Patent Description:
In one aspect, the technology relates to a method of performing liquid chromatography (LC) with an LC system including an LC column and an analyzer, the method including: delivering a transport liquid to an open port interface (OPI) of a sample receiving circuit, wherein the sample receiving circuit includes a sample transfer chamber; ejecting a sample from a sample holder into the OPI with a non-contact ejector; receiving the transport liquid and the sample in the sample transfer chamber; decoupling the sample transfer chamber from the sample receiving circuit; coupling the sample transfer chamber to an analysis circuit; delivering a solvent to the analysis circuit; pushing the sample from the sample transfer chamber with the solvent; passing the sample and the solvent through the LC column to produce an eluent; and analyzing the eluent with the analyzer. In an example, the sample is ejected into the OPI substantially simultaneously with delivering the transport liquid to the OPI. In another example, the method further includes aspirating a portion of the transport liquid from the sample transfer chamber substantially simultaneously with delivering the transport liquid to the OPI. In yet another example, the method further includes ejecting from a waste outlet the portion of the transport liquid aspirated from the sample transfer chamber. In still another example, delivering the transport liquid to the OPI includes pumping the transport liquid to the OPI at a first flow rate with a first pump.

In another example of the above aspect, aspirating the portion of the transport liquid from the sample transfer chamber includes aspirating the portion of the transport liquid at a second flow rate with a second pump. In an example, the first flow rate and the second flow rate are substantially similar. In another example, the method further includes, prior to decoupling the sample transfer chamber from the sample receiving circuit, terminating delivery of the transport liquid to the OPI and terminating ejection of the sample from the sample holder. In yet another example, the method further includes, prior to decoupling the sample transfer chamber from the sample receiving circuit, receiving a plurality of samples in the sample transfer chamber. In still another example, the method further includes during pushing of the sample, flushing the sample receiving circuit with a flushing liquid.

In another example of the above aspect, the transport liquid is substantially similar to the flushing liquid. In an example, flushing the sample receiving circuit includes operating a transport liquid pump and a waste pump. In another example, the method further includes, subsequent to pushing of the sample, recoupling the sample transfer chamber to the sample receiving circuit. In yet another example, the transport liquid and the solvent are different.

In another aspect, the technology relates to A liquid chromatography (LC) system including: an analysis circuit including a solvent pump and an LC column; an analyzer fluidically coupled to the LC column; a sample receiving circuit including a transport liquid pump and an open port interface (OPI) fluidically coupled to the transport liquid pump; a non-contact ejector configured to eject droplets from a sample holder into the OPI; and a sample transfer chamber selectively positionable in a first position and a second position, wherein in the first position, the sample transfer chamber is fluidically coupled to the sample receiving circuit, and wherein in the second position, the sample transfer chamber is fluidically coupled to the analysis circuit. In an example, the sample receiving circuit further includes a waste pump selectively fluidically couplable to the sample transfer chamber. In another example, the transport liquid pump is the waste pump. In yet another example, the sample transfer chamber is disposed within a six-port valve. In still another example, the analyzer includes a mass spectrometry device.

In another example of the above aspect, the non-contact ejector includes an acoustic droplet ejector.

HPLC separates analytes within a sample based on their different interaction with adsorbent material. In standard HPLC systems, a liquid sample is dissolved in a solvent (e.g., the mobile phase), and then flowed through a device (e.g., a liquid chromatography (LC) column) containing a stationary phase. The analytes with stronger retention to the stationary phase will take longer to travel through the LC column, thus causing separation of the sample. The target analytes of the separated sample may then be delivered to a detector for analysis, as described herein. Pressure from the HPLC system may be used to initiate a controlled flow of an eluent of the separated sample and the solvent through the LC column and towards the detector. HPLC systems can utilize different buffers or solvents, including those that have high conductivity.

