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WO2006000840A1 - Systeme de purification de chromatographie - Google Patents

Systeme de purification de chromatographie Download PDF

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Publication number
WO2006000840A1
WO2006000840A1 PCT/HU2005/000068 HU2005000068W WO2006000840A1 WO 2006000840 A1 WO2006000840 A1 WO 2006000840A1 HU 2005000068 W HU2005000068 W HU 2005000068W WO 2006000840 A1 WO2006000840 A1 WO 2006000840A1
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WO
WIPO (PCT)
Prior art keywords
fraction
sample
component
collecting
selector
Prior art date
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Ceased
Application number
PCT/HU2005/000068
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English (en)
Inventor
Ferenc Darvas
Lajos GÖDÖRHÁZY
Tamás KARANCSI
Dániel SZALAY
László ÜRGE
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
AMRI Hungary Zrt
Original Assignee
Comgenex RT
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Filing date
Publication date
Application filed by Comgenex RT filed Critical Comgenex RT
Publication of WO2006000840A1 publication Critical patent/WO2006000840A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • G01N30/80—Fraction collectors
    • G01N30/82—Automatic means therefor

Definitions

  • the present invention relates to a chromatography purification system for automatically separating different components in a sample to be purified and for collecting the fraction of at least one target component.
  • a chromatography purification process comprises the following basic steps: 1. separation of the components of a sample through chromatography and detection of the various components, for example, by means of an UV detector or a mass spectrometer; 2. collection of the separated components; 3. follow-up analysis of the collected fractions for determining purity or molecule masses of the components for identifying the desired component, which is the so called target component; 4. follow-up selection of the fractions of the target component and processing thereof including dry-in, reformatting, final quality control, etc.
  • a key issue in the filed of fraction collection is that the number of fractions that will be separated from a sample is not known in advance when starting a purification process.
  • prior adjustment of the conventionally used fraction collection parameters like the width of the detection window or the intensity threshold of the detection is often not enough for an exact estimation of the number of fractions deriving from a single sample, therefore capacity of the fraction collector is usually to be greatly oversized.
  • capacity of the fraction collector is usually to be greatly oversized.
  • finding the target component among the collected fractions requires a large number of follow-up analytical measurements and the follow-up selection of the desired fractions may be performed only on the basis of the measurement results. These steps require a lot of time to carry out and are rather expensive.
  • a disadvantage of this method is that the analytical measurements prior to the purification are available for the determination of the preparative chromatographic conditions only if the relationships between the critical chromatographic parameters are known in advance due to prior calibration measurements. Even in the case of providing optimal chromatographic conditions for each sample, it is not guaranteed to collect only one fraction.
  • Another disadvantage of this method is that the narrower the retention time window is, the greater likelihood it has that, because of the accumulated timing errors of the optimizing algorithm, the component to be purified slides out from the retention time window.
  • Another technique also used wide-spread is to minimize the number of fractions by a fraction collection process controlled by a structure identifying detection method.
  • a structure identifying detection method is disclosed, for example, in J.P. Kiplinger et al. "Rapid Communications on Mass Spectrometry” (1998, Vol. 12, p. 658).
  • This detection technique is based on the recognition of occurrence of the molecule mass of the chemical component to be purified among the peaks of the chromatographically separated components when the system works in a selecting mode. Fraction collection takes place only if the desired molecule mass appears in the mass spectrum. In most cases, this technique allows to collect only one fraction during the purification of a sample.
  • a serious disadvantage of this technique is that it requires the use of a very expensive mass spectrometer.
  • a further disadvantage is that appearance of a component having the same molecule mass as that of the component to be purified causes the collection of more than one fraction from a sample, and therefore a series of follow-up analytical measurements is necessary for selecting the actually desired target component from the components having the same molecule mass.
  • Patent No. US 6,652,746 discloses an automated chromatography purification system using an UV detector.
  • the UV detector signals every chromatographic peak, thus each component of a sample is collected and dispensed by the fraction collector into different fraction containers.
  • This method is not available for determining the number of fractions in advance, and classification of the fractions, for example on the basis of the heights of the chromatographic peaks, may be carried out only by means of subsequent operations.
  • Patent No. US 6,309,541 discloses an apparatus for automated multiple channel chromatography purification, the apparatus comprising a mass spectrometer for analyzing the components associated with the chromatographic peaks detected by a UV detector.
  • the fraction collector directs the fraction of a component accepted by the analyzer into a first fraction container, whereas the fractions . of all of the other components are directed into a second fraction container.
