DE102008000544A1 - Control unit e.g. microprocessor, for fluid sample separation device e.g. high performance liquid chromatography device, is arranged to control rinse cycle, injection cycle and analysis cycle between separation cycles parallel to each other - Google Patents

Abstract

The unit (70) is arranged to control a rinse cycle, an injection cycle and a measurement analysis cycle between sample separation cycles parallel to each other in a temporary manner. The rinse cycle, the injection cycle and the measurement analysis cycle between the sample separation cycles are parameterized independent of each other. Solvent gradients are created at a separation column of a sample separation device (30) with respect to one of the sample separation cycles. The separation column of the sample separation device is rinsed with respect to the rinse cycle. Independent claims are also included for the following: (1) a sample separation device comprising a pump and a sample injector (2) a method for controlling a sample separation device (3) a software program or -product for executing a method for controlling a sample separation device.

Description

TECHNICAL BACKGROUND

The The present invention relates to a control for a sample separation apparatus.

In an HPLC, a liquid (mobile phase) is typically run at a very precisely controlled flow rate (for example, in the range of microliters to milliliters per minute) and at a high pressure (typically 20 bar to 1000 bar and beyond, currently up to 2000 bar ), in which the compressibility of the liquid is perceptible, is moved through a stationary phase (for example a chromatographic column) in order to separate individual components of a sample liquid introduced into the mobile phase from one another. Such an HPLC system is known, for example from the EP 0,309,596 B1 same Applicant, Agilent Technologies, Inc.

One System for liquid chromatography in particular the IC system of the Agilent 1200 series of the assignee Agilent Technologies, Inc., dar.

In Such and other sample separation devices may have a sufficiently precise control of the individual components to be difficult.

EPIPHANY

It It is an object of the invention to provide efficient control of a To enable sample separation device. The task is achieved by means of the independent claims. Further embodiments are in the dependent Claims shown.

According to one exemplary embodiment of the present invention is a control unit for a sample separation device for separating at least one component of a fluidic sample created, wherein the control unit is set up between successive Sample separation cycles one rinse cycle, one injection cycle and control a measurement evaluation cycle in parallel.

According to one Another exemplary embodiment is a sample separation device for separating at least one component of a fluidic sample provided a control unit with the above-described Features.

According to Another exemplary embodiment is a Method for controlling a sample separation device for Separating at least one component of a fluidic sample provided, in the method, the sample separation device is such is controlled between successive sample separation cycles a rinse cycle, an injection cycle and a measurement evaluation cycle be controlled parallel to each other.

According to Another exemplary embodiment is a Software program or product, preferably on a data carrier stored to control or execute the method provided with the features described above, when on a data processing system, for example on a computer.

embodiments The invention can be achieved both by means of a computer program, d. H. software, as well as one or more special ones electrical circuits, d. H. in hardware or in any hybrid Form, d. H. using software components and hardware components, will be realized.

According to one exemplary embodiment of the invention can be Sample Separator be controlled by between two consecutive sample separation cycles while which an actual sample separation takes place, a rinse cycle, one injection cycle and one measurement evaluation cycle parallel in time be performed or controlled to the fastest possible Preparation of the sample separation device for a allow subsequent separation process.

in the Further embodiments of the control unit will be described. These also apply to the sample separation device, the Procedure, the software program and the software product.

The Control unit may be arranged between successive Sample separation cycles the rinse cycle, the injection cycle and perform the measurement evaluation cycle in parallel with each other in time. As a result, three tasks can be massively processed in parallel which reduce the preparation time before disconnecting.

The Control unit can be set up between successive Sample separation cycles the rinse cycle, the injection cycle and independently control the measurement evaluation cycle. A sequence control of these three cycles can thus be separated or functionally decoupled from each other, so that the one cycle has no effect on the other cycle. This also helps speed up the preparation process at.

The control unit may be arranged between successive sample separations cycles to independently parameterize the purge cycle, the injection cycle, and the measurement evaluation cycle. Thus, each of the three cycles can be defined by an independent parameter set, so that the processes of the three cycles can be decoupled from each other and thus error-proofed.

The Control unit may be configured as part of one of the sample separation cycles a solvent gradient to a separation column of the sample separation device. Especially in the As part of a liquid chromatography application, a Sample first on a stationary phase of a Separation column trapped and subsequently by successive change the solvent gradient fractionally from the Column detached. This will find the actual Separation takes place.

