation as to the scope of use or functionality. Other well-known computing systems, environments, and / or configurations that can be suitable for use include, but are not limited to, personal computers, server computers, hand-held or laptop devices, multiprocessor systems, microprocessor-based systems, programmable consumer electronics such as smart phones, network PCs, minicomputers, mainframe computers, tablets, distributed computing environments that include any of the above systems or devices, and the like.

[0051] In its most basic configuration, operating environment 500 typically includes at least one processing unit 502 and memory 504. Depending on the exact configuration and type of computing device, memory 504 (storing, among other things, instructions to control the solvent pump(s), valve(s), vacuum pump, diverter(s) in response to sensor signals, user or program selections, etc., or perform other methods disclosed herein) can be volatile (such as RAM), non-volatile (such as ROM, flash memory, etc.), or some combination of the two. This most basic configuration is illustrated in FIG. 5 by dashed line 506. Further, environment 500 can also include storage devices (removable, 508, and / or non-removable, 510) including, but not limited to, magnetic or optical disks or tape. Similarly, environment 500 can also have input device(s) 514 such as touch screens, keyboard, mouse, pen, voice input, etc., and / or output device(s) 516 such as a display, speakers, printer, etc. Also included in the environment can be one or more communication connections 512, such as LAN, WAN, point to point, Bluetooth, RF, etc.

[0052] Operating environment 500 typically includes at least some form of computer readable media. Computer readable media can be any available media that can be accessed by processing unit 502 or other devices having the operating environment. By way of example, and not limitation, computer readable media can include computer storage media and communication media. Computer storage media includes volatile and nonvolatile, removable and non-removable media implemented in any method or technology for storage of information such as computer readable instructions, data structures, program modules or other data. Computer storage media includes, RAM, ROM, EEPROM, flash memory or other memory technology, CD-ROM, digital versatile disks (DVD) or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, solid state storage, or any other tangible medium which can be used to store the desired information. Communication media embodies computer readable instructions, data structures, program modules, or other data in a modulated data signal such as a carrier wave or other transport mechanism and includes any information delivery media. The term "modulated data signal" means a signal that has one or more of its characteristics set or changed in such a manner as to encode information in the signal. By way of example, and not limitation, communication media includes wired media such as a wired network or direct-wired connection, and wireless media such as acoustic, RF, infrared and other wireless media. Combinations of the any of the above should also be included within the scope of computerreadable media. A computer-readable device is a hardware device incorporating computer storage media.

[0053] The operating environment 500 can be a single computer operating in a networked environment using logical connections to one or more remote computers. The remote computer can be a personal computer, a server, a router, a network PC, a peer device or other common network node, and typically includes many or all of the elements described above as well as others not so mentioned. The logical connections can include any method supported by available communications media. Such networking environments are commonplace in offices, enterprise-wide computer networks, intranets and the Internet.

[0054] In some examples, the components described herein include such modules or instructions executable by computer system 500 that can be stored on computer storage medium and other tangible mediums and transmitted in communication media. Computer storage media includes volatile and non-volatile, removable and non- removable media implemented in any method or technology for storage of information such as computer readable instructions, data structures, program modules, or other data. Combinations of any of the above should also be included within the scope of readable media. In some examples, computer system 500 is part of a network that stores data in remote storage media for use by the computer system 500.

[0055] This disclosure described some examples of the present technology with reference to the accompanying drawings, in which only some of the possible examples were shown. Other aspects can, however, be embodied in many different forms and should not be construed as limited to the examples set forth herein. Rather, these examples were provided so that this disclosure was thorough and complete and fully conveyed the scope of the possible examples to those skilled in the art.

[0056] Although specific examples were described herein, the scope of the technology is not limited to those specific examples. One skilled in the art will recognize other examples or improvements that are within the scope of the present technology. Therefore, the specific structure, acts, or media are disclosed only as illustrative examples. Examples according to the technology may also combine elements or components of those that are disclosed in general but not expressly exemplified in combination, unless otherwise stated herein. The scope of the technology is defined by the following claims and any equivalents therein.

Claims

Claims1. A solvent delivery system for an open port interface (OPI), the solvent delivery system comprising: a first diverter comprising a wash solvent inlet, a carrier solvent inlet, and a first diverter outlet; a wash solvent pump fluidically coupled to the wash solvent inlet; a carrier solvent pump fluidically coupled to the carrier solvent inlet; and a second diverter comprising: a second diverter inlet fluidically coupled to the first diverter outlet; an OPI port configured to be coupled to an OPI; and a waste outlet configured to be coupled to a waste container.

2. The solvent delivery system of claim 1, wherein the second diverter further comprises a vacuum pump outlet and wherein the solvent delivery system further comprises a vacuum pump fluidically coupled to the vacuum pump outlet, wherein the vacuum pump outlet is selectively couplable to the OPI port via the second diverter and wherein the vacuum pump is configured to generate a vacuum on the OPI to draw liquid from the OPI and to a vacuum pump discharge.

3. The solvent delivery system of claim 2, further comprising a vacuum pump check valve disposed between the vacuum pump outlet and the vacuum pump.

4. The solvent delivery system of any of claims 1-3, further comprising a waste check valve disposed downstream of the waste outlet.

