CONFIGURING AN INJECTOR FOR EMULATING OPERATION OF ANOTHER INJECTOR
20220128519 · 2022-04-28
Inventors
Cpc classification
F16K11/074
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
International classification
F16K11/074
MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
Abstract
A configurable injector for injecting a fluidic sample in a separation path of a sample separation apparatus includes a sample accommodation volume for accommodating the fluidic sample to be injected into the separation path, a valve arrangement fluidically couplable with the separation path, fluidically coupled with the sample accommodation volume, and being controllable for injecting the fluidic sample into the separation path, an input interface configured for receiving input data indicative of an injection profile of an injector to be emulated by the configurable injector, and a control unit configured for controlling the configurable injector, in particular the valve arrangement, so that the configurable injector is operated in accordance with the injection profile to thereby emulate the injector to be emulated.
Claims
1. A method of injecting a fluidic sample in a separation path of a sample separation apparatus by correspondingly configuring a configurable injector to emulate operation of an injector to be emulated, wherein the configurable injector comprises a sample accommodation volume for accommodating the fluidic sample to be injected into the separation path, and a valve arrangement fluidically coupled with the sample accommodation volume, and being configured for injecting the fluidic sample into the separation path, the method comprising: receiving, by the configurable injector, input data indicative of an injection profile of the injector to be emulated; and configuring the configurable injector by configuring the valve arrangement, so that the configured injector is operated in accordance with the injection profile and thereby emulates the injector to be emulated.
2. The method according to claim 1, comprising at least one of the following features: controlling a metering device for driving the fluidic sample into and/or out of the sample accommodation volume so that the configured injector is operated in accordance with the injection profile and thereby emulates the injector to be emulated; controlling the configured injector in accordance with the injection profile to selectively emulate the injector to be emulated operating in accordance with feed injection or in accordance with sample loop injection, depending on the received input data; comparing characteristics of the configurable injector with characteristics of the injector to be emulated in accordance with the injection profile, and adjusting operation of the configurable injector so that the adjusted operation of the configurable injector is compliant with the injection profile; emulating the injector to be emulated by configuring the configurable injector so that a separation result obtained when operating the sample separation apparatus with the configured injector, is identical to a separation result obtained when operating the sample separation apparatus with the injector to be emulated; emulating the injector to be emulated by configuring the configurable injector so that the configurable injector emulates a switching of the sample accommodation volume accommodating fluidic sample into the separation path in accordance with the injection profile; emulating the injector to be emulated by configuring the configurable injector so that a flow rate dip, occurring when operating the injector to be emulated, is emulated by the configurable injector; emulating the injector to be emulated by configuring the configurable injector to emulate injection of the fluidic sample in the separation path without a pre-compression of the fluidic sample in the sample accommodation volume prior to injecting the fluidic sample into the separation path; emulating the injector to be emulated by configuring the configurable injector to emulate injection of the fluidic sample in the separation path with a pre-compression of the fluidic sample in the sample accommodation volume prior to injecting the fluidic sample into the separation path; emulating the injector to be emulated by configuring the configurable injector to operate so that a gradient profile of mobile phase is emulated in accordance with the injection profile; emulating the injector to be emulated by configuring the configurable injector to dilute fluidic sample with a diluent in accordance with the injection profile; emulating the injector to be emulated by configuring the configurable injector so that an interior volume of the injector to be emulated is added as additional fluid flow prior to starting a separation run, in particular a gradient run, by the configured injector; emulating the injector to be emulated by configuring the configurable injector to inject the fluidic sample into the separation path with a velocity characteristic in accordance with the injection profile; emulating the injector to be emulated by configuring the configurable injector to adjust a volume of the injected fluidic sample for compensating a leakage characteristic of the injector to be emulated; emulating the injector to be emulated by configuring the configurable injector to operate in accordance with a flow rate characteristic of the injector to be emulated; emulating the injector to be emulated by configuring the configurable injector to provide a mobile phase composition in accordance with the injection profile; emulating the injector to be emulated by configuring the configurable injector to delay start of a gradient run in accordance with a gradient delay characteristic of the injector to be emulated.
