Patent ID: 12235248

The illustration in the drawing is schematic.

DETAILED DESCRIPTION

Before describing the figures in further detail, some basic considerations of the present invention will be summarized based on which exemplary embodiments have been developed.

According to an exemplary embodiment of the invention, a feed injection architecture of injecting a fluidic sample towards a separation unit is provided. In such a feed injection operation, it is possible to eject the fluidic sample into the main path (or flow path) without letting flow through the metering path. Thus, by feed injection, the fluidic sample may be fed into the main path, in particular while there remains a direct fluidic connection between a fluid drive and a mobile phase drive on the one hand and the separation unit on the other hand. Within the injector configuration according to an exemplary embodiment of the invention, the sample drive or metering device can be flushed in a bypass position with an optional external pump to reduce carryover. In an embodiment, it is also possible that the feed injection can be correlated with pump flow. Moreover, feed injection can be done continuously to dilute the fluidic sample with the main pass flow, i.e. with mobile phase driven by the fluid drive. In an embodiment, it is possible that the characteristics (in particular the speed, a dilution, etc.) of the feed injection can be adjusted dependent on method (in particular chromatographic method) requirements. Usage of a variable loop for different injection volumes is possible according to an exemplary embodiment of the invention.

In order to design an injector and in particular a fluidic valve of an injector according to an exemplary embodiment of the invention, it is possible to provide only one single high pressure valve with a corresponding stator/rotor design. In an embodiment, it is possible to calculate a compress/decompress volume. Moreover there is the possibility to measure pressure with an additional pressure sensor in-line or differentially to determine a compress/decompress volume.

The usage of such a setup according to an exemplary embodiment provides a hydraulic injection function with the capability to compress and/or decompress loop and/or needle and/or seat with the fluid drive or metering device before and/or after switching into and/or out of the flow path.

Furthermore the sample drive or metering device may be purgable with fresh solvent provided by an additional flush pump. Hence, the metering device may be purgable with the flush pump installed in the sampler.

With the described injector design, feed injection is possible. The described architecture is independent on solvents used in the analytical flow path. It is possible that the sample can be introduced with marginal influence of solvent used for the dilution of the fluidic sample. Both flow paths (i.e. needle, loop as sample accommodation volume, seat, metering device as sample drive, versus main path, analytical pump as fluid drive, column as separation unit) can work independently, except during the injection of fluidic sample. Therefore, the solvents used in both paths can be different.

Exemplary embodiments of the invention have several advantages. In order to exclude the needle, seat, loop and metering device from the main path of the analytical instrument, this setup can be used. The fluidic sample may be injected with a plunger movement of the metering device or a pre-generated overpressure (for providing an injection force for injecting a predefined amount of fluidic sample depending on the overpressure into the flow path) in the path of needle, seat, loop and metering device. The injection speed may be adjustable and can be set as method parameter. Moreover, dilution of the fluidic sample depending on an injection mode (feed to analytical flow) and metering device plunger movement is possible in a feed mode. Both an additional flow (through the plunger movement of the metering device) to the main path flow and a correlated flow, flow of plunger movement of the metering device are possible. A compressible and decompressible path of needle, seat, loop and metering device can be implemented. In an embodiment, there are only marginal pressure fluctuations due to injection due to sample path pre-compression. Multiple feed injections with one draw may be possible in one embodiment. High frequent injections may be possible as well, for instance for reaction monitoring. For example, a reaction can take place in the loop and can be fed partially into the mainpass just by switching and plunger movement of the metering device. A further advantage is a low carryover due to a purge position in which also the needle can be lifted to clean the needle seat interface (with solvent pumped from a flush pump). In an embodiment, the injection volume may be selectable. This is not limited, for example selectable in a range of maximum volume of the loop installed. The described injector architecture is pressure stable over a broad range of pressures, for instance up to 1300 bar. Moreover, the described injector architecture is usable for many applications, for instance for supercritical fluid chromatography.

Referring now in greater detail to the drawings,FIG.1depicts a general schematic of a liquid separation system as example for a sample separation apparatus10according to an exemplary embodiment of the invention. A pump as fluid drive20receives a mobile phase from a solvent supply25, typically via a degasser27, which degases and thus reduces the amount of dissolved gases in the mobile phase. The mobile phase drive or fluid drive20drives the mobile phase through a separation unit30(such as a chromatographic column) comprising a stationary phase. A sampler or injector40, implementing a fluidic valve95, can be provided between the fluid drive20and the separation unit30in order to subject or add (often referred to as sample introduction) a sample fluid into the mobile phase. The stationary phase of the separation unit30is configured for separating compounds of the sample liquid. A detector50is provided for detecting separated compounds of the sample fluid. A fractionating unit60can be provided for outputting separated compounds of sample fluid.