<FIG> is a schematic depiction of an HPLC system <NUM>. The components of such systems are very well known in the art, but are described here to provide further context to the disclosure. The HPLC system <NUM> includes one or more solvent reservoirs <NUM> that contain solvent(s) to be used as a moving fluid stream (the so-called "mobile phase"). A variety of solvents that may be utilized and are well-known in the art. The solvent(s) are drawn from the one or more reservoirs <NUM> by a solvent delivery system in the form of a high-pressure liquid chromatography pump <NUM>. Samples are then delivered to the mobile phase at an autosampler <NUM>, which injects the samples into the solvent. Relevant to the present application, an open port interface (OPI), in conjunction with a non-contact ejection system, may be utilized as the autosampler <NUM>. Both the OPI and details regarding incorporation thereof into various HPLC systems are described below. Discrete samples are then carried by the mobile phase to the head of a chromatographic column <NUM>. The mobile phase and injected samples enter the column <NUM> and pass through a particle bed therein. The particle bed separates the sample into individual analyte bands. The separated mixture passes to a detector <NUM>, which may be a mass analysis device such as a mass spectrometry (MS) detector, or other type of detector, as described herein. A controller in the form of a computer <NUM> may be used to process, analyze, display, etc., the results received from the detector <NUM>, as well as control the various other components within the HPLC system <NUM>. Thus, sample compounds that include multiple analytes that otherwise could not be distinguished from one another by standard MS systems may have those analytes first separated in an LC column, prior to introduction, analysis, and identification in the MS system.

The HPLC systems described herein utilize an OPI in conjunction with a non-contact sampling device, as the autosampler (depicted in <FIG> as element <NUM>) to introduce samples to an HPLC system. In examples, the non-contact sampling device may be an acoustic droplet ejector (ADE) or a pressure-based ejector, or a pressure-based droplet dispenser. Use of a non-contact sampling device in conjunction with an OPI has a number of advantages. For example, such systems typically allow for rapid ejection of samples from a well plate or other sample holder. Cross-contamination between individual wells or sample holders can also be reduced or eliminated by eliminating the physical structure, such as a pipette, used to draw samples from individual wells. Since such pipettes must be cleaned between wells, elimination of such physical elements can drastically increase system throughput and reduce solvent waste. Further, with the configurations depicted herein, only select samples contained in a well plate need be subject to a complete LC analysis, which also reduces total time typically required to analyze all the samples of a well plate.

<FIG> depicts a schematic view of such an autosampler <NUM>, including both a non-contact sampling device <NUM> and an OPI sampling interface <NUM>. In examples, the non-contact sampling device <NUM> may be an ADE or a pressure-based droplet ejector, as described elsewhere herein. The ADE <NUM> includes an acoustic ejector <NUM> that is configured to eject a droplet <NUM> from a reservoir or well <NUM> of a well plate <NUM> into the open end of sampling OPI <NUM>. A liquid handling system <NUM> (e.g., including one or more pumps <NUM>) provides for the flow of liquid from a transport liquid reservoir <NUM>. The transport liquid may be aspirated out of the OPI <NUM>, along with a liquid sample, as described elsewhere herein. The transport liquid reservoir <NUM> (e.g., containing a liquid desorption solvent) can be fluidically coupled to the sampling OPI <NUM> via a supply conduit <NUM> through which the transport liquid can be delivered at a selected volumetric rate by the pump <NUM> (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), all by way of non-limiting example. As discussed in detail below, the flow of liquid into and out of the sampling OPI <NUM> occurs within a sample space accessible at the open end such that one or more droplets <NUM> can be introduced into the transport liquid boundary <NUM>.

The ADE <NUM> is configured to generate acoustic energy that is applied to a liquid contained within a reservoir <NUM> that causes one or more droplets <NUM> to be ejected from the reservoir <NUM> into the open end of the sampling OPI <NUM>. A controller <NUM> can be operatively coupled to and can be configured to operate any aspect of the autosampler <NUM>. Controller <NUM> 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. In examples, the controller <NUM> may be the controller of the HPLC system depicted in <FIG>. Wired or wireless connections between the controller <NUM> and the remaining elements of the autosampler <NUM> are not depicted but would be apparent to a person of skill in the art.

The liquid discharged may include discrete volumes of liquid samples LS received from each reservoir <NUM> of the well plate <NUM>. The discrete volumes of liquid samples LS are typically separated from each other by volumes of the transport liquid S as they are aspirated through a conduit <NUM>. In conjunction with the HPLC system depicted generally in <FIG>, devices for aspirating the sample and transport liquid are described in more detail below.

