DE102009026640A1 - Sample collecting device for receiving fluid sample, has sample loop for receiving sample volume, sample collecting needle connected with sample loop, and seating device for mounting sample collecting needle in detachable manner - Google Patents

Abstract

The sample collecting device (200) has a sample loop (202) for receiving a sample volume, a sample collecting needle (206) connected with the sample loop, and a seating device (204) for mounting the sample collecting needle in a detachable manner. The sample collecting needle is withdrawn from the seating device for receiving the fluid sample. Independent claims are included for the following: (1) a measuring device for analyzing a fluid sample; and (2) a method for operating a sample collecting device for receiving a fluid sample.

Description

TECHNICAL BACKGROUND

The The present invention relates to sample collection systems for Measuring device.

For liquid chromatography, it is necessary to inject a fluid sample to be tested into the system. Such systems for injecting a fluid sample are out US 4,939,943 . US 3,916,692 or US 3,376,694 known.

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

One Liquid chromatography system provides the LC system Agilent 1200 Series from Applicant Agilent Technologies, Inc. represents.

In Such and other gauges can be an injector for injecting a fluid sample into a path between a high pressure pump and be provided a separation column. In such an injector loop For example, a needle may be placed in a seat, with a receptacle the fluid sample drives the needle out of the seat, in a sample vessel for sucking the fluid sample dips in and then moves back into the seat. After switching over a valve, the fluid sample thus taken up becomes in the high pressure path between the high pressure pump and separation column brought.

at Performing multiple experiments with different samples it may happen that sample material from a previous experiment still contained in small quantities in the capillaries of the injector is, making it an unwanted carry (Carryover) of sample material in a subsequent experiment come can.

EPIPHANY

It It is an object of the invention to provide a sample loading in a meter to allow, without causing an unwanted carry can come from sample material. The task is done by means of the independent Claims solved. Further embodiments are shown in the dependent claims.

According to one exemplary embodiment of the present invention is a sample receiving device for receiving a fluid sample created, wherein the sample receiving device a sample loop for receiving a sample volume, a sample receiving needle, the connected to the sample loop, a seat device for releasable Picking up the sample receiving needle, the sample receiving needle is moved out of the seat assembly to receive the fluid sample, and a purging device adapted to apply with a rinse solution at least partially out of the seat assembly moved sample taking needle, so that the rinse solution through the seat assembly at least partially leaking.

According to one Another exemplary embodiment is a measuring device provided for examining a fluid sample, wherein the measuring device a sample receiving device with the features described above for receiving the fluid sample for injecting into the meter having.

According to Another exemplary embodiment is a Method for operating a sample receiving device for recording a fluid sample, wherein in the method a sample receiving needle is removably received in a seat device, wherein the sample receiving needle with a sample loop for receiving a Sample volume is connected, the sampling needle from the seat assembly is moved out to receive the fluid sample in the sample loop, and a rinse solution at least partially from the seat assembly moved out sample receiving needle acted upon so that the rinse solution through the seating device at least partially exits.

According to an exemplary embodiment of the invention, unwanted sample transfer (carryover) and thus contamination in a measuring device such as a liquid chromatography apparatus can be efficiently avoided by having a rinse solution in the backward direction through the seating device passed through and out of the seating configuration of a sample receiving needle the seating device is brought. Thereby, the seat and also a capillary section adjacent to the seat device can be flushed efficiently. By purging such a critical volume of the sample receiving device prior to injecting a new fluid sample, in an opposite direction to another sample transport direction, the sample receiving device can be efficient be cleaned before a new fluid sample is introduced. This rinse solution (then possibly with traces of the fluid sample from a previous analysis) may exit the sample loop through an opening of the seat assembly from the injector. According to the invention, therefore, at least the seat device can be flushed, optionally also a part of the or the entire sample loop.

in the Further, additional embodiments of the sample receiving device described. These also apply to the measuring device and the procedure.

Especially the flushing device can be set up for rinsing the sample loop through the rinse solution in such a way Pass the sample loop through the rinse solution after flowing through the at least one part of the sample loop through the seat assembly from the sample loop fountain-like exit. Thus, the rinse solution can be sufficient large impulse given to impurities if necessary or sample residues of a previous experiment vividly from the Capillary take near the seat assembly and thus to exert a dynamic force, with which the sample cleaning can be made more efficient.