While the mobile phase can be comprised of one solvent only, it may also be mixed from plural solvents. Such mixing might be a low pressure mixing and provided upstream of the fluid drive20, so that the fluid drive20already receives and pumps the mixed solvents as the mobile phase. Alternatively, the fluid drive20might be comprised of plural individual pumping units, with plural of the pumping units each receiving and pumping a different solvent or mixture, so that the mixing of the mobile phase (as received by the separation unit30) occurs at high pressure and downstream of the fluid drive20(or as part thereof). The composition (mixture) of the mobile phase may be kept constant over time, the so called isocratic mode, or varied over time, the so called gradient mode.

A data processing unit or control unit70, which can be a PC or workstation, may be coupled (as indicated by the dotted arrows) to one or more of the devices in the sample separation apparatus10in order to receive information and/or control operation. For example, the control unit70may control operation of the control unit20(e.g. setting control parameters) and receive therefrom information regarding the actual working conditions (such as output pressure, etc. at an outlet of the pump20). The control unit70may also control operation of the solvent supply25(e.g. setting the solvent/s or solvent mixture to be supplied) and/or the degasser27(e.g. setting control parameters such as vacuum level) and might receive therefrom information regarding the actual working conditions (such as solvent composition supplied over time, vacuum level, etc.). The control unit70might further control operation of the sampling unit or injector40(e.g. controlling sample injection or synchronization of sample injection with operating conditions of the fluid drive20). The separation unit30might also be controlled by the control unit70(e.g. selecting a specific flow path or column, setting operation temperature, etc.), and send—in return—information (e.g. operating conditions) to the control unit70. Accordingly, the detector50might be controlled by the control unit70(e.g. with respect to spectral or wavelength settings, setting time constants, start/stop data acquisition), and send information (e.g. about the detected sample compounds) to the control unit70. The control unit70might also control operation of the fractionating unit60(e.g. in conjunction with data received from the detector50) and provide data back.

As illustrated schematically inFIG.1, the fluidic valve95can be brought into a switching state in which a fluidic T-piece (see reference numeral108) is formed within the fluidic valve95, thereby fluidically coupling the fluid drive20, the separation unit30, and a sample accommodation volume (compare vertical arrow inFIG.1) of the injector40in the shown injection switching state.

FIG.2toFIG.5illustrate an injector40according to an exemplary embodiment of the invention in different switching states.

The injector40according toFIG.2toFIG.5is configured for injecting a fluidic (here: liquid) sample into a flow path104between high pressure fluid drive20(configured for pumping mobile phase, i.e. a definable solvent composition) and separation unit30, embodied as a chromatographic column. For the purpose of separating the fluidic sample into fractions, the injector40comprises a sample loop or sample accommodation volume100for accommodating a certain amount of the fluidic sample prior to injecting. A sample drive102, which can be embodied as a metering pump or syringe pump, is configured for driving the fluidic sample from the sample accommodation volume100into the flow path104, when fluidic valve95is switched into a corresponding switching state (seeFIG.4). For driving the fluidic sample towards the separation unit30, a piston188of the sample drive102is controlled to move forwardly. Sample drive102is further configured for intaking fluidic sample from a sample container (not shown) into the sample accommodation volume100by a backward motion of the piston188. The fluidic valve95can be switched in multiple switching states under control of control unit70(seeFIG.2toFIG.5). By switching the fluidic valve95, it is possible to selectively couple the sample accommodation volume100with the flow path104(see for instanceFIG.4) or decouple the sample accommodation volume100from the flow path104(see for instanceFIG.2orFIG.3). The control unit70may be configured for adjusting an outlet pressure value and/or an outlet volumetric flow rate value (alternatively an outlet mass flow rate value) according to which the mixture between mobile phase and fluidic sample is driven to the separation unit30. In addition to the adjustment of the absolute amount of supplied fluid for time, the control unit70may simultaneously adjust the relative mixing ratio between mobile phase and fluidic sample.