<FIG> depicts a mass analysis system <NUM> such as a mass spectrometry (MS) system that is for ionizing and mass analyzing analytes received from the HPLC system. Such a system <NUM> is described, for example, in <CIT>. As shown in <FIG>, the example MS <NUM> generally includes the an ESI source <NUM> for discharging a liquid containing one or more sample analytes (e.g., via electrospray electrode <NUM>) into an ionization chamber <NUM>, and a mass analyzer detector (depicted generally at <NUM>) in communication with the ionization chamber <NUM> for downstream processing and/or detection of ions generated by the ESI source <NUM>. Due to the configuration of the nebulizer probe <NUM> and electrospray electrode <NUM> of the ESI source <NUM>, samples ejected therefrom are transformed into the gas phase. The ESI source <NUM> can include a source <NUM> of pressurized gas (e.g. nitrogen, air, or a noble gas) that supplies a high velocity nebulizing gas flow to the nebulizer probe <NUM> that surrounds the outlet end of the electrospray electrode <NUM>. As depicted, the electrospray electrode <NUM> protrudes from a distal end of the nebulizer probe <NUM>. The nebulizing gas flow interacts with the liquid discharged from the electrospray electrode <NUM> to enhance the formation of the sample plume and the ion release within the plume for sampling by mass analyzer detector <NUM>, e.g., via the interaction of the high speed nebulizing flow and jet of liquid sample (e.g., analyte-solvent dilution). The nebulizer gas can be supplied at a variety of flow rates, for example, in a range from about <NUM>/min to about <NUM>/min, which can also be controlled under the influence of controller <NUM> (e.g., via opening and/or closing valve <NUM>). In examples, a controller <NUM> may be the controller of the HPLC system depicted in <FIG>.

It will also be appreciated by a person skilled in the art and in light of the teachings herein that the mass analyzer detector <NUM> can have a variety of configurations. Generally, the mass analyzer detector <NUM> is configured to process (e.g., filter, sort, dissociate, detect, etc.) sample ions generated by the ESI source <NUM>. By way of non-limiting example, the mass analyzer detector <NUM> 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 non-limiting, 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 "<NPL>); and <CIT>, entitled "Collision Cell for Mass Spectrometer". Other detectors, such as UV-vis absorbance detectors, charged aerosol detectors (CAD), refractive index detectors, photodiode array detectors (PDA), inductively-coupled plasma mass spectrometry detectors, (ICP-MS), or fluorescence detectors, may also be utilized.

Other detectors, 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 HPLC systems described herein. For instance, other suitable systems that may be utilized in conjunction with the HPLC systems described herein 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 <NUM> including, for example, an ion mobility spectrometer (e.g., a differential mobility spectrometer (DMS)) that is disposed between the ionization chamber <NUM> and the mass analyzer detector <NUM> and is configured to separate ions based on their mobility difference under high-field and low-field conditions. Additionally, it will be appreciated that the mass analyzer detector <NUM> can comprise a detector that can detect the ions that pass through the analyzer detector <NUM> and can, for example, supply a signal indicative of the number of ions per second that are detected.

The subsystems depicted above in <FIG> can be combined in various configurations to produce HPLC systems that benefit from non-contact ejection, high throughput analysis, and other performance advantages that will be apparent to a person of skill in the art upon reading the following disclosure. The described subsystems may be integrated into a single HPLC system in accordance with the examples depicted herein, and other configurations. Such systems may utilize a plurality of individually-controlled valves, pumps, moveable well plate stages, OPIs, ADEs, etc., to move samples though various configurations of liquid flow paths. The flow paths may be full-scale or may be on a microfluidic scale.