The Sampling needle can be used to rinse the sample loop be moved out of the seat assembly. Then the rinsing device for purging the sample loop from the seat assembly pulled out sampling needle the rinse solution so pass through the sample loop that the rinse solution after flowing through the at least one part of the sample loop exits the sample loop through the seat assembly. optional may be before, after or parallel to this flushing of a capillary section near the seat assembly also the sample receiving needle rinsed in a separate rinsing vessel by inserting the sample holder needle into this vessel is immersed in another rinse solution and the rinsing solution is sucked into the sampling needle is to be ejected afterwards and thus a cleaning also a capillary section near the sample receiving needle bring about.

The Sampling device may include a rinse solution receptacle for receiving rinsing solution emerging from the seat assembly exhibit. Such a rinsing solution receiving container can be designed as a rinsing solution receptacle, which surround the seating device laterally trough-shaped can. Such a waste tub can emanate from the fountain Rinse solution fluid for cleaning the seat assembly take up.

The Sampling device may be a rinse pump as part have the rinsing device, for example, as peristaltic Rinse pump be configured. Such a flushing pump can be controlled by a control unit to a predetermined Rinse procedure to complete.

The Sampling device may be one with the sample receiving needle coupled and arranged in the sample loop metering device for dosing the fluid sample. Such a metering device may be provided to sample fluid from a sample reservoir (such as for example a vial or a liquid container) into the sample loop of the sample receiving device. Such a metering device can be a piston pump, in particular a high-pressure piston pump, or may as Syringe pump (suction syringe or Syringe) be configured. If the Capillary is flushed near the seat assembly and optional a capillary section is flushed near the needle device is, by means of sucking in such a predefined sample volume into the sample needle and after reinsertion of the sample needle in the suitably designed seating device, the predetermined amount of sample be recorded in the sample loop and after switching a Valve in a path between a high pump and a separation column be injected.

According to one Embodiment, a pumping unit of the metering device, that is, a fluid sample pumping unit, separately from a pumping unit of the purging device, that is a rinsing solution pumping unit may be provided. By separately providing these two components, each of the Components purposefully perform their task. alternative can for the pumping unit of the metering device and be provided by the purging device a common pumping unit, depending on the respective pumping task accordingly is switched.

According to one Embodiment, a conveyor the metering device through the sample loop inverse to a conveyor of the Rinsing device be through the sample loop. Especially may be the conveying of the fluid sample in a state of seat device and sampling needle are performed in which the Sample receiving needle is accommodated in the seat assembly. Then For example, the sample transport in the forward direction through the seat assembly, whereas the rinse solution in the backward direction through the seat device is pumped through.

The purging device may be configured to rinse the sample loop after conveying the fluid sample into the sample loop and after injecting the fluid sample from the sample loop into the meter. Alternatively or additionally, the rinse aid be arranged to flush the sample loop before conveying the fluid sample into the sample loop and before injecting the fluid sample from the sample loop into the meter. By rinsing before and / or after an experiment with a rinse solution, the risk of carryover can be efficiently avoided.

The Flushing device may have a flushing valve, wherein by adjusting a valve position of the purge valve each one of a plurality of different rinsing solutions is selectable for rinsing. Consequently the rinsing process can selectively by means of one, two or done several rinsing solutions. Also complex Purge sequences can thus be traversed.

The Flush valve can, in particular controllable, the seat device in a first rinse a first rinse solution and in a subsequent second flushing a second Add rinse solution, the first Rinse solution a stronger solvent power (for dissolving sample residues from a capillary) can be considered the second rinse solution. For example, can in the first rinse acetonitrile (ACN), methanol or another strong solvent through the seat assembly be pumped to rinse out coarse dirt or sample residues. In a subsequent step, a soft (or softer) Solvent, for example water with 5% ACN or methanol be used to then provide an appropriate starting condition for the further operation of the sample receiving device (Sample Loop or autosampler).

The Sampling device may be an additional rinsing device which, for rinsing the sample receiving needle a additional rinse solution through the Sampling needle passes that the rinse solution after flowing through at least a portion of the sample receiving needle the sampling needle exits. In addition to the rinse the seating device can thus also rinse the sample receiving needle done so that both interfaces of the seat-needle configuration can be kept free of sample residues.

The Sample holding needle can be pressure-resistant, for operation at a pressure of up to about 100 bar, in particular for operation at a pressure of up to about 500 bar, especially for operation at a pressure of up to about 1000 bar and more.

The Sample receiving device may be an injection valve for adjusting of fluid communication properties of the meter. Such an injection valve may have a plurality of ports between which by operating the injection valve selectively different Coupling states can be set.