The fluidic valve95is a rotatable fluidic valve95having a rotor and a stator being rotatable relative to one another so as to bring different fluid ports1-6of the stator in alignment with respective fluidic conduits110in the rotor. As indicated with reference numeral155inFIG.2toFIG.5, part of the fluidic conduits110may be embodied as stator grooves, whereas the rest of the fluid conduits110(not being indicated with reference numeral155) are embodied as rotor grooves according toFIG.2toFIG.5. This is shown in further detail inFIG.6A,FIG.6B. The fluidic valve95is an active fluidic valve being switchable under control of control unit70of the injector40.

The injector40comprises a needle112and a seat114configured for accommodating the needle112. Although not shown in the figures, the needle112is drivable towards a sample container (not shown) for intaking fluidic sample stored in the sample container into the sample accommodation volume100by the sample drive102. The needle112is furthermore configured to be drivable back to the seat114(as shown inFIG.2toFIG.5) prior to injection.

Reference numeral166indicates a waste.

Referring toFIG.2, a purge position of the fluidic valve95of the injector40is shown. According toFIG.2, the fluid drive20or analytical pump is fluidically connected to separation unit30embodied as liquid chromatography column. In the shown purge position, loop or sample accommodation volume100, needle112, seat114, and sample drive102embodied as metering device are connected to an optional flush pump180.

In the switching state according toFIG.2, a fluidic connection is established from the fluid drive20via fluidic ports1,6and conduits110,155of the fluidic valve95up to separation unit30. A further fluidic connection is established from flush pump180via fluidic ports2,3and conduits110,155of fluidic valve95, sample drive102, sample accommodation volume100, needle112, seat114, back to fluidic valve95and from there to waste166.

Now referring to the switching state ofFIG.3, the sample drive102is operable and the fluidic valve95is switched into a draw and decompress/compress switching state in which a predefined overpressure is adjustable in the sample accommodation volume100before switching the fluidic valve95for injecting the fluidic sample towards the separation unit30.

In the draw and de-/compress position of the fluidic valve95according toFIG.3, the fluid drive20or analytical pump is connected to separation unit30or liquid chromatography column. Sample accommodation volume100(also denoted as loop), needle112, seat114, and sample drive102or metering device are blocked. Hence, decompressing or compressing fluid within the injector40is possible in the switching state according toFIG.3. Furthermore, it is possible to draw fluidic sample in the switching state according toFIG.3.

In the switching state according toFIG.3, a fluidic connection is established from the fluid drive20via fluidic ports1,6and conduits110,155of the fluidic valve95up to separation unit30. The flush pump180is disconnected. A further fluidic connection is established from sample drive102, via sample accommodation volume100, needle112, seat114, back to blocked fluidic port5of fluidic valve95.

Referring toFIG.4, the fluidic valve95has been switched to a feed inject position. Now, fluid drive20is fluidically connected to the same flow path104to which also sample drive102is fluidically connected. Sample accommodation volume100, needle112, seat114, sample drive102are fluidically connected to valve-internal fluidic T-piece or fluidic connection108which is formed by and located at the position of static fluidic port6(compareFIG.4). By defining the fluidic connection108or the bifurcation point of the fluidic T-piece by static fluidic port6and hence as part of the stator of the fluidic valve95, a particular precisely defined and reproducible fluidic connection108may be established with low or no dead volume. With a plunger movement of the sample drive102or metering device, the previously intaken fluidic sample can be injected towards separation unit30.

