WO2006021203A1 - Procede et dispositif de separation de melanges de produits - Google Patents

Procede et dispositif de separation de melanges de produits Download PDF

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Publication number
WO2006021203A1
WO2006021203A1 PCT/DE2005/001506 DE2005001506W WO2006021203A1 WO 2006021203 A1 WO2006021203 A1 WO 2006021203A1 DE 2005001506 W DE2005001506 W DE 2005001506W WO 2006021203 A1 WO2006021203 A1 WO 2006021203A1
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WO
WIPO (PCT)
Prior art keywords
column
segments
separation
dimension
substance
Prior art date
Application number
PCT/DE2005/001506
Other languages
German (de)
English (en)
Inventor
Jens-Peter MÜLLER
Dietmar Wolf
Jasmin Jakupovic
Original Assignee
Analyticon Discovery Gmbh
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 Analyticon Discovery Gmbh filed Critical Analyticon Discovery Gmbh
Publication of WO2006021203A1 publication Critical patent/WO2006021203A1/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
    • G01N30/84—Preparation of the fraction to be distributed
    • 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
    • G01N30/60—Construction of the column
    • G01N30/6052—Construction of the column body
    • G01N30/6069—Construction of the column body with compartments or bed substructure
    • 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
    • G01N30/84—Preparation of the fraction to be distributed
    • G01N2030/8411—Intermediate storage of effluent, including condensation on surface
    • 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
    • G01N30/26—Conditioning of the fluid carrier; Flow patterns
    • G01N30/38—Flow patterns
    • G01N30/46—Flow patterns using more than one column
    • G01N30/461—Flow patterns using more than one column with serial coupling of separation columns
    • 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
    • G01N30/60—Construction of the column
    • G01N30/6034—Construction of the column joining multiple columns
    • G01N30/6039—Construction of the column joining multiple columns in series