The Measuring device may be a separating element, in particular a separating column, for separating different fractions of the injected fluid sample. The separation element may be a liquid chromatography separation column be a stationary in the components of a mobile phase Flow through phase and thereby spatially separated Fractions are separated.

The Sample pick-up needle may be in a sample injection path of the meter be arranged.

The Sample Separator can be an HPLC device (High Performance Liquid Chromatography or High Performance Liquid Chromatography), a life science device or an SFC device (Supercritical Fluid Chromatography). However, other applications are possible.

The Meter may include a pump for delivering the injected Fluid sample together with a mobile phase by at least one Part of the meter have. 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 pump through the system.

alternative or in addition, the sample separation device a sample fractionator for fractionating the separated components exhibit. Such a fractionator can be the various components for example in different liquid containers to lead. The analyzed fluid sample can also be a Waste containers are fed.

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 shows a sample receiving device according to an exemplary embodiment.

3 to 5 show an injection path of an HPLC with a sample receiving device according to an exemplary embodiment in different operating states.

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 (see: Sample loop, see. 3 to 5 ), 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.

A control of the HPLC system 10 can by means of a central control unit 70 respectively.

2 clearly shows a sample receiving device 200 for receiving a fluid sample for injecting into the in 1 shown HPLC 10 according to an exemplary embodiment. The configuration of the sample collection device 200 out 2 corresponds to a part of reference numerals 40 out 1 ,

The schematically illustrated sample receiving device 200 contains a sample loop 202 from the in 2 only partial sections are shown. The sample loop 202 is set up to receive a predeterminable sample volume of the fluid sample. A seat device 204 is in the sample loop 202 arranged to a sampling needle 206 with a corresponding geometric configuration form-fitting, releasable and pressure-tight record. In 2 is the sampling needle 206 from the seating device 204 moved out to receive even sample material or to be subjected to a rinse. This period is, as described below, according to 2 also used to attach to the seat 204 adjacent part of the sample loop 202 to wash.

Furthermore, in 2 schematically a purging device 208 shown which for rinsing the sample loop 202 a rinse solution 210 so by the s.den seat device 204 adjacent part of the sample loop 202 passes that rinse solution 210 after flowing through the part of the sample loop 202 through the seat device 204 "Backwards" (that is, opposite a normal fluid directing direction) from the sample loop 202 leakage and due to the retracted state of the sampling needle 206 fountain-like from the seat assembly 204 spouting. The emerging flushing fluid 210 can then from a rinse solution receptacle 212 be included, which is the seat device 204 surrounds laterally.

In the following, reference is made to 3 to 5 a sample injection system 300 described in different operating systems, the sample injection system 300 some of the components of HPLC 10 out 1 contains. With the system according to 3 to 5 may be a contamination by backflushing a seating device 204 be reduced or eliminated.

Before 3 to 5 will be described in more detail, some basic considerations will be made based on which exemplary embodiments of the invention have been developed.

HPLC in combination with mass-sensitive detectors (for example under Use of mass spectrometry) is a powerful become an analytical tool, the detection of traces of materials with a resolution below ppm (parts per million). Due to increasing demands The accuracy of HPLC systems is also getting worse the problem of sample carryover is increasing.

Experiments by the present inventors have indicated that achieving low carryover levels requires additional measures. According to an embodiment of the invention, different flow channels are flushed within the system, in particular a capillary section 202 adjacent to a seat device 204 ,

As the bottom section of a split loop 202 as a sensitive part of the system 300 with regard to carryover, according to the invention can be an area below a seat 204 a sampling needle 206 be rinsed to improve the purity of the system. To avoid adsorptive carryover, according to the configuration of 3 an additional rinse pump 302 as part of the flushing device 208 used to provide a given flow and pressure. This pump 302 can with a detergent selection valve 304 be coupled to from two (as in 3 , see A, B) or several solvents.

Start position of a corresponding operating method of the system 300 is the so-called mainpass position in 3 ,

Apart from the components already described contains 3 also a metering pump 306 , a loop capillary 338 as part of the sample loop 202 , a two-position / six-port valve 308 , a sample container 310 , a first washing container 312 , a second washing container 314 , a third washing container 316 , as well as waste containers 318 . 320 , A peristaltic pump is designated by reference numerals 322 Mistake.

As in 3 also indicated schematically, the sample receiving needle 206 either in the seat assembly 204 retracted, in a flushing port 324 immerse or in the sample container 310 plunge.

