WO2004111633A1 - Procedes et appareils d'echantillonnage - Google Patents

Procedes et appareils d'echantillonnage Download PDF

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Publication number
WO2004111633A1
WO2004111633A1 PCT/GB2004/002560 GB2004002560W WO2004111633A1 WO 2004111633 A1 WO2004111633 A1 WO 2004111633A1 GB 2004002560 W GB2004002560 W GB 2004002560W WO 2004111633 A1 WO2004111633 A1 WO 2004111633A1
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WO
WIPO (PCT)
Prior art keywords
valve
sample
detector
arrangement
chromatography
Prior art date
Application number
PCT/GB2004/002560
Other languages
English (en)
Inventor
Mark Jones
Niels Waleson
Mark Portsmouth
Original Assignee
Combipure Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Combipure Ltd filed Critical Combipure Ltd
Publication of WO2004111633A1 publication Critical patent/WO2004111633A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/62—Detectors specially adapted therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/80—Fraction collectors
    • G01N30/82—Automatic means therefor

Definitions

  • the present invention relates to apparatus and methods for use in chromatography, and in particular to sampling apparatus and methods allowing a sample of a main sample stream to be obtained.
  • Chromatography is a well known method which can be used to separate a mixture into component parts.
  • chromatography can be used to help, analyse the components of a mixture, e.g. in terms of their relative abundance and/or chemical composition, or to help purify a mixture, e.g. by separating out a single target component.
  • Detectors are often used as part of a chromatography based process, in order to determine properties of the components that have been separated out or to determine quantities of them.
  • Some chromatography systems can provide a constant supply of some of the sample stream to a detector.
  • the line can become blocked or at least partially blocked, further reducing the amount of sample available to the detector for detection.
  • the accuracy and reliability of detection can be poor in such systems.
  • some detectors tend to need a high sensitivity as often the likely amount of a component to be measured is unknown before hand and often very small, trace amounts of components or impurities can be present in a sample. There can also be difficulties in ensuring that a detector is not saturated by a sample or indeed damaged by having too large a sample presented to it, for example, by flooding a detector with solvent.
  • the present invention therefore provides apparatus and methods by which samples of a sample undergoing chromatographic processing can be obtained to provide reliable and accurate measurements
  • a sampling arrangement for use in a fluid chromatography system, the arrangement comprising a valve having an input, a first output and a second output, the input receiving a sample stream from a chromatography device, and the valve being operable to occasionally divert a portion of the sample stream to the second output to provide an input for a detector.
  • the valve diverts a sample from a main sample stream passing through the valve so that it can be provided as input to a detector, but not continuously. Hence, larger amounts of components in the sample stream can be directed to the detector allowing more accurate and reliable measurements of any components in the sample.
  • the valve is operable to divert a portion of the whole of the sample stream.
  • the valve can be configured so that all of the sample stream is occasionally diverted for a time toward the detector.
  • the sampling arrangement can further comprise a pressure regulator in fluid communication with the second output of the valve and actuable to substantially prevent the detector from being exposed to a fluid pressure above a selected pressure.
  • the pressure regulator can make sure that the sample is only presented to the detector if the fluid pressure is less than that which would saturate, overwhelm or damage the detector.
  • the valve can be controllable by a control signal.
  • the control signal can be electronic, pneumatic or hydraulic.
  • the valve is an electronically actuable valve, and more preferably the valve is a solenoid valve.
  • other types of valve which can be actuated or operated by an electronic control signal can be used.
  • the arrangement can include a controller.
  • the controller can be in communication with the valve to control sampling.
  • the controller can control the duration and/or the period or frequency of the sampling by the valve.
  • the controller can be a valve timing controller.
  • the controller can includes a memory for storing a time table defining sampling events. The time table can determine the duration of sampling and the frequency of sampling.
  • the pressure regulator can be any device which can prevent a connected detector from being exposed to a fluid pressure in excess of a threshold or safe pressure.
  • the pressure regulator can be pressure actuable. In this way, the pressure regulator does not require any control signals and can be considered to be a passive component as its operation is determined by the fluid pressure in the regulator at any time.
  • the pressure regulator can be an active component, in that a control signal is applied to the pressure regulator to cause it to actuate.
  • the pressure regulator can include a valve, and preferably the pressure regulator can include a pressure relief valve.
  • the pressure relief valve can be a passive device or an active device.
  • the relief valve can be sample fluid pressure actuable or electronically actuable.
  • the fluid can be a gas or is preferably a liquid.
  • An output port of the valve can be connected by a conduit to a detector.
  • the detector can be any device that can detect the property of a component of a sample.
  • the detector can be any detector device that operates by means of a spray chamber or nebulizer, rather than by means of a flow-through cell, and can include detectors that are solvent flow limited. Examples of suitable detectors would include, a light scatter detector, a chemiluminescence detector, a nitrogen detector or an atomic emission detector.
  • the property is the mass of a component.
  • the detector is a mass spectrometer.
  • a chromatography apparatus including a chromatography device and the arrangement according to the first aspect of the invention.