More particularly, in an injection switching state of the fluidic valve95as shown inFIG.4, the fluid drive20, the separation unit30and the sample drive102are fluidically coupled by the fluidic valve95so that fluid (such as the fluidic sample) driven by the sample drive102and flowing from the sample accommodation volume100to the separation unit30and further fluid (such as a mobile phase, for instance a solvent composition) driven by the fluid drive20and flowing from the fluid drive20to the separation unit30are combined or mixed at fluidic connection108upstream of the separation unit30. The combination of the two fluid streams at fluidic connection108are indicated inFIG.4by arrows177,199. Hence, both fluid streams combine at the fluidic connection108to a common fluid stream flowing towards the separation unit30. In the injection switching state according toFIG.4, the control unit70is configured for controlling a pressure of fluid (in particular fluidic sample) driven by the sample drive102and/or further fluid (in particular a mobile phase configured as a solvent or a solvent composition) driven by the fluid drive20during injecting fluidic sample from the sample accommodation volume100into the flow path104. Consequently, in particular the pressure of the combined fluid comprised of mobile phase and fluidic sample may be controlled. The fluid pressure may be controlled in particular at the fluidic connection108between the fluid drive20, the separation unit30and the sample drive102. As a basis for the operation of the system, the pressure may be measured at one or several locations (for instance at the sample drive102and/or at the fluid drive20and/or at and/or downstream of the fluidic connection108, for instance by one or more pressure sensors, etc.). The measured pressure value(s) may be compared with a respective threshold value. Fluid drive pressure of the fluid drive20and/or of the sample drive102may then be adjusted individually or in common under control of control unit70to bring the actual pressure value(s) in accordance with the respective threshold value. More specifically, the control unit70is configured to keep the pressure at the fluidic connection108constant during injection. The control unit70synchronizes operation of the fluid drive20and the sample drive102for controlling the pressure. In the injection switching state according toFIG.4, the control unit70can also be configured for adjusting a mixing ratio between mobile phase driven by the fluid drive20and fluidic sample driven by the sample drive102towards the separation unit30at the fluidic connection108. In the injection switching state of the fluidic valve95, the fluid drive20, the separation unit30and the sample drive102are fluidically coupled at fluidic coupling point108which is defined by the fluidic valve95. More precisely, the fluidic coupling point108is located in an interior of the active fluidic valve95in this switching position according toFIG.4. As can be taken fromFIG.4, the fluid drive20and the sample drive102are controllable for injecting a predefined fluidic sample-mobile phase mixture by mixing, at the fluidic connection108, the fluidic sample driven102by the sample drive102and a mobile phase driven by the fluid drive20with a predefined mixing ratio. The mixing ratio can be adjusted by adjusting the individual flow rates, in particular by adjusting a volume over time displacement characteristics of the involved pistons.

In the above described switching state according toFIG.3, the sample drive102may be also operated under control of the control unit70for intaking a large multi-portion amount of fluidic sample into the sample accommodation volume100. Subsequently, in the switching state according toFIG.4, it is possible to inject these multiple portions of the previously intaken amount of fluidic sample towards the separation unit30during different discontiguous (or discontinuous) time intervals. The individual portions may then be separated temporally spaced by one or more predefined delay times.

Thus, switching fluidic valve95of the injector40into the injection switching state according toFIG.4, the fluidic valve95fluidically couples the fluid drive20, the sample drive102and the separation unit30at a fluidic T-point defined by the fluidic connection108in an interior of the fluidic valve95. In this injection switching state, the fluidic sample can be injected from the sample accommodation volume100into the part of the flow path104guiding from the fluidic connection108towards the separation unit30. At the same time, another fluid stream of mobile phase is pumped from the fluid drive20via the fluidic connection108towards the separation unit30.

In the switching state according toFIG.4, a fluidic connection is established from the fluid drive20via fluidic ports1,6and conduits110,155of the fluidic valve95up to separation unit30. The flush pump180is disconnected. A further fluidic connection is established from sample drive102, via sample accommodation volume100, needle112, seat114, back to fluidic port5of fluidic valve95and from there to fluidic connection108. At fluidic connection108, the fluid streams originating from fluid drive20and originating from sample drive102are mixed or combined.

As can be taken fromFIG.4, the fluidic coupling point108in the shown injection switching mode is defined by one fluid port6being fluidically coupled to one fluid conduit110at a central position of this fluid conduit110. The fluid port6is further fluidically connected to a capillary111(forming part of the flow path104) guiding towards the separation unit30.

Referring toFIG.5, an inject position is shown.

In the switching position of the fluidic valve95according toFIG.5, the fluidic sample is injected towards the separation unit30driven by the fluid drive20while the sample accommodation volume100is located downstream of the fluid drive20and upstream of the separation unit30. Hence, the fluidic valve95does not form (or no longer forms) a fluidic T-piece between fluid drive20, separation unit30, and sample accommodation volume100in the further injection switching state according toFIG.5. In contrast to this, a continuous fluid connection is established from fluid drive20, via fluid valve95, sample drive102, sample accommodation volume100, needle112, seat114, again fluidic valve95, and separation unit30. In this other injection switching state, fluid driven by the fluid drive20flows through the sample drive102and the sample accommodation volume100before flowing to the separation unit30.

As can be taken from a comparison ofFIG.4andFIG.5differing substantially concerning a switching position of fluidic valve95, the control unit70is configured for controlling switching of the fluidic valve95so as to select one of:a feed injection mode in which the fluidic sample is injected in the injection switching state (compareFIG.4); ora flow-through mode in which the fluidic sample is injected in the other switching state (compareFIG.5).