  • One objective of the present invention is to provide an automated chromatography purification system that allows to collect the fractions of a predetermined number of components with a predetermined property.
  • Another objective of the present invention is to provide an automated chromatography purification system that collects a low number of, for example exactly one, fraction from a sample with substantially less expense than prior art systems do it.
  • the chromatography purification system comprises a fluid streaming unit, a chromatography column for receiving a sample and separating the components of the sample, a sample injection valve for injecting the sample, a detector connected to the chromatography column for receiving the sample and outputting a signal indicating the presence of at least one component in the sample flowing through it, a waste reservoir, a fraction collector for dispensing the collected fractions into fraction containers and a system controller for controlling the operation of the fluid streaming unit and the fraction collector.
  • the system further comprises a selector for receiving the sample from the detector, selecting a predetermined number of target components with a predetermined property from the at least one component of the sample, directing the fraction of the at least one selected target component to the fraction collector and discharging the remaining part of the sample into the waste reservoir.
  • the selector preferably comprises a buffering means having a liquid buffer adapted to buffer at least one fraction, and a controller comprising a decision making algorithm for selecting the predetermined number of target components from the components in the sample, wherein the controller is adapted to control the buffering means based on a signal received from the detector and a decision of the decision making algorithm.
  • the buffering means consists of at least one two-state six-port fraction collecting valve provided with a collecting loop, wherein each fraction collecting valve is adapted to buffer the fraction of one target component in its collecting loop.
  • the controller of the selector is preferably adapted to set the at least one fraction collecting valve into an initial position or collecting position based on the signal received from the detector and the decision of the decision making algorithm.
  • the buffering means may consist of at least two fraction collecting valves that are cascaded so that the waste discharging port of each fraction collecting valve except the last fraction collecting valve is connected to the sample injection port of the succeeding fraction collecting valve, the waste discharging port of the last fraction collecting valve is connected to the waste reservoir and the sample injection port of the first fraction collecting valve is connected to the detector.
  • the selector may be in the form of an analyzer used to recognize the presence of a predetermined property.
  • the selector is preferably adapted to select the fraction of one component from the sample, the component being associated with the highest chromatographic peak.
  • the selector may be adapted to select the fractions of a plurality of components from the sample as well, for example the components associated with the highest chromatographic peaks.
  • the number of the fractions collected from a sample resulted from the purification process may be defined in advance, therefore capacity of the fraction collector may also be exactly scaled. Since at the end of the purification process only the fraction(s) of the one or more target component will be collected, there is no need of follow-up analysis and selection of fractions, which allows to save substantial time and cost.
  • FIG. 1 is a schematic block diagram of the chromatography purification system according to the invention
  • FIG. 2 schematically illustrates, in two different positions, the structure of a six-port, two-state fraction collecting valve used in the selector of the system, according to an embodiment of the invention
  • - Figure 3a-d show three cascaded fraction collecting valves of the selector adapted for collecting three fractions from a sample when fractions associated with the three highest peaks are to be collected, according to an embodiment of the invention.
  • FIG 1 the schematic block diagram of the chromatography purification system 10 is illustrated.
  • the chromatography purification system 10 comprises a fluid streaming unit 11, such as a pump, a sample inputting or injection valve 18, a chromatography column 12, a detector 14, a fraction collector 16, a reservoir 17 for waste, a system controller 20 and a selector 22.
  • the selector 22 comprises a controller 24 and at least one fraction collecting valve 30.
  • bold arrows represent the flowing path of the solution (or sample)
  • hair-line arrows represent the communication lines between the various devices.
  • the chromatography column 12 is adapted to receive the sample inputted through the injection valve 18 and separate the different components of the sample.
  • the Merck's Purospher STAR RP- 18e may be used as chromatography column.
  • the solvent flowing out from the chromatography column 12 (also called as chromatographic eluent) passes the detector 14 that regularly sends a signal to the selector 22. A particular change in the signal indicates that one of the components of the sample just leaves the chromatography column 12.
  • the detector 14 is preferably an UV detector, although the use of other kind of detectors, such as a mass spectrometer, is also feasible.
  • the selector 22 recognizes the chromatographic peaks associated with the components flowing out from the chromatography column 12, and based on a decision making algorithm, the chromatographic peaks so recognized are either collected or discharged into a waste reservoir.
  • the selector 22 preferably comprises a liquid buffer for temporary storing one or more fraction, the liquid buffer being preferably in the form of a suitably sized tube or reservoir. If the purification process addresses the separation of only one component's fraction, it is enough to use a single liquid buffer in the selector 22.