3 thus represents the starting position or Mainpassposition in which the pump 20 their flow of split-loop 202 and the valve 308 then through the separation column 30 pump through.

• 1. Das Ventil 308 wird in die in 4 gezeigte Bypass-Position geschaltet. Die Split-Loop 202 wird mittels Anhebens der Nadel 206 geöffnet, und die Nadel 206 wird in eine Position in der Nähe des Sitzes 204 über dem Wastetrichter 212 gebracht (vgl. 5). 5 zeigt somit den Bypass-Modus in einer Konfiguration, in dem Sitz 204 und Kapillare 202 gespült werden können. Die Dosierpumpe 306 bewegt den Kolben dann in Vorwärtsrichtung zu einer Nullposition, und das Volumen in der Split Loop 202 oberhalb der Nadel 206 wird in den Wastetrichter 212 entleert.
• 2. Zu der gleichen Zeit, zu der die Dosierpumpe 306 ihren Kolben in Vorwärtsrichtung drückt, startet die Spülpumpe 302 das Rückspülen des Sitzes 204 mit einer starken Spüllösung (zum Beispiel einem starken organischen Lösungsmittel wie ACN). Wenn eine ausreichende Menge der Spüllösung gespült worden ist, wird die Spüllösung zu einer schwachen Spüllösung hin (typischerweise die Startkondition für die mobile Phase) geändert. Das aus dem Sitz 204 fontänenartig herausfließende Lösungsmittel wird mittels des Wastes 318 gesammelt. Der adsorptive Carryover ist damit aus der Probenaufnahmeschleife 202 entfernt. Das System 300 ist somit bereit, die nächste Fluid-Probe aufzunehmen und zu analysieren.
• 3. Die Nadel 206 wird in den Nadelspülport 324 eingetaucht und mittels einer anderen Spülpumpe 322 (zum Beispiel einer peristaltischen Pumpe) gespült.
• 4. Die Nadel 206 bewegt sich nun in den Probenbehälter 310 hinein und nimmt eine spezifizierte Menge von Fluid-Probe auf.
• 5. In einer weiteren Prozedur wird die Nadel 206 außerhalb des Sitzes 204 wiederum gespült, wie in Prozedur 3. beschrieben.
• 6. Die Nadel 206 wird in den Sitz 204 hineinbewegt, indem eine vertikale Bewegung vollführt wird.
• 7. Das Ventil 308 wird entgegen des Uhrzeigersinns zurück in den Mainpass-Modus geschaltet, womit die Pumpe 20 dazu gebracht wird, die geladene Fluid-Probe auf die analytische Säule 30 aufzubringen, wo der Trennprozess startet.

To inject a fluid sample, the following procedure can be performed:

• 1. The valve 308 will be in the in 4 shown by-pass position. The split loop 202 is done by lifting the needle 206 opened, and the needle 206 will be in a position near the seat 204 above the bin 212 brought (cf. 5 ). 5 thus shows the bypass mode in a configuration in the seat 204 and capillary 202 can be rinsed. The dosing pump 306 then moves the piston in the forward direction to a zero position, and the volume in the split loop 202 above the needle 206 gets into the bin 212 emptied.
• 2. At the same time as the metering pump 306 pushes its piston in the forward direction, the purge pump starts 302 the backwashing of the seat 204 with a strong rinse solution (for example, a strong organic solvent such as ACN). When a sufficient amount of the rinse solution has been rinsed, the rinse solution is changed to a weak rinse solution (typically the mobile phase start-up condition). That from the seat 204 Fountain-like solvent is removed by means of the waste 318 collected. The adsorptive carryover is thus out of the sample collection loop 202 away. The system 300 is thus ready to receive and analyze the next fluid sample.
• 3. The needle 206 is in the Nadelspülport 324 immersed and by means of another flushing pump 322 (for example a peristaltic pump).
• 4. The needle 206 now moves into the sample container 310 and pick up a specified amount of fluid sample.
• 5. In another procedure becomes the needle 206 outside the seat 204 rinsed again, as described in Procedure 3.
• 6. The needle 206 will be in the seat 204 moved in by performing a vertical movement.
• 7. The valve 308 is switched counterclockwise back to the main-pass mode, bringing the pump 20 is brought to the charged fluid sample on the analytical column 30 apply where the separation process starts.

Thus show 3 to 5 schematically two different positions of the injection valve 308 the autosampler 300 within an HPLC system during one injection cycle.

The Mainpass position according to 3 shows the starting or injection position, with the pump 20 with the split loop 202 and the separation column 30 connected is.