<FIG> depict an HPLC system <NUM> utilizing a non-contact sampling device <NUM> and an OPI sampling interface <NUM>. The components depicted in <FIG> are described concurrently, followed by a description of the operation of the HPLC system <NUM>. The non-contact sampling device <NUM> ejects a sample droplet <NUM> from a well tray <NUM>. A low-pressure transport liquid pump <NUM> delivers transport liquid to the OPI <NUM>, as described elsewhere herein. A low-pressure waste pump or aspirator <NUM> provides the aspiration pressure to draw the transport liquid and sample droplet <NUM> through the sample receiving circuit <NUM> of the system <NUM>. The transport liquid and sample droplet <NUM> are drawn through a valve <NUM> (described below) and ultimately ejected to a waste container <NUM>. An LC analysis circuit <NUM> of the system <NUM> includes a high-pressure solvent pump <NUM> (also referred to as an HPLC pump) that delivers solvent through the valve <NUM> and onward through the LC column <NUM> and to a detector <NUM>. The valve <NUM> selectively connects parts thereof to the sample receiving circuit <NUM> or the LC analysis circuit <NUM>. The valve <NUM> includes a sample transfer chamber <NUM> and a bypass channel <NUM>, as well as a number of ports, identified in <FIG> as ports <NUM>-<NUM>. These may be selectively coupled to connections on the sample receiving circuit <NUM> (connections A and B) and connections on the analysis circuit <NUM> (connections C and D). A first method of operation of the system <NUM> will now be described.

There are numerous ways to connect tubing and valves to accomplish this. One such example, beginning with <FIG>, the valve <NUM> is in a first position, where ports <NUM>- <NUM>, <NUM>-<NUM>, and <NUM>-<NUM> are fluidically coupled via a dedicated rotor channel. In this first position, tubing A and B are fluidically coupled as follows: tubing A to port <NUM> through the valve rotor channel, port <NUM> through the sample transfer chamber <NUM> to port <NUM>, port <NUM> through the valve rotor channel to port <NUM>, port <NUM> to tubing B of the sample receiving circuit <NUM>. This leaves, ports <NUM> and <NUM> coupled to tubing C and D, respectively, of the LC analysis circuit <NUM>. The rotor channel between ports <NUM> and <NUM> functions as a bypass channel <NUM>. Transport liquid is delivered to the sample receiving circuit <NUM> by the transport liquid pump <NUM>. The waste pump or aspirator <NUM> is operated simultaneously at a substantially similar or the same flow rate, thereby drawing a flow of transport liquid through the sample receiving circuit <NUM>, as well as preventing overflow at the OPI <NUM>. A sample is introduced to the OPI <NUM> in the form of a droplet <NUM> ejected with the non-contact ejector <NUM>. The various functions of the sample receiving circuit <NUM> may be performed substantially simultaneously with those of the LC analysis circuit <NUM>, but this is not required. In the LC analysis circuit <NUM>, solvent may be pushed through the LC column <NUM> towards the detector <NUM>, but this is not required. In fact, it may be desirable to maintain only a minimal flow through the LC analysis circuit <NUM>, to prevent undesirable waste of the solvent. In <FIG>, the liquid sample droplet <NUM> is transported, via the aspirated transport liquid, towards the valve <NUM>, until it is ultimately received in the sample transfer chamber <NUM>, as depicted in <FIG>. Since the flow rate of the waste pump <NUM> is known, along with the tubing volume, the time required for the droplet <NUM> to travel from the OPI <NUM> to the sample transfer chamber <NUM> is known and may be timed appropriately. At this time, flow of transport liquid into the OPI <NUM> is terminated, as is aspiration of the transport liquid and sample <NUM> through the sample receiving circuit <NUM> (e.g., operation of the transport liquid pump <NUM> and the waste pump <NUM> ceases). Thereafter, as depicted in <FIG>, the valve <NUM> is positioned in a second position, where ports <NUM>-<NUM>, <NUM>-<NUM>, and <NUM>-<NUM> are fluidically coupled. In this second position, tubing A and B are fluidically coupled directly through the bypass channel <NUM>. Tubing C and D are fluidically coupled as follows: tubing C to port <NUM> through the rotor channel, port <NUM> to port <NUM> through the rotor channel, port <NUM> through the sample transfer chamber <NUM> to port <NUM>, port <NUM> through the rotor channel to port <NUM>, and port <NUM> to tubing D of the LC analysis circuit <NUM>. This fluidically couples the sample transfer chamber <NUM> to the LC analysis circuit <NUM>, where the HPLC pump <NUM> may then push the sample <NUM> through the LC column <NUM>. An eluent of the separated sample and the solvent exits the LC column <NUM> and is pushed on to the detector <NUM>. Since ports <NUM> and <NUM> are presently fluidically coupled to connections A and B of the sample receiving circuit <NUM>, respectively, the solvent contained within bypass channel <NUM> of the valve <NUM> may be flushed from the system <NUM> by operation of the waste pump <NUM>.