5. The solvent delivery system of any of claims 1-4, further comprising a controller for setting the solvent delivery system in a plurality of flow configurations, wherein the plurality of flow configurations comprise at least one of: a carrier configuration; a flush configuration; a prime configuration; and a wash configuration.

6. The solvent delivery system of claim 5, wherein when the controller sets the system to the carrier configuration: the carrier solvent pump is fluidically coupled to the OPI via the carrier solvent inlet, the first diverter outlet, and the second diverter inlet, and the OPI port; and the controller activates the carrier solvent pump to deliver a carrier solvent from a carrier solvent reservoir to the OPI.

7. The solvent delivery system of any of claims 5-6, further comprising: a vacuum pump fluidically coupled to the OPI via a vacuum pump outlet on the second diverter and the OPI port, and wherein when the controller sets the system to the flush configuration, the controller activates the vacuum pump to draw at least one of an air and a liquid from the OPI to the vacuum pump.

8. The solvent delivery system of any of claims 5-7, wherein when the controller sets the system to the prime configuration: only one of:(a) the carrier solvent pump is fluidically coupled to the waste container via the carrier solvent inlet, the first diverter outlet, and the second diverter inlet, and the waste outlet; and(b) the wash solvent pump is fluidically coupled to the waste container via the wash solvent inlet, the first diverter outlet, and the second diverter inlet, and the waste outlet; and the controller activates only one of the carrier solvent pump and the wash solvent pump to deliver only one of a carrier solvent and a wash solvent from only one of a carrier solvent reservoir and a wash solvent reservoir to the waste container.

9. The solvent delivery system of any of claims 5-8, wherein when the controller sets the system to the wash configuration: the wash solvent pump is fluidically coupled to the OPI via the wash solvent inlet, the first diverter outlet, and the second diverter inlet, and the OPI port; and the controller activates the wash solvent pump to deliver a wash solvent from a wash solvent reservoir to the OPI.

10. The solvent delivery system of claim 7, wherein the vacuum pump comprises a vacuum pump discharge fluidically coupled to the waste container.

11. The solvent delivery system of any of claims 5-10, wherein the controller is configured to set the system in the flush configuration and the prime configuration simultaneously.

12. A solvent delivery system for a sampling interface, the solvent delivery system comprising: a solvent pump subsystem; a diverter fluidically coupled to the solvent pump subsystem and to the sampling interface; a vacuum pump fluidically coupled to the diverter; a waste line fluidically coupled to each of the vacuum pump and the diverter; at least one controller operatively coupled to the solvent pump subsystem, the diverter, and the vacuum pump; and a memory coupled to the at least one controller, the memory storing instructions that, when executed by the controller, performs a set of operations comprising: setting the diverter in one of a plurality of flow configurations; and at least one of activating and disabling at least one of the solvent pump subsystem and the vacuum pump.

13. The solvent delivery system of claim 12, wherein the plurality of flow configurations comprise: a carrier configuration; a flush configuration; a prime configuration; and a wash configuration.

14. The solvent delivery system of claim 13, wherein when the controller sets the diverter in the carrier configuration, the set of operations further comprises: activating the solvent pump subsystem to deliver a carrier solvent to the sampling interface via the diverter; and disabling the vacuum pump.

15. The solvent delivery system of any of claims 13-14, wherein when the controller sets the diverter in the flush configuration, the set of operations further comprises: disabling the solvent pump subsystem; and activating the vacuum pump to generate a vacuum at the sampling interface via the diverter and direct a discharge from the vacuum pump to the waste line.

16. The solvent delivery system of any of claims 13-15, wherein when the controller sets the diverter in the prime configuration, the set of operations further comprises: activating the solvent pump subsystem to deliver at least one of a carrier solvent and a wash solvent to the waste line via the diverter; and disabling the vacuum pump.

17. The solvent delivery system of any of claims 13-16, wherein when the controller sets the diverter in the wash configuration, the set of operations further comprises: activating the solvent pump subsystem to deliver a wash solvent to the sampling interface via the diverter; and disabling the vacuum pump.

18. A method of operating a solvent delivery system for a sampling interface, the method comprising: receiving a configuration selection signal; and based at least in part on the configuration cycle selection signal: selecting a diverter flow path from a plurality of diverter flow paths of a diverter; sending a signal to the diverter to set the diverter in the selected diverter flow path; selecting a solvent; only one of activating and deactivating a solvent pump associated with the solvent, wherein the solvent pump is fluidically coupled to the diverter, wherein activation of the solvent pump delivers the selected solvent to the diverter; and only one of activating and deactivating a vacuum pump fluidically coupled to the diverter.

19. The method of claim 18, further comprising deactivating the solvent pump based at least in part on a signal received from a drip sensor associated with the sampling interface.

20. The method of any of claims 18-19, wherein the diverter comprises a pair of configurable diverters, wherein a first diverter of the pair of configurable diverters is fluidically coupled to the sampling interface, wherein a second diverter of the pair of configurable diverters is fluidically coupled to the vacuum pump, and wherein selecting a diverter flow path comprises changing an internal flow path of at least one of the first diverter and the second diverter.

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