3. A configurable injector for injecting a fluidic sample in a separation path of a sample separation apparatus, the configurable injector comprising: a sample accommodation volume for accommodating the fluidic sample to be injected into the separation path; a valve arrangement fluidically couplable with the separation path, fluidically coupled with the sample accommodation volume, and being controllable for injecting the fluidic sample into the separation path; an input interface configured for receiving input data indicative of an injection profile of an injector to be emulated by the configurable injector; a control unit configured to control the valve arrangement so that the configurable injector is operated in accordance with the injection profile to thereby emulate the injector to be emulated.
4. The configurable injector according to claim 3, comprising a metering device being controlled by the control unit for driving the fluidic sample into and/or out of the sample accommodation volume so that the configurable injector is operated in accordance with the injection profile to thereby emulate the injector to be emulated.
5. The configurable injector according to claim 3, wherein the control unit is configured for controlling the configurable injector in accordance with the injection profile to selectively emulate the injector to be emulated operating in accordance with feed injection or in accordance with sample loop injection, depending on the input data received via the input interface.
6. The configurable injector according to claim 4, wherein the valve arrangement and the metering device are configured for injecting the fluidic sample into the separation path by combining, at a fluidic connection point, the fluidic sample flowing along a sample flow path from the sample accommodation volume with a mobile phase flowing in the separation path, being separate from the sample flow path, of the sample separation apparatus.
7. The configurable injector according to claim 6, wherein the control unit is configured for controlling the valve arrangement and the metering device to emulate another injector to be emulated injecting fluidic sample by switching a sample filled sample accommodation volume into the separation path.
8. The configurable injector according to claim 3, wherein the control unit is configured for: comparing characteristics of the configurable injector with characteristics of the injector to be emulated in accordance with the injection profile; and adjusting operation of the configurable injector so that the adjusted operation of the configurable injector is compliant with the injection profile.
9. The configurable injector according to claim 3, wherein the control unit is configured for emulating the injector to be emulated by configuring the configurable injector so that a separation result obtained when operating the sample separation apparatus with the configured injector is identical to a separation result obtained when operating the sample separation apparatus with the injector to be emulated.
10. The configurable injector according to claim 3, wherein the control unit is configured for emulating the injector to be emulated by configuring the configurable injector so that the configurable injector emulates a switching of the sample accommodation volume, accommodating fluidic sample, into the separation path in accordance with the injection profile.
11. The configurable injector according to claim 10, comprising one of the following features: wherein the control unit is configured for emulating the injector to be emulated by configuring the configurable injector to emulate injection using a sample accommodation volume without a needle-seat arrangement; wherein the control unit is configured for emulating the injector to be emulated by configuring the configurable injector to emulate injection using a sample accommodation volume in combination with a needle-seat arrangement without a metering device; wherein the control unit is configured for emulating the injector to be emulated by configuring the configurable injector to emulate injection using a sample accommodation volume in combination with a needle-seat arrangement and a metering device; wherein the control unit is configured for emulating the injector to be emulated by configuring the configurable injector to emulate injection of fluidic sample only filling part of the sample accommodation volume.
12. The configurable injector according to claim 3, wherein the control unit is configured for emulating the injector to be emulated by configuring the configurable injector so that a flow rate dip, occurring when operating the injector to be emulated, is emulated by the configurable injector.
13. The configurable injector according to claim 3, wherein the control unit is configured for emulating the injector to be emulated by configuring the configurable injector to emulate injection of the fluidic sample in the separation path without a pre-compression of the fluidic sample in the sample accommodation volume prior to injecting the fluidic sample into the separation path.
14. The configurable injector according to claim 3, wherein the control unit is configured for emulating the injector to be emulated by configuring the configurable injector to emulate injection of the fluidic sample in the separation path with a pre-compression of the fluidic sample in the sample accommodation volume prior to injecting the fluidic sample into the separation path.