The Control unit can be set up as part of the rinse cycle a separation column of the sample separation device do the washing up. After separation, the (for example, chromatographic) separation column should be returned to a state in which a subsequent separation operation without being influenced by the previous one Separation operation can be performed. This can for Example of a rinse solution according to a given scheme can be pumped through the separation column.

The Control unit can also be set up as part of the rinse cycle after rinsing the separation column of the sample separation device to reset a detector of the sample separation device. Such a detector can thus be reset to "zero" so that for a subsequent detection no influence done by a previous detection.

The Control unit may be set up as part of the injection cycle to rinse a sample injector of the sample separation device. Such a sample injector may be a conduit or a flow path in which a needle is retracted into a seat in a conduit is from which she can be driven out by immersion into a sample vessel to inject sample in this path.

The Control unit can be set up as part of the measurement evaluation cycle a calculation based on previously acquired measurements (i.e. a measurement evaluation of a previous sample separation cycle) and / or transferring previously acquired measured values to a coupled unit (for example, storing the measured data in one Memory or forwarding the measured data to a further processing unit) and / or one sample preparation for the next Sample separation cycle (for example, preparation of a measurement unit for a next cycle) or to control.

The Control unit can be set up, the rinsing cycle, the Injection cycle and the measurement evaluation cycle volume-based parameterize. Because of the non-zero volume of a HPLC or more generally of a nonzero system volume a sample separation device can before a subsequent Separation of a sample into different components one parameterized Regeneration of the plant done. Here are the volume properties be taken into account in the system, which benefits the Accuracy of the regeneration procedure increased.

The Control unit can be set up, the rinsing cycle, the Injection cycle and the measurement evaluation cycle in three separate Control channels independently. Thus, the three cycles can be logical and functional be decoupled, causing unwanted interactions between avoids these channels.

in the Further will become embodiments of the sample separation device described. These also apply to the control unit, the Procedure, the computer program and the computer product.

The Sampling device can be a microfluidic measuring device, a life science device, a liquid chromatography device, a HPLC (High Performance Liquid Chromatography), a gas chromatography device, an electrophoresis device and / or a gel electrophoresis device be. However possible for other applications.

The Sample Separator may include a pump for moving a mobile phase. Such a pump can for example be set up, the mobile phase with a high pressure, for example some 100 bar up to 1000 bar and more through the system to pump. Alternatively or additionally, the sample separation device a sample injector for injecting the sample into a mobile phase have the separation column. Such a sample injector can, as described above, a needle in a seat of a corresponding one Have liquid paths that extend out of this seat can to take sample, and after reintroduction injected into the seat the sample into the system. Alternative or supplementary For example, the sample separation device may be a sample fractionator for fractionating the separated components. Such a Fractionator can use the different components for example lead different liquid container. The analyzed sample can also be fed to a waste container become.

Especially can embodiments of the invention in one HPLC can be used, in between two phases of a gradient several regeneration processes can be run through. For example, start conditions can be set then apply a gradient and then the System back to the starting conditions.

Would the system volume of such a sample separation device now hypothetical zero, could after a gradient application phase in principle, start the system immediately. Especially in the real world Case of a non-zero system volume (volume of capillaries, Columns, etc.), it is advantageous to have one between two sample separation cycles To go through the regeneration sequence. This can be, for example, the equilibration a column (rinsing, etc.), bringing one Injector in a start condition condition (rinse) or contain other procedures. A rinse of pillar and injector may take for example 30 seconds. Furthermore it can required or desirable, software and / or or reset a firmware, thus making a calculation to reset a detector (i.e. H. define a current detector signal as zero), a sample with the out of the seat driving a needle and then driving back into the needle (injection), etc.

If Now little time is available, it can be beneficial be to coordinate these phases together or at the same time to expire a user's wait time between two sample separation cycles to keep low.

According to one Embodiment of the invention can now, for example a calculation on the basis of software or firmware in time parallel to the HPLC processes.

It For example, an injector flush can be performed and to define a volume or time with which or during which the injector is purged (Injector can then be rinsed defined). Thus, you can be provided three parallel paths, and thus a decoupling of column control, injector control and measurement evaluation be made. All relevant features of this system are completely parameterized in such an embodiment. As a result, an injection can be reliably controlled.

A Column and injection control can be via volume factors / volume properties be parameterized throughout the system.

BRIEF DESCRIPTION OF THE FIGURES

Other Objectives and many of the attendant advantages of embodiments The present invention will be readily apparent and be better understood with reference to the following more detailed description of embodiments in Related to the attached drawings. Characteristics, which are essentially or functionally the same or similar are provided with the same reference numerals.