In the feed injection mode ofFIG.4, a defined and adjustable mixture or dilution of the fluidic sample with mobile phase is enabled. In the flow-through mode ofFIG.5however, the fluidic sample is transported as a fluid packet delimited between mobile phase packets, but being substantially free of mixing or dilution. The valve design according toFIG.2toFIG.5allows to provide an injector40offering both described injection functionalities according toFIG.4orFIG.5.

FIG.6Ashows ports1-6and grooves as fluid conduits155of a stator600of the fluidic valve95according toFIG.2toFIG.5.FIG.6Bshows grooves as fluid conduits110of a rotor650of the fluidic valve95according toFIG.2toFIG.5.

FIG.7illustrates an injector40according to another exemplary embodiment of the invention having a fluidic valve95with a stator having ports1-6but no grooves and with a rotor having grooves as fluid conduits110. The embodiment ofFIG.7differs from the embodiment ofFIG.2toFIG.6Bconcerning shape, position and dimensioning of the groove-type conduits110and concerning the position of the fluid ports1to6. These examples show that the functionality described referring toFIG.2toFIG.6Bcan be achieved with different valve designs. As indicated with reference numeral155inFIG.2toFIG.6B, part of the fluidic conduit110is embodied as stator grooves, whereas the rest of the fluid conduits110(not being indicated with reference numeral155) are embodied as a rotor grooves according toFIG.2toFIG.6B. In contrast to this, the design according toFIG.7does not require stator grooves, i.e. has all fluidic conduits110embodied as rotor grooves.FIG.7furthermore shows that a fluidic restriction171and/or a check valve144can be implemented between the fluidic valve95and waste166. This provision can also be taken according toFIG.2toFIG.6B. As substitute for flush pump180, the embodiment ofFIG.7implements a solvent bottle191.

FIG.8toFIG.13illustrate an injector840according to another exemplary embodiment in different switching states.FIG.8toFIG.13show another example of a dual-functionality (or dual-mode, or hybrid) valve configuration. Namely, the injector840is capable of operating in a feed injection or a flow-through needle (FTN) injection mode of operation, and switching between these two modes. The hybrid configuration of the injector840allows flexibility in method development and method transfer.

An aspect of the embodiment ofFIGS.8-13is that the injector840allows for controlled, active compression of a metered fluidic sample, in particular pre-compression of the fluidic sample prior to injecting the fluidic sample into the high-pressure analytical flow path (i.e., mobile phase stream). Moreover, the (pre)compression may be performed in either the feed injection or flow-through needle injection mode of operation. Sample (pre)compression prior to injection in liquid chromatography, particularly high-performance liquid chromatography (HPLC) including ultra-high performance liquid chromatography (UHPLC), allows to minimize the reduction in pressure in the analytical flow path upon injection, typically referred to as the “pressure drop.” By doing so in a controlled and active manner (for example by making use of a sensory setup involving a single sensor or (differential) sensors, and a metering device to perform the compression), the deleterious effects attending such pressure drop may be significantly reduced or even completely avoided. Such deleterious effects include destabilization of the fluid flow, and destabilization of the solvent composition provided by the analytical pump (especially for high-pressure pumps, which mix the solvents at high pressure), distortion of the flow profiles in the analytical column, and possibly even backflow. Such effects may negatively affect the reproducibility of the analytical measurement, for example leading to instability of retention times, separation resolution, etc. Negative effects for column performance and lifetime can also be associated with this pressure drop, including disruption of the packed-particle bed of the analytical separation column which may result in the formation of voids or preferential flow paths, as well as deterioration of chemical and mechanical properties of the stationary-phase particles. Pre-compression may thus significantly improve column lifetime and reduce costs of operation.

While, according to this embodiment, pre-compression may be implemented for the flow-through needle injection mode as well as the feed injection mode, it is not per se required (i.e., it is optional) for the flow-through needle injection mode. This flexibility may enhance method transfer capabilities. It is also possible to perform partial pre-compression should this be useful for method transfer purposes.