Another method <NUM> of operating an LC system utilizing an OPI and a non-contact ejector is depicted in <FIG>. This method <NUM> may be performed with the HPLC system depicted, for example, in <FIG>, above. The method <NUM> begins with operation <NUM>, delivering a transport liquid to the OPI of a sample receiving circuit. The sample receiving circuit includes a sample transfer chamber of a valve in fluidic communication therewith. Examples of such valves containing a sample transfer chamber are depicted in <FIG> above, and elsewhere herein. As the transport liquid is delivered by the transport liquid pump, the sample receiving circuit, including the sample transfer chamber, fills with the transport fluid. In order to maintain desirable flow conditions within the OPI, a portion of the transport liquid introduced to the sample transfer chamber is aspirated therefrom, for example, by operation of the waste pump. In examples, the waste pump may operate at a volumetric flow rate substantially similar to that of the transport liquid pump. In other examples, however, the volumetric flow rate of the waste pump may be slightly greater than that of the transport liquid pump to ensure, so as to more clearly prevent an overflow condition, which may occur when a larger sample volume is introduced to the OPI. Regardless, appropriate volumetric flow rates to and from an OPI to prevent overflow thereof are known.

Operation <NUM> includes ejecting a sample droplet from a sample holder into the OPI with a non-contact ejector. In examples, operations <NUM> and <NUM> may be performed substantially simultaneously, as depicted by dashed box <NUM>. Operation <NUM> includes receiving the transport liquid and the sample in the sample transfer chamber. Once in the sample transfer chamber, the sample is ready to be introduced to the LC analysis circuit. Prior to performing the introduction, however, operation of the transport liquid pump and the waste pump is terminated, thereby ceasing flow of transport liquid through the sample receiving circuit. With transport liquid flow terminated, ejections of samples also cease. In operation <NUM>, the sample transfer chamber is decoupled from the sample receiving circuit. Thereafter, the sample transfer chamber is coupled to an analysis circuit of the LC system, operation <NUM>. In the context of the system depicted in <FIG>, operations <NUM> and <NUM> contemplate rotating, adjusting, or otherwise actuating a valve to change the circuit to which the sample transfer chamber is coupled. In other examples, one or more gate valves may be opened or closed (or multi-position valves may be actuated) so as to connect the sample transfer chamber to the desired circuit. With the sample receiving chamber now fluidically coupled to the LC analysis circuit, operation <NUM>, delivering a solvent to the LC analysis circuit, is performed, e.g., with an HPLC pump. This delivery of solvent pushes the sample from the sample transfer chamber, operation <NUM>. Continued pressure applied by the HPLC pump passes the sample and the solvent through the LC column to produce an eluent, operation <NUM>. This eluent is then forced downstream to be analyzed with an analyzer in operation <NUM>. During or after this analysis is performed in the LC analysis circuit, transport liquid flow may recommence in the sample receiving circuit, which is once again complete due to the position of the bypass, as depicted in <FIG>. This transport liquid flow may flush any solvent present in the bypass to a waste station. Also, any samples that may be present in the sample receiving circuit may also be flushed. This may be desirable under circumstances where, after analysis of a number of samples are performed successfully, any remaining untested samples may be flushed from the system without testing. Upon completion of any desired analyzing or flushing operations, the sample transfer chamber may be recoupled to the sample receiving circuit for introduction of additional sample(s) for testing.