1 shows an HPLC system according to an exemplary embodiment of the invention.

2 Figure 4 shows a sequence of a controller for HPLC according to an exemplary embodiment of the invention.

3 to 5 show conventional sequences for controlling HPLC.

The Representation in the drawing is schematic.

1 shows the basic structure of an HPLC system 10 , as it can be used for example for liquid chromatography. A pump 20 drives a mobile phase through a separation device 30 (such as a chromatographic column) containing a stationary phase. A sample application unit 40 is between the pump 20 and the separation device 30 arranged to introduce a sample liquid in the mobile phase. The stationary phase of the separation device 30 is intended to separate components of the sample fluid. A detector 50 Detects separated components of the sample, and a fractionator 60 may be provided to dispense separated components of the sample liquid, for example, in designated containers or a drain.

While a fluid path between the pump 20 and the separation device 30 typically at high pressure, the sample liquid under normal pressure is first in a separate area from the liquid path, a so-called sample loop (English: Sample Loop), the sample unit 40 entered, which then introduces the sample liquid in the high-pressure liquid path. When connecting the initially under normal pressure sample liquid in the sample loop in the high-pressure liquid path, the content of the sample loop abruptly (typically in the range of milliseconds) on the system pressure of the HPLC system 10 brought.

In the configuration according to 1 is a control unit 70 for controlling the individual components of the HPLC system 10 provided and adapted according to the invention, as will be described in more detail below.

The control unit 70 used in the HPLC system 10 out 1 thus controlling the separation process of a component of a fluidic sample.

According to the invention, the control unit 70 (For example, a microprocessor or a CPU, Central Processing Unit) set up so that, as in the sequence 200. according to 2 shown between (for example, each) two consecutive sample separation cycles 202 . 204 during which a solvent gradient 206 to the separation column 30 is applied, a rinse cycle 210 , one injection cycle 220 and a measurement evaluation cycle 230 be controlled in time parallel to each other.

The horizontal direction is clear in 2 the timeline, so that off 2 shows that rinse cycle 210 , Injection cycle 220 and measurement evaluation cycle 230 take place in parallel in three separate process channels. Thus, rinse cycle 210 , Injection cycle 220 and measurement evaluation cycle 230 controlled independently of each other. This also allows the three cycles 210 . 220 . 230 to parameterize independently of each other, and in this case volume properties of the HPLC 10 to take into account.

The rinse cycle 210 contains a step in which a separation column 30 the HPLC 10 is rinsed (see reference numeral 212 ) and contains after rinsing 212 the separation column 30 a phase 214 in which the detector 50 the HPLC 10 is reset.

As part of the injection cycle 220 becomes the sample injector 40 of the sample separation device 10 rinsed (see reference numeral 222 ). reference numeral 224 illustrates that the control unit 70 is set up as part of the injection cycle 220 after rinsing the sample injector 40 the HPLC 10 (Reference 222 ) a sample in the HPLC 10 to inject.

Further, the control unit 70 set up as part of the measurement evaluation cycle 230 perform a software / firmware calculation, for example, to evaluate readings, transfer readings to peripherals, or prepare the sample for the next sample separation cycle.

Thus, due to the control sequence of the control unit 70 a volume-based preparation of the HPLC 10 allows for a subsequent separation procedure.

As in 2 shown, according to the invention is a parallelization of all phases 210 . 220 . 230 possible.

It will be in the measurement evaluation cycle 230 based on a firmware application performing a parameter recovery and an analysis termination. As part of a software application, all data of the run is transferred to a control software (for example in the context of a ChemStation, Cerity, EZChrom, etc.). As part of a software application, a data analysis is also performed (for example, asynchronously with the data acquisition). Software and firmware can help prepare the next sample and initiate the next analysis.

partial step 214 of the rinse cycle 210 serves to the detector 50 to bring in balance. partial step 222 of the injection cycle 220 flushes the injector pass to establish start conditions. partial step 224 can perform an injection with or without a hypodermic needle, or run any injector program.

At the sequence off 2 is a balance 214 after the column equilibration 212 possible. The injection 224 is performed directly after the high-pressure flow path of the injector has been purged (reference numeral 222 ). The sequence 200. guarantees a high reproducibility. To rinse the injector 40 are parameters definable. An independence of calculation times is achieved. For example, the duration of the equilibration phase (reference symbol 212 ), the duration of a rinse phase 222 before removing the injector volume from the high-pressure flow path (so-called bypass position), etc.