  • the sampling apparatus can be provided in a chromatography system at any location relative to a chromatography apparatus at which a sample of the main sample stream can usefully be acquired.
  • the arrangement can be upstream of a chromatography device.
  • the chromatography device is upstream of the arrangement.
  • a liquid chromatography mass spectrometer (LCMS) system including an arrangement according to the first aspect of the invention.
  • a method for sampling a sample stream in a fluid chromatography apparatus comprising occasionally diverting a portion of the sample stream into a conduit in communication with a detector.
  • the method comprises diverting the whole of the sample stream for a period of time.
  • a sample is not continuously diverted.
  • diverting a sample includes occasionally, and more preferably periodically, diverting samples from the sample stream.
  • Periodically diverting samples can include applying a periodic control signal to a valve.
  • the method can further comprise passing the portion of the sample stream to the detector if the fluid pressure that the detector would be exposed to is less than a selected pressure and not passing all of the portion of the sample stream to the detector if the fluid pressure that the detector would be exposed to is greater than the selected pressure.
  • sufficient of the sample is removed from the conduit so that the resulting fluid pressure that the detector would be exposed to is less than the selected pressure.
  • the whole of the sample can be removed and not passed to the detector. Removing the sample can include actuating a pressure regulator.
  • a method for isolating or purifying a sample using chromatography apparatus comprising running the sample through a chromatography device and sampling the sample according to the method of the preceding aspect of the invention.
  • the method can further comprise measuring a property of the sample using the detector.
  • the property is mass
  • the detector is a mass spectrometer.
  • Figure 1 shows a schematic block diagram of a chromatography system including a sampling arrangement according to the invention
  • Figures IA and IB show schematic diagrams illustrating a sample introducing part of the system of figure 1;
  • Figure 2 show a schematic block diagram of an embodiment of a sampling arrangement according to the invention
  • Figure 3 shows a flow chart illustrating at a high level a method of operation of the system shown in Figure 1;
  • Figure 4 shows a flow chart illustrating in greater detail a first part of the method illustrated in Figure 3;
  • Figure 5 shows a flow chart illustrating in greater detail a second part of the method illustrated in Figure 3;
  • Figure 6 shows a flow chart illustrating operations carried out by a computer control system and corresponding generally to the method illustrated in Figure 4;
  • Figure 7 shows a flow chart illustrating operations carried out by a computer control system and corresponding generally to the method illustrated in Figure 5.
  • a chromatography system generally designated 100, according to the present invention and operating according to a method aspect of the invention.
  • the chromatography system and method can be used in the general investigation or analysis of samples of chemical compounds and are particularly suited for use in the isolation of components of a sample or the purification of a sample, e.g. in order to extract a particular target chemical compound.
  • the system and method are particularly suited for use in purifying samples as part of a drug discovery program, but are not limited to that particular application.
  • the range of application of the system 100 and principles underlying the method of operation of the system will be apparent to a person of ordinary skill in the art in light of the following discussion of the general principles underlying the invention.
  • Chromatography system 100 includes a chromatography subsystem 102 comprising various chromatography related parts, apparatus and detectors, i.e. the 'wet chemistry' parts of the system, together with an electronic control subsystem 104.
  • the chromatography subsystem includes a pumping system 106, including first 106 A and secodn 106B pumps, which are connected by tubing to a source of solvent, or eluent, for use during a chromatography run.
  • a suitable pump for pumps 106 A and 106B would be a PU-2086 model available from Jasco (UK) Ltd.
  • the solvent can comprise an aqueous solution of an organic liquid and can include separate sources of water 108 and the organic component 110. Examples of suitable organic components would include, acetonitrile and methanol.
  • the outputs of pumps 106A, 106B are connected via a mixer 107 and can be used to carry out a gradient chromatography method in which the proportion of organic component in the solvent stream passing through the chromatography column is increased during the chromatography run.
  • Gradient chromatography methods are well known to persons of ordinary skill in the art and will not be described in further detail herein.
  • the output of pumping system 106 is connected by a length of tubing to a sample introduction part 112 of the system.
  • the sample introduction part 112 includes a valve 116 to which the pumps are connected via a first input port.
  • the sample introduction part 112 also includes an injector port 114 into which a sample can be injected.
  • a sample loop 118 is connected across a third and fourth port of the valve.
  • the valve 116 has a waste output port connected to a length of tubing providing a waste line 122, and a further main output port 120.
  • valve 116 actuable in use to provide to modes of operation.
  • a first loading mode shown in Figure IA the sample loop is connected to the injection port 114 and waste line 122 and the pump and a chromatography column are connected. Hence a sample can be injected into sample loop 118.
  • a second injection mode shown in Figure IB the sample loop is connected to the pump line and the chromatography column so that the sample can be introduced into the eluent stream, and the injection port is connected to the waste line.
  • a suitable sample injector device is the 215 model as provided by Gilson Inc.
  • the main output port 120 of valve 116 is connected to a chromatography column 124 which provides a chromatography device allowing different components of a sample to be separated based on their relative affinities for the column.