Referring toFIG.8, the injector840includes a fluidic valve895having a configuration based on a stator and rotor as generally described elsewhere herein. The layouts of the stator and rotor are shown separately inFIGS.14A and14B. Specifically,FIG.14Aillustrates the architecture or pattern of ports1-8and stator grooves155of the stator1400, andFIG.14Billustrates the architecture or pattern of rotor grooves110,111of the rotor1450, of the fluidic valve895shown inFIGS.8-13. In the present embodiment, the stator1400includes one port1located at the center of the stator1400, and two other groups of ports2-3and4-8are located at two different radii or circumferences relative to the center, respectively. The stator1200also includes a plurality of arcuate stator grooves155. The rotor1250includes a plurality of arcuate rotor grooves110and one radial rotor groove111. The radial rotor groove111extends from the central port1(when the stator1400and the rotor1450are assembled together) to one end of one of the arcuate rotor grooves110. That is, the radially outermost end of the radial rotor groove111adjoins or is coincident with one end of the corresponding arcuate rotor groove110.

Referring toFIG.8, as in other embodiments disclosed herein, the injector840is configured for injecting a fluidic (e.g., liquid) sample into a (main or analytical) flow path104between the high-pressure fluid drive (or analytical pump)20and the separation unit (e.g., chromatography column)30. Thus, the injector840further includes the sample loop or sample accommodation volume100for accommodating a certain (i.e., predefined) amount of fluidic sample prior to injecting the fluidic sample into the flow path104, the sample drive102(e.g., configured as a metering pump with a linearly translating piston188), a sample needle100movable between an in-line needle seat114and a sample container (e.g., vial, not shown), a waste (line and container)166, and an optional flush pump180(or alternatively a liquid container) for supplying a wash solvent. The respective operations of the foregoing components, including the switching of the fluidic valve895to different switching states and the movement (linear translation) of the piston188(e.g., piston velocity, stroke length, direction of travel, etc.), may be controlled by the control unit70described herein.

FIG.8illustrates a draw and (pre)compress/decompress switching state of the fluidic valve895when in the feed injection mode. In this state, the fluid drive20is connected to the separation unit30via the flow path104. Specifically, the fluid drive20is connected to the separation unit30via ports1and6(and associated fluid lines connected, respectively, between port1and the fluid drive20and between port6and the separation unit30) and the grooves interconnecting ports1and6—namely, the radial rotor groove111, the arcuate rotor groove110adjoining the radial rotor groove111, and the stator groove155overlapping with that arcuate rotor groove110. Separately, the sample drive102is connected to the sample accommodation volume100and needle112via ports7and8(and associated fluid lines connected, respectively, between port7and the sample accommodation volume100, and between port8and the sample drive102) and the rotor groove110interconnecting the ports7and8at this switching state. The waste166and flush pump180are disconnected and inactive in this switching state.

In the switching state ofFIG.8, the sample accommodation volume100is isolated from the high-pressure flow path104and thus may be at a much lower pressure compared to the flow path104, for example at or around atmospheric pressure. Accordingly, the needle100may be disengaged from the seat114and driven to move to a sample container (not shown), and the sample drive102may then be operated to draw a controlled amount of fluidic sample from the sample container into the sample accommodation volume100via the needle100, for example by moving the piston188of the sample drive102rearward (to the right inFIG.8). After the fluidic sample has been loaded into the sample accommodation volume100, the needle112may be driven to move back into a seated position in the seat114. The seat114is connected to port5, which is blocked in the switching state ofFIG.8. Accordingly, as in other embodiments described herein, subsequent to loading the sample accommodation volume100and reseating the needle112, the sample accommodation volume100(and associated fluid lines) may be (pre)pressurized to a desired pressure level, for example by moving the piston188forward (to the left inFIG.8), prior to injecting the fluidic sample into the flow path104. As noted above, the sample accommodation volume100may be pressurized to match the pressure of the high-pressure flow path104, or at least to a level that avoids a significant, deleterious pressure differential when switching into the feed injection switching state described below in conjunction withFIG.9(in particular, to avoid an abrupt pressure drop in the analytical flow path104upon injection). Additionally, subsequent to sample injection, the sample accommodation volume100(and associated fluid lines) may be depressurized prior to reloading (drawing additional sample into) the sample accommodation volume100, for example by moving the piston188of the sample drive102rearward in a controlled manner, thereby avoiding a significant pressure differential when switching out of the feed injection switching state.