<FIG> depicts a HPLC system <NUM> for processing multiple ejected sample droplets <NUM>. In general, elements or components beginning with the number <NUM> in <FIG> and <FIG> correspond to elements or components beginning with the number <NUM> in <FIG>. As such, not every element or component is necessarily described again with regard to <FIG> and <FIG>. The system <NUM> depicts a plurality of sample droplets <NUM> ejected from a well plate <NUM> with a non-contact ejector <NUM>. The samples <NUM> may be multiple ejections from a single well or may be a single ejection from each well of the well plate <NUM>. The ejected samples <NUM> stack along the inlet side <NUM> of the sample receiving circuit <NUM> towards the valve <NUM>. In <FIG>, the valve <NUM> is depicted in the first position, as described above with regard to <FIG>. In this first position, flow of the samples <NUM> and the transport fluid passes into the sample transfer chamber <NUM>, where, again, the sample droplets <NUM> remain stacked for transfer to the analysis circuit <NUM>. On the outlet side <NUM> of the sample receiving circuit <NUM>, untested samples <NUM> may be aspirated by waste pump <NUM> towards a waste container <NUM>. During this time, solvent flow from the HPLC pump <NUM> may pass through the bypass <NUM>, since it is generally desirable to maintain some solvent flow through the LC column <NUM>. Flow of transport fluid into and out of the OPI <NUM> may cease by terminating operation of the transport liquid pump <NUM> and the waste pump <NUM>, and flow of solvent may cease by terminating operation of the HPLC pump <NUM>. Thereafter, the valve <NUM> may be moved to the second position, as depicted in <FIG>, and as described above in the context of <FIG>. Solvent delivered by the HPLC pump <NUM> forces the samples <NUM> through the column <NUM>, from which an eluent flows to the analyzer <NUM>. Prior to the valve <NUM> returning to the first position, transport liquid flow generated by the transport liquid pump <NUM> and waste pump <NUM> may be used to flush the sample receiving circuit <NUM>. This is due to the position of the bypass <NUM> relative to connections A and B of the sample receiving circuit <NUM>. The transport liquid may be used as the flushing liquid or another liquid may be introduced via a supplemental port downstream of the OPI <NUM>. Flushing operations may be performed substantially simultaneously with the passing of samples <NUM> through the column <NUM> and/or introduction to the analyzer <NUM>.

The system configuration depicted in <FIG> and <FIG> may be further modified, as required or desired, for particular applications. <FIG> depict a number of different systems. In each, elements or components beginning with the numbers <NUM> to <NUM> in <FIG> correspond to elements or components beginning with the number <NUM> in <FIG>. As such, not every element or component is necessarily described again with regard to <FIG>. Distinguishing elements or components, functions, operations, etc., are described. Methods of using such systems are also described and would be apparent to a person of skill in the art.

In <FIG>, the depicted system <NUM> includes two sample introduction stations, identified as SI-a and SI-b. Each station includes an OPI <NUM>, a transport liquid pump <NUM>, and a non-contact ejector <NUM>. Two well plates <NUM> and ejected droplets <NUM> are also depicted. In operation, sample introduction station SI-b introduces samples 706b as described above in the context of <FIG> and <FIG>. Sample introduction station SI-a, however, is directly connected (meaning, without an intervening valve <NUM> and LC analysis circuit <NUM>), to the analyzer <NUM>. Thus, samples 706a introduced at sample introduction station SI-a may be analyzed consistent with known analysis systems, without an intervening LC analysis process. In that case, aspiration force driving the fluid transfer from the OPI 704a is from the nebulizer gas being discharged from an ESI electrode such as depicted in the system depicted in <FIG>. In examples, well plates 708a and 708b may be the same well plate. First, sample droplets 706a from the well plate <NUM> may be ejected from sample introduction station SI-a for analysis by the analyzer <NUM>. If required or desired based on the results obtained, the well plate <NUM> may be moved to sample introduction station SI-b, where the sample droplets 706b may be ejected and analyzed as described elsewhere herein. This may be particularly useful for samples that include large-scale compounds, which may first be introduced in sample introduction station SI-a and directly analyzed by the analyzer <NUM>. Compound samples that require an additional analysis that would benefit from LC separation may then be introduced via sample introduction station SI-b and processed as described above. Thus, in a well tray having a significant number of sample wells, not every sample in every sample well need be subjected to the lengthy process time required for LC analysis, allowing for additional time savings.