  • a suitable chromatography column is the Genesis model as provided by Argonaut Technologies, Inc. That column is approximately 150 mm long with an internal diameter of approximately 10 mm and is packed with 7 micron silica micro-spheres which provide the chromatography medium.
  • the details of the chromatography device will depend on the application of the system, the sample compounds and the performance required.
  • the output of the chromatography column 124 is connected by a further length of tubing to a UV detector 128.
  • a suitable UV detector is the MWD device as provided by Agilent, Inc.
  • the UV detector is provided mainly for diagnostic purposes, i.e. to monitor the column performance.
  • the UV detector could also be used to trigger component collection, either alone or in conjunction with the mass spectrometer to be described below.
  • the UV detector 128 is provided downstream of the chromatography column and in use receives the separated components of the sample in sequence. The different components of the sample are removed from the chromatography column as the concentration of the organic component in the eluent increases.
  • An input port of a second valve 130 is connected by a length of tubing to an output of the UV detector and is provided downstream of the chromatography column 124 and UV detector 128.
  • a first output port of valve 130 is connected by a third length of tubing, including a T-junction 131, to a pressure controlling or regulating device 132.
  • the output of the pressure regulator 132 has a length of tubing connected to it providing a further waste line 136.
  • the third limb of the T-junction is connected by a length of tubing to an input of a mass spectrometer 134.
  • a suitable mass spectrometer is a G 1946 as provided by Agilent Inc.
  • Mass spectrometer 134 provides a detector which can detect and measure the masses of the components of the sample.
  • valve 130 is actuated to divert a sample of the main sample stream toward the mass spectrometer 134, and pressure regulator 132 ensures that the mass spectrometer is not exposed to a fluid pressure likely to over load or cause damage to the mass spectrometer.
  • Sampling arrangement 138 will be described in greater detail with reference to figure 2 below.
  • a further output port of valve 130 is connected by a line of tubing to an input of a third valve 140.
  • a first output of valve 140 has a line of tubing attached thereto providing an output line 142 from which an isolated component or components can be collected.
  • a second output of valve 140 has a further section of tubing attached thereto providing a waste line 144.
  • a suitable valve for valves 130 and 140 is a 3 -way solenoid controlled, isolation valve, such as the 100T3 model as provided by Bio-Chem Valve, Inc.
  • the chromatography and detector parts of the chromatography subsystem 102 are controlled by the electronic control subsystem 104.
  • the control subsystem includes a computer 150, such as a conventional personal computer, including a data processing device and primary and secondary storage devices as will be apparent to person of ordinary skill in the art.
  • the dashed lines indicate control lines along which control signals and/or data can be transmitted between the control subsystem 104 and the parts of the chromatography subsystem.
  • Computer 150 has a network device 152 in communication therewith providing a local network over which data and control instructions can be transmitted to various parts of the chromatography system.
  • Pump 106 is connected by a serial communication line to a serial interface of computer 150.
  • the sample injector is also connected by a serial communication line to a serial interface of computer 150 (not shown).
  • UV detector 128 and mass spectrometer 134 are in communication with the computer 150 over network 152.
  • the control subsystem also includes a controller 154 for controlling the timing of various events during operation of the system as will be described in greater detail below.
  • controller 154 is connected to the network 152 and includes control lines to communicate signals to and from valves 116, 130 and 140.
  • valve 116 will be referred to as the sample or injection valve
  • valve 130 will be referred to as the sampling valve
  • valve 140 will be referred to as the collection or output valve.
  • sampling arrangement 138 includes the sampling valve 130 and the pressure monitor or regulator 132.
  • sampling valve 130 is a solenoid valve.
  • the valve When a gate signal is applied to the solenoid 152, the valve is actuated to connect the input 154 to the first output 156 so as to pass a part of the sample stream toward the mass spectrometer 134.
  • the sampling valve In the absence of a gating signal applied to solenoid 152, the sampling valve passes the sample stream from input 154 to output 158.
  • the pressure regulator 132 is configured to prevent the mass spectrometer from being exposed to a fluid pressure sufficiently large to damage the mass spectrometer. There are a number of mechanisms by which this can be accomplished.
  • the pressure regulator 132 is provided by a two port pressure relief valve 172. If the fluid pressure experienced by the valve 172 exceeds the selected safe threshold level for the mass spectrometer 134, then the pressure release valve is actuated, under action of the sample fluid pressure, and the sample is passed to the waste line 136 and ejected, thereby reducing the fluid pressure to which the mass spectrometer would otherwise experience at T-junction 131.
  • a suitable pressure relief valve is the 075RV model as provided by Bio-Chem Valve, Inc. This pressure release valve operates at approximately 20 psi and hence will prevent the mass spectrometer 134 from being exposed to fluid pressures in excess of 20 psi.
  • other pressure thresholds can be used depending on the detector device.
  • the pressure regulator 132 acts to reduce the flow rate of solvent to the mass spectrometer.
  • the sampling valve sprays the whole of the sample stream into tube 160 and the fluid flow rate is mainly determined by the amount of time for which the sampling valve is 'open' and diverting the sample stream into conduit 160. Diverting a part of the whole of the sample stream on an occasional basis, provides a more accurate and reliable component detection by the mass spectrometer an is not affected by gradient changes during a run. Further, it helps to avoid blockages forming in the tubing which changes the impedance of the tubing thereby reducing the reliability and accuracy of the mass spectrometer measurements. Further more, it is easy to control the rate of fluid flow to the mass spectrometer by simply changing the time for which the sampling valve is open to divert the sample stream.