15. The configurable injector according to claim 3, wherein the control unit is configured for emulating the injector to be emulated by configuring the configurable injector to operate so that a gradient profile of mobile phase is emulated in accordance with the injection profile.
16. The configurable injector according to claim 3, comprising at least one of the following features: wherein the control unit is configured for emulating the injector to be emulated by configuring the configurable injector to dilute fluidic sample with a diluent in accordance with the injection profile; wherein the control unit is configured for emulating the injector to be emulated by configuring the configurable injector so that an interior volume of the injector to be emulated is added as additional fluid flow prior to starting a separation run by the configurable injector; wherein the control unit is configured for emulating the injector to be emulated by configuring the configurable injector to inject the fluidic sample into the separation path with a velocity characteristic in accordance with the injection profile; wherein the control unit is configured for emulating the injector to be emulated by configuring the configurable injector to adjust a volume of the injected fluidic sample for compensating a leakage characteristic of the injector to be emulated; wherein the control unit is configured for emulating the injector to be emulated by configuring the configurable injector to operate in accordance with a flow rate characteristic of the injector to be emulated; wherein the control unit is configured for emulating the injector to be emulated by configuring the configurable injector to provide a mobile phase composition in accordance with the injection profile; wherein the control unit is configured for emulating the injector to be emulated by configuring the configurable injector to delay start of a gradient run in accordance with a gradient delay characteristic of the injector to be emulated.
17. A sample separation apparatus for separating a fluidic sample, the sample separation apparatus comprising: a fluid drive unit configured for driving a mobile phase and the fluidic sample, when injected in the mobile phase, along a separation path; a configurable injector according to claim 3, configured for injecting the fluidic sample into the separation path in accordance with a received injection profile to thereby emulate an injector to be emulated; and a separation unit configured for separating the fluidic sample injected in the mobile phase in the separation path.
18. The sample separation apparatus according to claim 17, further comprising at least one of the following features: the sample separation apparatus is configured as a chromatography sample separation apparatus; the sample separation apparatus comprises a detector configured to detect separated fractions of the fluidic sample; the sample separation apparatus comprises a fractioner unit configured to collect separated fractions of the fluidic sample; the sample separation apparatus comprises a degassing apparatus for degassing the mobile phase.
19. A computer-readable medium, in which a computer program for injecting a fluidic sample in a separation path of a sample separation apparatus by configuring a configurable injector to emulate operation of an injector to be emulated is stored, wherein the computer program, when being executed by a processor, is configured to carry out or control the method according to claim 1.
20. A program element for injecting a fluidic sample in a separation path of a sample separation apparatus by configuring a configurable injector to emulate operation of an injector to be emulated, wherein the program element, when being executed by a processor, is configured to carry out or control the method according to claim 1.
Description
BRIEF DESCRIPTION OF DRAWINGS
[0055] Other objects and many of the attendant advantages of embodiments of the present invention will be readily appreciated and become better understood by reference to the following more detailed description of embodiments in connection with the accompanied drawings. Features that are substantially or functionally equal or similar will be referred to by the same reference signs.
[0056]
[0057]
[0058]
[0059] The illustration in the drawing is schematically.
[0060] 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.
[0061] A separation result (a chromatogram in case of chromatography) is defined by a combination of the characteristics of the fluidic sample to be separated, a separation method (in particular a chromatographic method) executed, and device characteristics of the sample separation apparatus (in particular a chromatography apparatus). Part of the sample separation apparatus is an injector which has the function to aspirate a fluidic sample from a sample container and to subsequently inject the aspirated fluidic sample into the separation path of the sample separation apparatus. Each injector has its own influence on the separation result.