  • the selector 22 directs the one or more collected fraction to the robotic fraction collector 16 that dispenses the fractions into the respective fraction containers.
  • a chromatography purification system is introduced that is adapted to collect one component with the highest chromatographic peak as a target component from the sample to be purified. It should be noted that such a purification process is feasible only if the target component has the highest concentration with respect to all components. This condition is generally satisfied due to the aim of chromatography purification.
  • the peaks are monitored by the selector 22 according to the signals of the UV detector. In case of detecting a peak, the selector 22 decides whether the recent chromatographic peak is higher than that of the component buffered in the liquid buffer of the selector 22, wherein the comparison is performed by the controller 24 of the selector 22. If the peak associated with the recent component is higher than that of the component buffered in the liquid buffer, the selector 22 will direct the buffered fraction from the liquid buffer 'into the waste reservoir 17 and feed the fraction of the recent component into the place of the discharged fraction. Otherwise, if the peak associated with the recent component is not higher than that of the component buffered in the liquid buffer, the recent fraction will be discharged and the previously buffered fraction will further remain in the liquid buffer. It is obvious that the fraction of the first component is automatically fed into the liquid buffer since the liquid buffer is empty at the detection of the first peak.
  • the following parameters are to be set: 1. Detection threshold. The height of the peak is not measured if it is lower than this value. The fractions belonging to peaks lower than the detection threshold are automatically discharged into the waste reservoir. 2. Delay of the delaying loop. This value is a sum of at least the processing time period of the system controller, time period required by decision making process of the 5 000068
  • volume of the liquid buffer This value is defined by the expected volume of the target component.
  • the delay of the delaying loop and the volume of the liquid buffer are determined by the flow rate and the volume of the sample.
  • the fraction collecting process i.e. separation of the fraction of each component, is performed by means of a common two-state, six-port fraction collecting valve 30 widely used in chromatographic injection of samples.
  • the structure of this fraction collecting valve 30 is shown in Figure 2 in a schematic cross-sectional view.
  • the fraction collecting valve 30 in Figure 2 has two positions: an initial position A for discharging waste and a collecting position B for fraction collection.
  • the fraction collecting valve 30 comprises six ports 1 to 6 and a collecting loop 34. Rotation of the fraction collecting valve 30 into its corresponding position is controlled by the selector's controller that comprises a particular computer program for it.
  • the sample flowing out from the detector is fed into the fraction collecting valve 30 through a sample injection port 4, and the waste is discharged into the waste reservoir through a waste discharging port 5.
  • the collecting loop 34 extends between ports 3 and 6.
  • the fraction of the target component is directed to the fraction collector through port 2 of the fraction collecting valve 30 in such a way that a sufficient amount of solvent is fed into the collecting loop 34 by means of an injection pump connected to port 1, while pushing out the previously buffered fraction from the collecting loop 34.
  • the fraction collection process comprises the following steps.
  • the signal of the detector is continuously monitored by the selector 22 within a time window defined by relay actions (EVENT signals), wherein the timing of said relay actions may be arbitrarily set in a HPLC process.
  • the controller 24 of the selector 22 compares the height of the peak associated with the component buffered in collecting loop 34, said height value being stored in the controller 24, with the recent height value, and if the chromatographic peak of the recent component is the higher, it will rotate the fraction collecting valve 30 from the initial position A into the collecting position B and replace the previously stored height value with the recent height value.
  • the fraction collecting valve 30 While the recent component having the higher peak is being fed into the collecting loop 34 through port 4, when the fraction collecting valve 30 is in the collecting position B, the component previously buffered therein is being discharged into the waste reservoir through port 5. After the above mentioned time period, the fraction collecting valve 30 will automatically return from the collecting position B to the initial position A. The collected fraction thereafter remains in the collecting loop 34 until a component with an even higher peak is detected. Obviously, the collecting loop 34 of the fraction collecting valve 30 plays the role of a liquid buffer in this case. Due to the fixed length of the collecting loop 34, this embodiment of the system is suitable only for collecting fractions of constant volume, which feature should be considered at the development of a particular chromatography technology.
  • the fraction collecting valve 30 will be kept in its initial position A and the solution containing the recent component will be discharged into the waste reservoir through port 5.
  • the chromatographic fraction of the respective component travels down-stream in a delaying loop scaled in such a way that said component under analysis reaches port 4 of the fraction collecting valve 30 when the fraction collecting valve 30 has already been definitely in the proper position in response to the result of the decision making process.
  • the collecting loop 34 contains the main component (as target component) associated with the highest peak in the chromatogram, and this component is then directed to the fraction collector 16 in response to an instruction of the system controller 20 in order to dispense it into the respective fraction container.