  • pressure regulation merely means that the device prevents the mass spectrometer connected downstream of it from being exposed to a pressure in excess of a safe pressure value. It does not mean that a fluid sample must be supplied to the mass spectrometer at a specific or fixed level.
  • the pressure regulator 132 could include a solenoid valve and a pressure sensor to detect the pressure that the mass spectrometer is being exposed to and to actuate the solenoid valve to redirect fluid to waste if the pressure exceeds the safe pressure threshold value.
  • the sampling arrangement 138 provides a simple mechanism to ensure that a detector device attached to it is not exposed to a fluid pressure likely to damage the device.
  • the use of the sampling arrangement is not limited to use with a mass spectrometer 134 but can be used with any detector or device which is pressure sensitive and which can be used in as a detector in a chromatography system. Further, use of the sampling arrangement is not considered to be limited to the specific chromatography system shown in figure 1 and that other applications of the sampling device in chromatography systems will be apparent to persons of ordinary skill in the art in light of the foregoing.
  • FIG 3 there is shown a flowchart 300 illustrating at a high level, a method of operation of the system shown in figure 1 according to an aspect of the invention.
  • a first, pre-screen, chromatography run is carried out at step 302 using a portion of the sample in order to determine a time window during which a target component of the sample of interest would be available for collection at the output of the chromatography system.
  • a second, preparation, chromatography run is then carried out using the remainder of the sample and the target compound of interest is then collected during the collection window as determined in the previous run.
  • the mass spectrometer is used only during the pre-screen run and does not need to be used during the second preparation run.
  • FIG. 4 shows a flowchart 308 illustrating operations carried out during the first step of method 300 and corresponds generally to method step 302.
  • a first step 310 the sample to be analysed is prepared, by dissolving the chemical sample to provide a solution for use in the chromatography runs.
  • a suitable solvent is dichloromethane.
  • Approximately 5 microlitres of the sample solution is used for injection in the first run.
  • the sample is injected into the sample loop 118.
  • the UV detector 128 and mass spectrometer 134 are started, a gradient run is initiated by starting the pump system 106.
  • valve 116 is actuated to connect the sample loop 118 into the eluent stream and the sample stream carries the sample into chromatography column 124.
  • the initial components of the sample leave the chromatography column 124 and pass through detector 128 where the components are detected for mainly diagnostic purposes.
  • the UV detector can be used to monitor the progress of the separation or column performance and typically responds to all components of a sample, some of which may not be detected by the mass spectrometer.
  • the components then pass through sampling valve 130 which is periodically actuated at step 320 so as to obtain a small portion, or sample, of the main sample stream and which is directed toward mass spectrometer 134.
  • the amount of the sample can easily controlled by varying the sampling frequency and duration of the sample.
  • the sample of the main sample stream is passed through pressure regulator 132 to the mass spectrometer 134 where any component in the sample of the sample stream is detected and measured by the mass spectrometer.
  • the output valve 140 connects the sample stream to waste line 144 and the sample stream is run off to waste as indicated by step 322.
  • the proportion of organic component in the eluent is increased and the components of the sample are sequentially removed from the chromatography column.
  • the components pass through the system and a sample of the components is diverted to the mass spectrometer on a periodic basis, e.g., once every second.
  • the mass spectrometer 132 will have recorded data indicative of the start time and the stop time of the first, pre-screen, chromatography run and the mass of the components detected during that run, and the time at which those components were detected in the sample stream. Knowing the time at which a component corresponding to a target component of interest, e.g. a pharmaceutical compound to be isolated, it can be determined at what time the component would be present at the output of the chromatography system for collection. Based on this retention time of the target component, i.e. the time from the beginning of the run after which the target component would be available for collection, a window of time extending slightly before and slightly after the retention time can be determined and used in a second run to collect the target component only.
  • a target component of interest e.g. a pharmaceutical compound to be isolated
  • Figure 5 shows a flowchart 330 illustrating various operations carried out during the second, preparative chromatography run and corresponding generally to method step 304 of figure 3.
  • the remainder of the sample solution is used and all, or most, of the remaining sample solution is then injected into sample loop 118 at step 334.
  • the second preparative chromatography run is begun and pump 106 is started together with the UV detector and mass spectrometer 134.
  • Valve 116 is also operated to pass the eluent stream through sample loop 118 so as to introduce the sample into the main chromatography sample stream.
  • Sampling valve 130 does not need to be periodically activated during this second run, but merely connects directly to the output valve 140 as indicated by method step 338.
  • Sampling valve 130 can be considered to be 'open' from the perspective of the collection valve 140.
  • valve 140 Up to the beginning of the collection window, valve 140 is actuated to connect to the waste line 144 and the eluent and any non-target components of the sample are run off to waste 340.