[0062] According to an exemplary embodiment of the invention, an injector of a sample separation apparatus is configured via an input interface by providing a data set defining the injection profile of another injector which can therefore be emulated or mimicked. Consequently, the configurable injector is subsequently configured in accordance with the input injection profile so that the configured configurable injector behaves as another injector to be emulated would behave if it was implemented in the sample separation apparatus. Therefore, a separation result (such as a chromatogram) may be obtained as if the sample separation apparatus contained the emulated injector. This may enable better comparison of separation results of different sample separation apparatuses, or more precisely of different injectors. In particular, the emulation of the configurable injector may be carried out so that it is not possible to conclude or deduce the type of injection as a result of the emulation. When providing a sample separation apparatus with the described emulation function, it may be sufficient to use and maintain only a single sample separation apparatus (such as a single HPLC) or a single injector and to adapt this single sample separation apparatus or single injector to other chromatographic methods, injection hardware, injection software, etc., without the loss of the opportunity to obtain directly comparable separation results.
[0063] According to an exemplary embodiment of the invention, a configurable injector or sampler is provided which is configured for emulating any other injector or sampler. This may be accomplished in particular by providing a feed injection type injector which is adapted in accordance with an injection profile of an injector or a sampler to be emulated. More specifically, exemplary embodiments of the invention are related to a software, a sampler and a pump combination which is able to emulate any other sampler or injector.
[0064] For instance, a sampler or injector without any dead volume adding to the main path is able to behave as any other sampler by shifting the start of the gradient to a time representing this sampler volume divided by an actual flow rate.
[0065] An advantage of a configurable injector according to an exemplary embodiment of the invention is that it may involve substantially no dead volume. Advantageously, a metering device, a loop, a needle and a seat may be purgeable by a flushing device (for instance an installed flush pump with one or more, in particular three, solvents). Preferably, a pre-compression feature may be provided by the configurable injector, in particular for a feed injection architecture.
[0066] An embodiment may provide a hydraulic junction with the capability to compress and/or decompress a loop, a needle, and/or a seat with the metering device before and/or after switching into or out of the flow path. Furthermore, the metering device may be self-purgeable with fresh solvent which can be provided by a solvent selection valve or a solvent container. In addition, quenching solvent can be dispensed via a metering device to control the reactor fluid.
[0067] Advantageously, exemplary embodiments of the invention may be installable in existing samplers or injectors. A metering device of the injector may be purgeable. Advantageously, an injector or a sampler can be provided which can mime every other sampler by adapting its injection behavior correspondingly, in particular by changing dead volume and injection behavior. This can be done, for instance, by adding dead volume as a loop and/or by shifting gradient. In such an embodiment, a user will only need one injector or sampler to be method compatible with all of its already existing methods. This may also result in saved bench space, because one stack of modules of a sample separation apparatus may be sufficient, instead of many to have certain diversity.
[0068] In order to exclude the needle, seat, loop and metering device from the main path of the reactor fluid path this setup can be used. The sample may be taken by plunger movement of the metering device. The sample draw speed may be adjustable and can be set as method parameter. Highly advantageously, exemplary embodiments of the invention may be operated with only marginal pressure fluctuations (depending on injection mode), in particular when a sample path pre-compression is implemented. Furthermore, a low carryover can be obtained when a purge mode is implemented in which also the needle can be lifted to clean a needle-seat interface (in particular with solvent pumped from flush pump device). In another exemplary embodiment of the invention, a draw volume may be selectable—in particular not limited, selectable in a range of maximum volume of the loop installed. Exemplary embodiments of the invention may also keep the pressure stable, for instance up to 1300 bar or more.
[0069] Referring now in greater detail to the drawings,
[0070] 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 drive unit 20, so that the fluid drive unit 20 already receives and pumps the mixed solvents as the mobile phase. Alternatively, the fluid drive unit 20 might 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 unit 30) occurs at high pressure and downstream of the fluid drive unit 20 (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.