<FIG> is similar to the system <NUM> depicted in <FIG>, but without a sample introduction station directly connected to the analyzer <NUM>. Instead, a single sample introduction station, with a dedicated OPI <NUM>, non-contact ejector <NUM>, and transport liquid pump <NUM> is utilized. The system includes a circuit selection valve <NUM> that selectively connects the sample receiving circuit <NUM> to either the valve <NUM> for connection to the LC analysis circuit <NUM> or a direct analysis circuit <NUM>. The direct analysis circuit <NUM> is connected to the analyzer <NUM>, where the electrospray electrode (element <NUM>, <FIG>) aspirates the transport liquid and sample droplets <NUM> for analysis. As described above with regard to <FIG>, this may be useful for first screening large scale compounds, then passing select compounds for further LC-based separation. Thereafter, the circuit selection valve <NUM> may disconnect or decouple the sample receiving circuit <NUM> from the analyzer <NUM> and the waste pump <NUM> may be activated to aspirate the sample droplets <NUM> and transport liquid into the valve <NUM>. LC analysis thereof may then be performed as described above in <FIG> and 6A-6B.

<FIG> depicts a system <NUM> that utilizes a single pump <NUM> (e.g., a peristaltic pump) that both delivers transport liquid (via delivery circuit <NUM>) to the OPI <NUM> via the sample receiving circuit <NUM>, as well as aspirates the transport liquid and sample droplet <NUM> through the valve <NUM> and towards the waste container <NUM>, via a waste circuit <NUM>. Instead of an integral transport liquid pump and reservoir as depicted elsewhere herein, a discrete transport liquid reservoir <NUM> is utilized as a source of the transport liquid. Since the peristaltic pump <NUM> produces a balanced flow in both the delivery circuit <NUM> and the waste circuit <NUM>, control to ensure balanced flow at the OPI <NUM> is simplified.

<FIG> depicts another system <NUM> that, in this example, utilizes a HPLC pump <NUM> to deliver solvent to both the LC analysis circuit <NUM> and the sample receiving circuit <NUM>. A valve <NUM> controls the flow therefrom and may be configured to divert only a minimal amount of solvent from the LC analysis circuit <NUM>, so as to not starve the LC column <NUM>. In this example, the solvent acts as the transport liquid prior to introduction of the solvent and sample droplets <NUM> to the LC analysis circuit <NUM>.

<FIG> depicts one example of a suitable operating environment <NUM> in which one or more of the present examples can be implemented. This operating environment may be incorporated directly into the controller for a system, e.g., such as the controllers depicted in <FIG> that control operation of the various components of the analysis system. 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.

In its most basic configuration, operating environment <NUM> typically includes at least one processing unit <NUM> and memory <NUM>. Depending on the exact configuration and type of computing device, memory <NUM> (storing, among other things, instructions to control the non-contact ejection device, position of the valve(s), activation of the various pumps, 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> by dashed line <NUM>. Further, environment <NUM> can also include storage devices (removable, <NUM>, and/or non-removable, <NUM>) including, but not limited to, magnetic or optical disks or tape. Similarly, environment <NUM> can also have input device(s) <NUM> such as touch screens, keyboard, mouse, pen, voice input, etc., and/or output device(s) <NUM> such as a display, speakers, printer, etc. Also included in the environment can be one or more communication connections <NUM>, such as LAN, WAN, point to point, Bluetooth, RF, etc..

Operating environment <NUM> 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 <NUM> 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. 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 computer readable media. A computer-readable device is a hardware device incorporating computer storage media.

The operating environment <NUM> 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.

In some examples, the components described herein include such modules or instructions executable by computer system <NUM> 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 <NUM> is part of a network that stores data in remote storage media for use by the computer system <NUM>.

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.

Claim 1:
A method of performing liquid chromatography, LC, with an LC system (<NUM>) comprising an LC column (<NUM>) and an analyzer (<NUM>), the method comprising:
delivering a transport liquid to an open port interface, OPI (<NUM>), of a sample receiving circuit (<NUM>), wherein the sample receiving circuit comprises a sample transfer chamber (<NUM>);
ejecting a sample from a sample holder into the OPI with a non-contact ejector (<NUM>);
receiving the transport liquid and the sample in the sample transfer chamber;
decoupling the sample transfer chamber from the sample receiving circuit;
coupling the sample transfer chamber to an analysis circuit (<NUM>);
delivering a solvent to the analysis circuit;
pushing the sample from the sample transfer chamber with the solvent;
passing the sample and the solvent through the LC column to produce an eluent; and
analyzing the eluent with the analyzer.