3 shows a conventional sequence for controlling HPLC 10 , Between two sample separation cycles 310 . 320 is according to 3 completely serial first a column equilibration 330 , then a software / firmware calculation 340 , below a compensation step 350 , and then an injection step 360 carried out. This is time consuming.

4 shows another conventional sequence 400 in which between two separation runs 310 . 320 temporally parallel a column equilibration 330 on the one hand and in a separate path on the other hand, a software / firmware calculation 340 followed by the balance run 350 and an injection run 360 is carried out.

4 refers to the case that a column equilibration 330 can be done quickly, whereas another in 5 shown scheme 500 refers to the case that the column equilibration 330 takes a relatively long time. In this case, there is still a post-run sequence in the second path 510 intended.

It It should be noted that the term "exhibit" does not excludes other elements and that the "one" does not excludes a plurality. Also, elements, in connection with different embodiments are described combined. It should also be noted the reference numerals in the claims are not considered the scope of protection to be interpreted as limiting the claims.

QUOTES INCLUDE IN THE DESCRIPTION

This list The documents listed by the applicant have been automated generated and is solely for better information recorded by the reader. The list is not part of the German Patent or utility model application. The DPMA takes over no liability for any errors or omissions.

Cited patent literature

• EP 0309596 B1 [0002]

Claims (17)

Control unit for a sample separation device for Separating at least one component of a fluidic sample, wherein the control unit is arranged between successive ones Sample separation cycles one rinse cycle, one injection cycle and control a measurement evaluation cycle in parallel. Control unit according to claim 1, wherein the control unit is established between successive sample separation cycles the rinse cycle, the injection cycle and the measurement evaluation cycle temporally parallel to each other. Control unit according to claim 1 or 2, wherein the control unit is established between successive sample separation cycles the rinse cycle, the injection cycle and the measurement evaluation cycle to control each other independently. Control unit according to one of claims 1 to 3, wherein the control unit is arranged between successive ones Sample separation cycles the rinse cycle, the injection cycle and the measurement evaluation cycle independently of each other parameterize. Control unit according to one of claims 1 to 4, wherein the control unit is set up as part of a the sample separation cycles a solvent gradient to a separation column of the sample separation device to apply. Control unit according to one of claims 1 to 5, wherein the control unit is set up as part of the rinse cycle a separation column of the sample separation device do the washing up. Control unit according to claim 6, wherein the control unit is set as part of the rinse cycle after rinsing the separation column of the sample separation device a Reset the detector of the sample separation device. Control unit according to one of claims 1 to 7, wherein the control unit is set up as part of the injection cycle to rinse a sample injector of the sample separation device. Control unit according to claim 8, wherein the control unit is set up as part of the injection cycle after rinsing the sample injector of the sample separation device a sample into the sample separation device. Control unit according to one of the claims 1 to 9, wherein the control unit is set up in the context of Measurement evaluation cycle to control at least one action from the group consisting of a calculation based on previously acquired measured values, a transfer of previously acquired measured values to a coupled Entity, and a sample preparation for the next sample separation cycle. Control unit according to one of the claims 1 to 10, wherein the control unit is set up, the rinsing cycle, volume based on the injection cycle and the measurement evaluation cycle to parametrize. Control unit according to one of the claims 1 to 11, wherein the control unit is set up, the rinsing cycle, the injection cycle and the measurement evaluation cycle in three separate Control channels independently. Sampling device for separating at least a component of a fluidic sample, wherein the sample separation device a control unit according to one of claims 1 to 12. Sample separation device according to claim 13, selected from the group consisting of a microfluidic measuring device, a life science device, a liquid chromatography device, an HPLC, a gas chromatography device, an electrophoresis device and a gel electrophoresis device. Sample separation device according to claim 13 or 14, further comprising at least one of the features: a pump to move a mobile phase; a sample injector for injection the sample into a mobile phase, a sample fractionator for Fractionating the separated components; an electrophoresis mechanism for the electrophoretically driven propagation of a mobile phase and a sample in the mobile phase. Method for controlling a sample separation device for separating at least one component of a fluidic sample, the method comprising controlling the sample separation device such that a rinsing cycle between successive sample separation cycles, one injection cycle and one measurement evaluation cycle in parallel to be controlled. A software program or product, preferably stored on a disk, to control or execute the method according to the preceding claim, when it's on a data processing system, for example on a computer, expires.