In the bypass position according to 4 connects valve 308 the pump 20 directly with the separation column 30 and the split loop 202 with the rinsing pump 302 ,

In the in 5 shown bypass position with seat / capillary backwash connects valve 308 the pump 20 directly with the separation column 30 and the split loop 202 with the rinsing pump 302 ,

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

• - US 4939943 [0002]
• - US 3916692 [0002]
• US 3376694 [0002]
• - EP 0309596 B1 [0003]

Claims (21)

Sample receiving device for receiving a fluid sample, wherein the sample receiving device comprises a sample loop for receiving a sample volume; a sampling needle, which is connected to the sample loop; a seat device for releasably receiving the sample receiving needle; in which the sample receiving needle can be moved out of the seat device, to pick up the fluid sample; and a rinsing device, adapted for applying a rinse solution in an at least partially moved out of the seat assembly Sampling needle, so that the rinse solution through the seating device at least partially exits. The sample receiving device according to claim 1, wherein the Flushing device is set up, the rinse solution at least partially moved out of the seat assembly Sampling needle to act such that the rinse solution through the seating device fountains. Sample receiving device according to claim 1 or 2, comprising a rinse solution receptacle for receiving rinsing solution emerging from the seat assembly. A sample receiving device according to claim 3, wherein said Rinse solution receptacle as flushing solution receptacle is configured, which the seat device laterally trough-shaped surrounds. Sample receiving device according to one of the claims 1 to 4, wherein the rinsing device is a rinsing pump, in particular a peristaltic rinsing pump. Sample receiving device according to one of the claims 1 to 5, comprising one with the sample receiving needle and with the Sample loop coupled dosing device for dosing the sample. A sample receiving device according to claim 6, wherein the Metering device is set up, fluid sample from a sample reservoir into the sample loop. Sample receiving device according to claim 6 or 7, wherein the metering device is a piston pump, in particular a high-pressure piston pump, or has a syringe. Sample receiving device according to one of the claims 6 to 8, wherein a pumping unit of the metering device separate from a pumping unit of the rinsing device is provided. Sample receiving device according to one of the claims 1 to 9, wherein the rinsing device for rinsing after conveying the fluid sample into the sample loop and after injecting the fluid sample from the sample loop into the mobile Phase is set up. Sample receiving device according to one of the claims 1 to 10, wherein the rinsing device for rinsing before transporting the fluid sample into the sample loop and before injecting the fluid sample from the sample loop into the mobile Phase is set up. Sample receiving device according to one of the claims 1 to 11, wherein the purging device is a flushing valve wherein, by adjusting a valve position of the purge valve each one of a plurality of different rinsing solutions is selectable for rinsing. A sample receiving device according to claim 12, wherein the flush valve is controllable, the seat assembly in one first flushing a first rinse solution and in a subsequent second flushing a second To supply rinse solution, wherein the first Rinse solution has a stronger solvent power as the second rinse solution. Sample receiving device according to one of the claims 1 to 13, comprising an additional rinsing device, the for flushing the sample receiving needle an additional Rinse solution in such a way through the sample receiving needle passes through that the rinse solution flows through at least a portion of the sample receiving needle through the sample receiving needle exit. Sample receiving device according to one of the claims 1-14, comprising an injection valve for adjusting fluid communication properties. Sample receiving device according to one of the claims 1 to 15, pressure-resistant for operation at a pressure of up to 100 bar, in particular for operation at a pressure of up to to 500 bar, in particular for operation at a pressure of up to 1000 bar and more. Measuring device for examining a fluid sample, wherein the measuring device comprises a sample receiving device according to one of claims 1 to 16 for receiving the fluid sample for injecting into the meter. A meter according to claim 17, comprising a Pump for conveying the injected fluid sample together with a mobile phase through at least part of the meter. A meter according to claim 17 or 18, comprising a separating element, in particular a separating column, for separating different fractions of the injected fluid sample. Measuring device according to one of the claims 17 to 19, set up as one of the group consisting of one Microfluidic measuring device, a liquid chromatography device and an HPLC. Method for operating a sample receiving device for receiving a fluid sample, the method comprising solvable Receiving a sample receiving needle in a seat device, wherein the sample receiving needle with a sample loop for receiving a Sample volume is connected; Moving out of the sampling needle from the seat assembly to the fluid sample in the sample loop record; Apply a rinse solution in an at least partially moved out of the seat assembly Sampling needle, so that the rinse solution through the seating device at least partially exits.