FIG.9illustrates a feed injection switching state of the fluidic valve895when in the feed injection mode. In this state, the rotor has been rotated clockwise relative to the stator such that a bifurcated (or a T-piece or Y-piece) fluidic connection (or fluidic coupling point)108is established and located at port5to which the sample accommodation volume100is connected via the needle112, seat114, and associated fluid lines. In this state, the fluid drive20remains connected to the separation unit30via the flow path104. As in the draw and (pre/de)compress switching state ofFIG.8, the fluid drive20is connected to the separation unit30via ports1and6(and associated fluid lines connected to ports1and6) and the same grooves interconnecting ports1and6(the radial rotor groove111, the arcuate rotor groove110adjoining the radial rotor groove111, and the stator groove155overlapping with that arcuate rotor groove110). However, now the flow path104additionally includes port5between ports1and6where the fluidic connection108with the sample accommodation volume100is formed. Also in the feed injection switching state, the sample drive102remains connected to the sample accommodation volume100and needle112via ports7and8(and associated fluid lines connected to ports7and8) and the rotor groove110interconnecting the ports7and8. However, now the sample drive102is additionally connected to the flow path104via the fluidic connection108defined at port5. Accordingly, the stream of mobile phase originating from the fluid drive20(depicted by arrow177) and the stream of fluidic sample originating from the sample accommodation volume100(depicted by arrow199) are mixed (or combined, or merged) at the fluidic connection108. By this configuration, the sample drive102may be operated to inject the fluidic sample from the sample accommodation volume100into the flow path104via the fluidic connection108, for example by moving the piston188forward to drive the fluidic sample in the direction of port5, whereby the fluid sample is thereafter transported with the mobile phase in the flow path104to the separation unit30for analytical or preparative separation. The waste166and flush pump180remain disconnected and inactive in the feed injection switching state.

The feed injection mode described above is advantageous because it enables the sample drive102to be utilized to actively pre-compress the metered amount of fluidic sample contained in the sample accommodation volume100. Moreover, the feed injection mode injects the pre-compressed fluidic sample by merging it into the analytical flow path104at a controlled velocity, thereby providing a modality for controlling the mixing ratio of the fluidic sample with (or dilution of the fluidic sample by) the mobile phase, and more generally providing a greater degree of control over the conditions of the sample introduction. In particular, feed injection enables altering the composition of the fluidic sample, and thus mediate incompatibilities between the fluidic sample, the sample solvent, the mobile phase, and the stationary phase. Feed injection may be with characterized by an extremely low delay volume, low sample dispersion, and zero (or near-zero) dead volume.

FIG.10illustrates a draw and (pre)compress/decompress switching state of the fluidic valve895when in the flow-through needle (FTN) injection mode. In this state, the rotor is located at an angular position counterclockwise to that illustrated inFIG.8. The fluid drive20is connected to the separation unit30via the flow path104. Specifically, the fluid drive20is connected to the separation unit30via ports1and6(and associated fluid lines connected to ports1and6) and the grooves interconnecting ports1and6—namely, the radial rotor groove111, the arcuate rotor groove110adjoining the radial rotor groove111, and the stator groove155overlapping with that arcuate rotor groove110. Separately, the sample drive102is connected to the sample accommodation volume100and needle112via ports7and8(and associated fluid lines connected to ports7and8) and the rotor groove110and overlapping stator groove155that interconnect the ports7and8at this switching state. The waste166and flush pump180are disconnected and inactive. Sample loading, (pre)pressurizing, and depressurizing operations may be carried out as described above.

FIG.11illustrates a flow-through injection switching state of the fluidic valve895when in the flow-through needle (FTN) injection mode. In this state, the rotor is located at an angular position counterclockwise to that illustrated inFIG.10. In this state, the sample accommodation volume100has been coupled into, and is now part of, the flow path104between the fluid drive20and the separation unit30. Hence, as in the embodiment ofFIG.5, the sample accommodation volume100is now located downstream of the fluid drive20and upstream of the separation unit30, and the fluidic connection108established in the feed injection mode at port5is not defined or utilized in the flow-through injection mode. Specifically in the present embodiment, the fluid drive20is connected to the sample accommodation volume100via ports1and7(and associated fluid lines) and the grooves interconnecting ports1and7(the radial rotor groove111, the arcuate rotor groove110adjoining the radial rotor groove111, and the stator groove155now overlapping with that arcuate rotor groove110). In turn, the sample accommodation volume100, needle112, and seat114, which are in-line between ports7and5, are connected to the separation unit30via ports5and6and the overlapping rotor groove110and stator groove155interconnecting ports5and6. Accordingly, in this embodiment, the fluid drive20drives the fluidic sample from the sample accommodation volume100, through the needle112and seat114, and to the separation unit30together with the mobile phase.