  • collection valve 140 At the time corresponding to the beginning of the collection window, collection valve 140 is actuated to connect the sample stream to the product collection line 142 and the target component is collected at step 342.
  • collection valve 140 is actuated again to connect the sample stream to waste line 144 and the remainder of the sample stream can be run off to waste at step 344.
  • the apparatus and method are particularly suited for use in purification of a sample, i.e., to extract a single target component having a particular mass from a sample.
  • the system and method can be used to isolate different target components from the same sample by determining temporally separated collection windows for each of the target components present in the initial sample. The collection valve 140 is then operated for each collection window in order to allow the target components to be collected in different receptacles.
  • Figure 6 shows a flowchart 350 illustrating operations carried from the perspective of the control subsystem 104 during the first chromatography run.
  • computer 150 can send and receive control signals to various components of the chromatography subsystem 102 and transmit and receive data to and from the components of the chromatography subsystem.
  • Computer 150 can control pump 106 and injector 114 over serial communication lines.
  • Valve 116, sampling valve 130 and collection valve 140 are all connected to a controller 154 which communicates with computer 150 over network 152.
  • Controller 154 includes a microcontroller having a microprocessor together with local memory for storing instructions to control operation of the controller and to store data representing a timetable of events and control signals to be issued to the valves corresponding to those events.
  • the UV detector 128 and mass spectrometer 134 can also include onboard control systems including microprocessor devices and memories into which control and timetable data can be downloaded over network 152 by computer 150. UV detector 128 and mass spectrometer 134 can record and store data locally during operation and subsequently upload the detector experimental data to computer 150 over network 152 for subsequent processing and analysis.
  • step 352 prior to beginning the first pre-screen run, computer 150 downloads timetables to the timing controller 154, pump 106, UV detector 128 and mass spectrometer 134.
  • the timetables include data indicating sequences of events and the timing of those events to be carried out by the devices.
  • the pump, detectors and valves are also initiated during step 352.
  • the pre-screen run is begun.
  • the UV detector 128 detects the intial components as they are released from the chromatography column and, knowing the start time of the chromatography run, records measured data from the UV detector as a function of the time of detection of the various components.
  • the timing controller 154 knows the start time of the chromatography run and when its internal clock determines that the delay has expired (e.g. after 0.5 minutes) then the controller inspects the timetable data to determine a duration for a gating signal and a period for the frequency of applying that gating signal to the solenoid 152 of the sampling valve 130.
  • the timetable also includes an indication of the duration of time during which the gating signal is periodically applied to the solenoid of the sampling valve 130.
  • the duration of the gating signal can be 40 milliseconds and the gating signal can be applied once every minute up until between three to five minutes after expiry of the initial delay.
  • a gate signal is applied to the solenoid of sampling valve 130 which directs a sample of the main sample stream to mass spectrometer 134 for 40ms.
  • Valve 130 then reconnects to collection valve 140 for 960ms until the next gating pulse is applied.
  • the gating pulse is periodically applied until it is determined at step 360 that the sampling time has expired.
  • mass spectrometer 134 Provided the fluid pressure of the sampled part of the sample stream does not exceed the safety pressure threshold for the mass spectrometer 134, then pressure regulator 132 is not actuated and the sample is passed to mass spectrometer 134.
  • the mass spectrometer knows the start time of the sample run, the elapsed time and determines the mass of any components detected in the sample and the time of detection of the components.
  • the timetables indicate to each component to cease operation and the chromatography run completes at step 362.
  • the UV experimental data can then be transferred over the network 152 and stored on computer 150 and similarly with the mass spectrometer experimental data.
  • a collection window or windows are determined for each target component or components of interest. The total ion current from the mass spectrometer is integrated and the centre of the peaks for each component is identified to provide a retention time for that component. The retention time so determined corresponds to the time at which the mass spectrometer actually detected the component.
  • any time offsets (positive or negative) to account for the fact that the component of interest may be received at collection valve 140 at a time before or after the component was actually detected by the mass spectrometer (e.g. because of different fluid path lengths) are then determined.
  • the start and end times for a collection window spanning the corrected retention time is then determined.
  • the centre of the total ion current peak for that component is determined and may be e.g. 3.5 minutes. That component may be expected to arrive at the collection valve 140 approximately 0.1 minutes before the component would be detected by the mass spectrometer, e.g. as the fluid path to the collector valve is shorter, and therefore the corrected retention time would be 3.4 minutes.
  • FIG. 7 shows a flowchart 370 illustrating operations carried out by the control subsystem 104 during the second preparative chromatography run.
  • timetable data is downloaded to the timing controller 154 and also to pump 106 in order to carry out a gradient chromatography run substantially identical to the run used during the pre-screen run.
  • valve timing controller 154 applies a control signal to the solenoid of collection valve 140 to 'open' valve 140 to direct the sample stream to collection line 142 for collection in a receptacle.
  • the second preparative chromatography ran can then be ended at step 382.