  • the apparatus according to the first embodiment of the invention collects only one fraction from every sample, which is the fraction associated with the highest one of the chromatographic peaks. However, this apparatus may be extended so that it collects the fractions of a plurality of components associated with an arbitrary number of the highest peaks.
  • a selector for collecting the fractions associated with the three highest peaks is briefly introduced.
  • the selector adapted for collecting three fractions differs from the selector capable of collecting only one fraction in that instead of a single fraction collecting valve, it uses three cascaded fraction collecting valves 41, 42, 43.
  • the connection arrangement of these fraction collecting valves 41—43 is schematically shown in Figure 3.a-d.
  • each fraction collecting valve 41, 42 except the last fraction collecting valve 43 is connected to port 4 of the respective succeeding fraction collecting valve 42, 43, whereas port 5 of the last fraction collecting valve 43 is connected to the waste reservoir.
  • the fraction of the component associated with the first chromatographic peak which is the highest peak in this example, is buffered in the collecting loop of the fraction collecting valve 41.
  • the fraction of the component associated with the second chromatographic peak which is lower than the peak of the component buffered in the collecting loop of the fraction collecting valve 41, is buffered in the collecting loop of the fraction collecting valve 42 as Figure 3c shows. Since the third peak is lower than the first peak, but higher than the second peak, the fraction of the component associated with the third chromatographic peak is fed into the collecting loop of the fraction collecting valve 42 while the fraction collecting valves 41—43 are in the positions illustrated in Figure 3.d.
  • each fraction collecting valve may have a collecting loop of different volume, which allows to collect different amounts of fractions from a particular sample.
  • fractions buffered in the collecting loops are fed into the fraction collector 16 with the fraction collecting valves 41-43 being set in their initial position A.
  • ports 1 and 2 of the succeeding fraction collecting valves 41-43 are also connected respectively, and the fractions are directed after each other into the fraction collector.
  • fractions buffered in the collecting loops of the fraction collecting valves may be simultaneously fed into the fraction collector.
  • a selector collecting the fractions of the components associated with the three highest peak is introduced. It is obvious for those skilled in the art how the selector and its control may be extended for collecting any number of fractions by applying additional fraction collecting valves. It is also obvious that the system according to the invention is not limited to the collection of the components with the highest peaks, but it also includes systems adapted to collect components associated with the lowest peak or peaks above the detection threshold or components with other predetermined properties.
  • the selector further comprises an analyzer, thus the set of the predetermined properties may be extended, which provides even wider applicability for the system according to the invention in the field of chromatography purification.
  • the chromatography purification system provides a more rational and predictable fraction collection with respect to the prior art solutions, thus it supports elaboration of more efficient applications.
  • the use of such system guarantees that a predetermined number of component with predetermined properties, e.g. one component associated with the highest chromatographic peak, is collected from the sample under purification. This is particularly beneficial in the automated high- throughput purification processes where, for example, 96 purified fractions are to be produced from 96 samples. In these cases, identification of the fractions is unambiguous due to their positions and after the purification process, there is no need of follow-up analytical measurements or selection of the target fractions.
  • a further advantage is that the volume capacity of the fraction collector is not loaded by the accumulated set of fraction containers otherwise required to store minor fractions collected in a conventional method.
  • Yet another advantage of the system according to the invention is that in the field of the high-throughput quality control, it may be used in place of the more expensive on-line HPLC/MS technique, wherein molecule mass of the component associated with the highest chromatographic peak is determined by a follow-up mass spectrometric (MS) analysis of the collected main chromatographic components.
  • MS mass spectrometric
  • the results of the two measurements i.e. the HPLC chromatogram and the mass spectrum, characterize the sample from the point of view of its purity and its molecule mass appropriately, thus allowing a choice between the two basic outcomes of the quality control, i.e. the purity and the structural identity.
  • Due to the system according to the invention off-line detection in several HPLC systems based on mass spectrometry may be performed within substantially less time by utilizing a single mass spectrometer, taken into account the usual
  • chromatography purification system due to the chromatography purification system according to the present invention, a predetermined number of fractions with predetermined properties can be collected from each sample, therefore the number of fractions resulted from the purification process is predictable and the assignment of the fractions to the respective components is clear and unambiguous.
  • system according to the invention there is no need of preliminary analytical measurements to optimize the applied preparative chromatographic method and purification of the samples can be completed without using preliminary analytical measurement data.