In comparison to flow-through injection, a characteristic of flow-through needle (FTN) injection is that the sample drive102as well as the waste166and flush pump180are disconnected and inactive during the flow-through injection switching state. That is, the sample drive102is not switched in-line with the analytical flow path104. As such, the sample drive102is not required to be able to withstand the high pressures associated with the analytical flow path104. Additionally, the bypassing of the sample drive102may significantly reduce delay volume compared to a flow-through injection configuration (which switches the metering device into the analytical flow path).

Moreover, previously known FTN configurations lack the ability to perform pre-compression of the fluidic sample. However, as can be taken from the foregoing description, the FTN configuration of the presently disclosed embodiment enables active, controlled pre-compression prior to injection while also allowing for bypassing the metering device (e.g., sample drive102) during injection. A reduction of delay volume may lead to improved chromatographic performance in gradient liquid chromatography, as the imposed gradient arrives at the column head faster and less gradient dispersion has taken place. This also allows to use a high-pressure metering device (e.g., sample drive102) featuring a volume in the range of, for example 100 microliters (mL) to 500 mL. Such a relatively high-volume sample drive102allows it to also be utilized, if desired, to effectively flush the entire fluidic path, which omits the use of an additional pumping unit (e.g., flush pump180). However, embodiments making use of an additional pumping unit will exhibit the same functionalities, and are encompassed within the present disclosure.

FIG.12illustrates a wash/bypass switching state of the fluidic valve895, which may be implemented in conjunction with either the feed injection (FIGS.8-9) or flow-through injection (FIGS.10-11) mode of operation. In this state, the rotor is rotated to a position at which the sample accommodation volume100, sample drive102, and associated fluid lines are placed in-line with the flush pump180and waste166. The fluid drive20is connected to the separation unit30via ports1and6, which are interconnected by the radial rotor groove111and the adjoining arcuate rotor groove110. Separately, a wash fluid flow path (for a suitable wash solvent) is established between the flush pump180and waste166. Specifically, the flush pump180is connected to the sample drive102via ports2and3and the rotor groove110and overlapping stator groove155interconnecting ports2and3. The sample drive102, which is in-line between ports3and8, in turn is connected to the sample accommodation volume100(and needle112and seat114) via ports8and7(and associated fluid lines connected to ports8and7) and the rotor groove110and overlapping stator groove155interconnecting ports8and7. The sample accommodation volume100(and needle112and seat114) in turn is connected to waste166via ports5and4(and associated fluid lines connected to ports5and4) via the rotor groove110interconnecting ports5and4. The wash/bypass switching state is useful for washing or flushing the sample accommodation volume100and associated fluid lines between different sample injection events to prevent cross-contamination. The wash/bypass mode may be facilitated by the use of passive check valves805placed in appropriate locations in the wash fluid flow path, such as in the flush pump output line and the waste line.

FIG.13illustrates a purge switching state of the fluidic valve895, which may be implemented in conjunction with either the feed or flow-through injection mode of operation. In this state, rotor is rotated to a position at which the fluid drive20is connected to waste166(via port1, radial rotor groove111, adjoining arcuate rotor groove110, and port4) instead of to the separation unit30.

As in other embodiments, fluid pressure may be controlled at one or more locations of the injector840, and for this purpose, one or more pressure sensors and/or flow sensors may be appropriately positioned and interface with the control unit70. In the case of feed injection (FIGS.8and9), the fluidic sample/mobile phase mixing ratio (e.g., at the fluidic connection108) may be controlled and adjusted, as in other embodiments. Moreover, multiple portions of previously intaken amounts of fluidic sample may be injected during different time intervals.

In any of the embodiments disclosed herein, the fluidic valve (e.g.,95or895) may be configured such that the needle seat is integrated with the stator of the fluidic valve. For example, the needle seat may be integrated or co-located with the port (e.g., port5) with which the needle seat (e.g., seat114) is shown to be connected in the various drawing figures of this disclosure. Such integration of the needle seat with the sample injection valve may minimize delay volume, dead volume, sample dispersion, and sample carry-over.

It should be noted that the term “comprising” does not exclude other elements or features and the term “a” or “an” does not exclude a plurality. Also elements described in association with different embodiments may be combined. It should also be noted that reference signs in the claims shall not be construed as limiting the scope of the claims.