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Abstract

L'invention concerne un ensemble d'échantillonnage et un procédé destiné à être utiliser dans un système de chromatographie en phase liquide. Ledit ensemble d'échantillonnage comprend une buse présentant une entrée, une première sortie et une seconde sortie. L'entrée reçoit un flux d'échantillons à partir d'un dispositif de chromatographie, et la buse peut fonctionner pour dévier occasionnellement une partie du flux d'échantillon vers la seconde sortie, de manière à fournir une entrée pour un détecteur. Un régulateur de pression peut être également utilisé, de manière à réguler la pression du liquide, auquel le détecteur est exposé. Ledit procédé comprend la déviation occasionnelle d'une partie du flux d'échantillon dans un conduit en communication avec le détecteur.
PCT/GB2004/002560 2003-06-13 2004-06-14 Procedes et appareils d'echantillonnage WO2004111633A1 (fr)

Applications Claiming Priority (2)

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GB0313728.8 2003-06-13
GB0313728A GB0313728D0 (en) 2003-06-13 2003-06-13 Sampling methods and apparatus

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WO2004111633A1 true WO2004111633A1 (fr) 2004-12-23

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000026662A1 (fr) * 1998-10-30 2000-05-11 Ontogen Corporation Dispositif et technique de purification multicanal a debit eleve

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000026662A1 (fr) * 1998-10-30 2000-05-11 Ontogen Corporation Dispositif et technique de purification multicanal a debit eleve

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