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  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
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  • Treatment Of Liquids With Adsorbents In General (AREA)

Abstract

L'invention concerne un système de purification de chromatographie (10) pour une séparation chromatographique automatique d'une pluralité de composants différents d'un échantillon et pour un recueillement de la fraction d'au moins un composant cible. Ce système comprend une unité d'écoulement de fluide (11), une colonne chromatographique (12) pour recevoir un échantillon et pour séparer les composants de l'échantillon, une vanne d'injection d'échantillon (18) pour injecter l'échantillon, un détecteur (14) relié à la colonne chromatographique (12) pour recevoir l'échantillon et pour produire un signal indiquant la présence d'au moins un composant dans l'échantillon s'écoulant à travers la colonne, un réservoir de déchets (17), un collecteur de fraction (16) pour distribuer les fractions recueillies dans les contenants de fractions et un contrôleur de système (20) pour contrôler le fonctionnement de l'unité d'écoulement de fluide (11) et du collecteur de fractions (16). Le système comprend également un sélecteur (22) pour recevoir l'échantillon provenant du détecteur (14), pour sélectionner un nombre prédéterminé de composants cibles présentant une propriété prédéterminée, à partir d'au moins un composant de l'échantillon, pour diriger la fraction d'au moins un composant cible sélectionné vers le collecteur de fractions (16) et pour envoyer la partie restante de l'échantillon dans le réservoir de déchets (17).
PCT/HU2005/000068 2004-06-28 2005-06-27 Systeme de purification de chromatographie Ceased WO2006000840A1 (fr)

Applications Claiming Priority (2)

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HUP0401336 2004-06-28
HU0401336A HU225332B1 (en) 2004-06-28 2004-06-28 Chromatographic cleaner system

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WO2006000840A1 true WO2006000840A1 (fr) 2006-01-05

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10175209B2 (en) 2014-11-06 2019-01-08 Waters Technologies Corporation Liquid flow rate measurement device
WO2020074613A1 (fr) * 2018-10-11 2020-04-16 Ge Healthcare Bio-Sciences Ab Système et procédé de collecte de fractions
CN115531921A (zh) * 2022-08-26 2022-12-30 大连依利特分析仪器有限公司 一种制备型液相色谱馏分收集装置及方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020052701A1 (en) * 2000-09-08 2002-05-02 Gorenstein Marc V. Method and apparatus for determining the boundaries of a detector response profile and for controlling processes
US20020134143A1 (en) * 2001-02-27 2002-09-26 Isco, Inc. Liquid chromatographic method and system
US20020144949A1 (en) * 1999-09-16 2002-10-10 Berger Terry A. Automated sample collection in supercritical fluid chromatography

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020144949A1 (en) * 1999-09-16 2002-10-10 Berger Terry A. Automated sample collection in supercritical fluid chromatography
US20020052701A1 (en) * 2000-09-08 2002-05-02 Gorenstein Marc V. Method and apparatus for determining the boundaries of a detector response profile and for controlling processes
US20020134143A1 (en) * 2001-02-27 2002-09-26 Isco, Inc. Liquid chromatographic method and system

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
T.KATANSCI, L.GÖDÖRHAZY, D.SZALAY, F.DARVAS: "UV-triffered main-component fraction collection method and its application for high-throughput chromatographic purification of combinatorial libraries", JOURNAL OF COMBINATORIAL CHEMISTRY, vol. 7, no. 1, January 2005 (2005-01-01), pages 58 - 62, XP002340061 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10175209B2 (en) 2014-11-06 2019-01-08 Waters Technologies Corporation Liquid flow rate measurement device
GB2536749B (en) * 2014-11-06 2019-06-12 Waters Technologies Corp Liquid flow rate measurement device
WO2020074613A1 (fr) * 2018-10-11 2020-04-16 Ge Healthcare Bio-Sciences Ab Système et procédé de collecte de fractions
CN112789095A (zh) * 2018-10-11 2021-05-11 思拓凡瑞典有限公司 馏分收集系统和方法
US12318708B2 (en) 2018-10-11 2025-06-03 Cytiva Sweden Ab Fraction collection system and method
CN115531921A (zh) * 2022-08-26 2022-12-30 大连依利特分析仪器有限公司 一种制备型液相色谱馏分收集装置及方法

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HU225332B1 (en) 2006-09-28
HUP0401336A2 (en) 2006-02-28

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