[0071] A data processing unit or control unit 70, 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 device 10 in order to receive information and/or control operation. For example, the control unit 70 may control operation of the fluid drive unit 20 (for example setting control parameters) and receive therefrom information regarding the actual working conditions (such as output pressure, etc. at an outlet of the pump). The control unit 70 may also control operation of the solvent supply 25 (for example setting the solvent/s or solvent mixture to be supplied) and/or the degasser 27 (for example 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 unit 70 might further control operation of the sampling unit or injector 40 (for example controlling sample injection or synchronization sample injection with operating conditions of the fluid drive unit 20). The separation unit 30 might also be controlled by the control unit 70 (for example selecting a specific flow path or column, setting operation temperature, etc.), and send—in return—information (for example operating conditions) to the control unit 70. Accordingly, the detector 50 might be controlled by the control unit 70 (for example with respect to spectral or wavelength settings, setting time constants, start/stop data acquisition), and send information (for example about the detected sample compounds) to the control unit 70. The control unit 70 might also control operation of the fractionating unit 60 (for example in conjunction with data received from the detector 50) and provides data back.
[0072]
[0073] Highly advantageously, the injector 40 is embodied as a configurable injector 40 for injecting a fluidic sample in a separation path 102 between fluid drive unit 20 and separation unit 30, i.e. as an injector 40 which can be reconfigured to execute or mimic another injection scheme. As shown in
[0074] Furthermore, an input interface 106 of the injector 40 is foreseen and configured for receiving input data indicative of an injection profile of an injector to be emulated (see for instance the injector 108 of
[0075] As can be taken from
[0076]
[0077] The sample separation apparatus 10 corresponding to the configurable injector 40 of
[0078] A metering device 123 (such as a syringe pump) cooperates with the valve arrangement 104, with the sample accommodation volume 100 (here embodied as sample loop), with a needle 125 and with a seat 127. In the configuration according to
[0079] Thereafter, the needle 125 may be driven back (for instance by a robot) into the seat 127 so as to establish again a fluid-tight connection.
[0080] The fluidic sample in the sample accommodation volume 100 may then be injected into the separation path 102 between the fluid drive unit 20 and the separation unit 30 at fluidic connection point 110. In accordance with a feed injection architecture, no sudden switching of the sample accommodation volume 100 into the separation path 102 is performed in such an embodiment. In contrast to this, the fluid stream of mobile phase from fluid drive unit 20 to separation unit 30 may be combined at the fluidic connection point 110 with the separate flow of the fluidic sample which is driven by a forward movement of the piston of the metering device 123 from sample accommodation volume 100 via needle 125, seat 127 and valve arrangement 104 including sample flow path 199 towards the fluidic connection point 110 and from there into the separation path 102 towards separation unit 30. In other words, a first flow of mobile phase flows towards fluidic connection point 110 via a mobile phase flow path. A second flow of fluidic sample flows separately from sample accommodation volume 100 via sample flow path 199 towards the fluidic connection point 110. At the fluidic connection point 110, the first flow and the second flow are combined so as to flow as a common stream to separation unit 30. Thus, two input flow paths and one output flow path meet at the three-conduit junction in form of the fluidic connection point 110. The valve arrangement 104 and the metering device 123 are thus configured for injecting the fluidic sample into the separation path 102 by combining, at fluidic connection point 110, the fluidic sample flowing along sample flow path 199 from the sample accommodation volume 100 with a mobile phase flowing in the separation path 102, being separate from the sample flow path 199, of the sample separation apparatus 10.
[0081] As shown in
[0082]
[0083] When, via the input interface 106, information (such as a parameter set) defining a desired operation of an injector 108 to be emulated is obtained, this information may be supplied to control unit 70. The control unit 70 may calculate an impact of the requested emulation characteristics on the functionality of the injector 40. As a result, the various components of the injector 40 (in particular the valve arrangement 104, the metering device 123, the needle 125, the seat 127 and the robot operating the needle 125, as well as further constituents such as the fluid drive unit 20) may be adjusted so that the emulation of the injector 108 to be emulated can be accomplished by the correspondingly configured injector 40.
[0084] Various options are possible with the configurable injector 40: For instance, the control unit 70 may be configured for emulating the injector to be emulated 108 by configuring the configurable injector 40 so that a chromatogram obtained when operating the sample separation apparatus 10 with the configured injector 40 is identical to a chromatogram obtained when operating the sample separation apparatus 10 with the injector to be emulated 108. Additionally or alternatively, the control unit 70 may be configured for emulating the injector to be emulated 108 by configuring the configurable injector 40 so that the configurable injector 40 emulates a switching of a sample accommodation volume 100 accommodating fluidic sample into the separation path 102 in accordance with the injection profile. For instance, the shown feed injection type injector 40 may be operated so as to behave as a sample loop injection type injector 108, as defined by the input injection profile. Furthermore, the control unit 70 is configured for emulating the injector to be emulated 108 by configuring the configurable injector 40 to emulate injection using a sample accommodation volume 100 without a needle-seat arrangement, with a sample accommodation volume 100 in combination with a needle-seat arrangement 112, 114 but without a metering device, or with a sample accommodation volume 100 in combination with a needle-seat arrangement 112, 114 and a metering device 116. Apart from this, the control unit 70 may be configured for emulating the injector to be emulated 108 by configuring the configurable injector 40 to emulate injection of fluidic sample only filling part of the sample accommodation volume 100, or filling the entire sample accommodation volume 100. It is also possible that the control unit 70 is configured for emulating the injector to be emulated 108 by configuring the configurable injector 40 so that a flow rate dip (which may in particular occur when operating the injector to be emulated 108 in accordance with a sample loop injection architecture) is emulated by the configurable injector 40. The control unit 70 may be further configured for emulating the injector to be emulated 108 by configuring the configurable injector 40 to emulate injection of the fluidic sample in the separation path 102 with or without a pre-compression of the fluidic sample in the sample accommodation volume 100 prior to injecting the fluidic sample into the separation path 102. When the sample separation device 10 is a liquid chromatography device, the control unit 70 is configured for emulating the injector to be emulated 108 by configuring the configurable injector 40 to operate so that a gradient profile of mobile phase is emulated in accordance with the injection profile, for instance taking into account a delay before a gradient run starts. In particular, the control unit 70 can be configured for emulating the injector to be emulated 108 by configuring the configurable injector 40 so that an interior volume of the injector to be emulated 108 is added prior to starting a gradient run by the configurable injector 40. In yet another embodiment, the control unit 70 may be configured for emulating the injector to be emulated 108 by configuring the configurable injector 40 to dilute fluidic sample with a diluent in accordance with the injection profile. Furthermore, the control unit 70 may be configured for emulating the injector to be emulated 108 by configuring the configurable injector 40 to inject the fluidic sample into the separation path 102 with a velocity characteristic defined or indicated by the input injection profile. Beyond this, the control unit 70 may be configured for emulating the injector to be emulated 108 by configuring the configurable injector 40 to adjust a volume of the injected fluidic sample for compensating a leakage characteristic of the injector to be emulated 108. In other words, even if the configurable injector 40 does not suffer from leakage, leakage of the injector to be emulated 108 may be mimicked by supplying a correspondingly reduced amount of fluidic sample or by intentionally draining part of the fluidic sample in accordance with the leakage characteristic of the injector to be emulated 108. Advantageously, the control unit 70 may be configured for emulating the injector to be emulated 108 by configuring the configurable injector 40 to operate in accordance with a flow rate characteristic of the injector to be emulated 108. It is also possible that the control unit 70 is configured for emulating the injector to be emulated 108 by configuring the configurable injector 40 to provide a (in particular modified) mobile phase composition in accordance with the injection profile.
[0085]
[0086] Referring to
[0087] Referring to
[0088] Referring to
[0089] Referring to
[0090] The described functionality of the injector 108 referring to
[0091] It should be noted that the term “comprising” does not exclude other elements or features and the “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.