Definitions

  • the present invention relates to a process for the separation of mixtures of substances and to an apparatus for carrying out this process.
  • HPLC high pressure liquid chromatography
  • DE 38 36 343 A1 discloses a column chromatograph and a method for its operation.
  • the column chromatograph is composed of individual segments which can be decomposed after local fractionation by means of capillary chromatography. The separated mixture can then be taken from these segments together with the stationary phase.
  • the device and the method are not suitable for HPLC, since they are operated without pressure.
  • the disclosed combination column is composed of cylindrical column segments which carry threads at both ends, as well as separators which also carry threads on both sides and are provided with frits.
  • the connection of the column segments is then via this thread through which the items are firmly miteinan ⁇ screwed.
  • a connection of the column segments which can be easily detached, even in an automated method, as required by automated local fractionation, is not disclosed. The separation of the column fragments from each other must be done manually here.
  • a segment-like construction of the combination column is particularly advantageous in order to obtain columns of any but precisely defined length and column volumes.
  • the combination columns can be used as sieve cages.
  • the disclosed combination filters preferably consist of plastic and their use in high pressure liquid chromatography methods is not disclosed.
  • Object of the present invention is therefore to overcome the disadvantages of the prior art.
  • the object is achieved by a method for the separation of mixtures, wherein the separation is carried out as a local fractionation by means of HPLC technology.
  • the process is carried out in such a way that a) a mixture of substances is applied to a segmented HPLC column, b) the mixture of substances is separated by HPLC technique on the segmented HPLC column in such a way that the first substance of interest has not yet left the HPLC column and the last substance of interest is already on the HPLC column, c) the separation is stopped before the elution of the first substance, d) that on the separation material within the segmented HPLC column does not remove locally fixed substances from the HPLC column but, if necessary, couples them with further segments and carries out one or more further local distributions by means of HPLC final step is separated and isolated by fractional elution from the column material of a single segment.
  • the evaluation is carried out by means of analytical HPLC.
  • a detection method in order to obtain information about the spatial separation of the substance mixture in the separation column. It is preferred that a detector commonly used in HPLC is used for detection.
  • the detection is carried out after a subsequent separation of the substance mixture and before the separation of the separation on a further separation column.
  • Vorrich ⁇ device for carrying out the method according to the invention, wherein the device comprises separation columns 1, which consist of column segments 2.
  • the column segments 2 are detachably and movably connected to each other. Furthermore, it is preferred that the column segments 2 are connected to one another without screwing. It is also preferred that the column segments 2 are connected to one another without rapid closure.
  • the column segments 2 being connected to one another via a conical seal 6 and an inner cone 7. It is also preferable that the conical seal
  • the capillary 5 is fastened at the exit of the column segment 2 be ⁇ . It is furthermore advantageous that the inner cone 7 is located at the entrance of the column segment 2.
  • An advantageous embodiment of the device according to the invention is further that the column segments 2 are connected to each other via the located on the capillary 5 conical seal 6 of a column segment 2 with the located at the entrance of the other column segment 2 inner cone 7.
  • the compound of pressureg ⁇ elements 2 is sealed by means of an external pressure. According to the invention, this is preferably done by a pneumatic, mechanical or hydraulic element 13. It is also advantageous that the separation columns 1 consisting of column segments 2 are arranged on carriages 20. In this case, it is particularly preferred according to the invention that the carriages 20 can be moved horizontally and vertically within the device. But it is also advantageous that the carriage 20 are movable via linear technology with drive. Furthermore, it is preferred that a plurality of carriages 20 are arranged in one device and that the carriages are sprung against one another.
  • the column segments 2 be supplied with eluents via lines. It is particularly preferred that the mobile phase is pumped into the column segments 2.
  • the mobile phase flow is controlled in ⁇ nerrenz the device via valves.
  • the device according to the invention can be operated automatically. It is very particularly preferred that the application of the substance mixture to the column segments 2 is controlled automatically. However, it is also preferred that the supply of the column segments 2 with mobile phase is controlled in an automated manner. It is also particularly preferred that the valves for the control of the solvent flows are controlled automatically.
  • the compression of the column segments 2 by means of the pneumatic elements are automatically controlled. It is preferred here that the movement of the carriages 20 takes place automatically.
  • An apparatus according to the invention which is operated in a computer-controlled manner is very particularly preferred.
  • an industrial robot is integrated in the device. It is particularly preferred that the industrial robot moves the segment columns in the device.
  • the fractional fractionation is already completed shortly before the first substance of interest leaves the separation device and the last substance of interest has reached the separation device.
  • This absolutely necessary separation of the substance mixture is carried out in the process according to the invention the choice of material in the separation device, the choice of eluent and its composition, the determination of the time to completion of the local fractionation and the choice of gradients or isocrates fulfilled. It is advantageous here that all the column material, normal phase material and reverse phase material known in the prior art can be used.
  • the selection of the mobile phase or of the solvent mixture is not subject to any special requirements in the process according to the invention and depends only on the individual properties of the substance mixture. As a result, the process is not subject to any particular restrictions and can be used almost indefinitely. It is imperative, however, to carry out the chromatography under high pressure, since the process according to the invention is carried out only under HPLC
  • the individual substances of the mixture are according to their polarity on delimited areas (places) of the separator.
  • the fractionation has led to a distribution of the substances of the mixture to different locations in the separating material used along the spatial axis in the direction of the output from the separation device (separation column).
  • This first separation of the substance mixture is referred to as separation in the 1st dimension in the context of the present invention. In the first step of the process, therefore, a separation takes place along the direction of flow and the substances are spatially fi xed in the separation column without having left the separation material.
  • the inventive method can then be continued by a further separation of the spatially fixed substances or the fixed substances can be separated after separation in the 1st dimension of the separation column and isolated from the separating material.
  • the substances can be separated from the column material by standard extraction methods, they can be flushed out of the material in fractions or through
  • the substances fixed in the first dimension on the phase are selectively transferred from the eluent from the respective segment to downstream separation devices - leads.
  • the substance fractions are then subjected to a second local fractionation, which is referred to as spatial fractionation of the second dimension.
  • components of the transferred substance fraction are distributed on the second separating device according to their polarity and, after separation, are spatially fixed on the second separating device. Also in the second dimension, the separation is completed before the first fraction of the mixture leaves the separation column.
  • the separated substances can now be isolated or the process steps described above can be repeated until the substances are present in the desired purity.
  • the location fractionation can be repeated as often as desired, up to the nth dimension.
  • the substances are isolated as described above.
  • the site fractionation according to the invention is carried out using high pressure liquid chromatography.
  • an automated implementation of the method according to the invention, with high skillssatzmen ⁇ gene is possible.
  • the steps of substance application, separation, transfer of the locally fixed substances into a further separation device for local fractionation in the next dimension, detection and flushing of the substances can be carried out automatically.
  • the method can also be carried out computer and / or robot-assisted.
  • the automated transfer of the fixed-location substances into the next dimension requires a special embodiment of the chromatography columns in order to be able to dispense with manual isolation of the substance and introduction onto the separation columns of the next dimension.
  • the device according to the invention can be used, which will be described in detail below.
  • a component of the device according to the invention is a combination of separable segment columns, which replace the chromatography columns known in the prior art.
  • These chromatographic columns according to the invention consist of column segments which are coupled together.
  • the column segments are preferably combined in such a way that a chromatographic column is used which is of the same length as a conventional long HPLC column like.
  • the chromatography column filled with separating material can be broken down into the segments after a separation process has been carried out, and these segments containing substance-loaded separating material can then be used for targeted transfer of the substance into the next dimension of the fractionation or for flushing the substance ver ⁇ be used.
  • FIG. 1 shows the principle of the multidimensional spatial fractioning according to the invention.
  • the structure of a column segment is illustrated in FIG.
  • FIG. Figure 4 shows an arrangement of 25 segments for distribution in the 1st and 2nd dimension and Figure 5 illustrates a section of the segment arrangement.
  • the mechanical structure of a device according to the invention for multi-dimensional local fractionation is shown in FIG. fi
  • FIG. 7 shows the mobile phase flows in the case of a distribution in the third dimension
  • FIG. 8 illustrates a dispensing system with automated fixed bed injection.
  • FIG. 9 illustrates the combination of sample application and solvent streams in distributions.
  • the online detection in the second dimension of the spatial fractioning according to the invention is shown in FIG. 10, and FIG. 11 shows by way of example the use of industrial robots for the further automation of the device according to the invention.
  • FIG. 12 shows the principle of the known time fractionation. A mixture is injected in the sample inlet 12.1 and separated via the separation column 12.2. The separation runs from T ⁇ n g to T end (12.3) until the last substance of interest has left the separation column.
  • FIG. 1 A first figure.
  • FIG. 1 shows the implementation of the method according to the invention as a separation in the second dimension.
  • the black band symbolizes a substance fraction 3 of this substance mixture, which is fixed spatially in the third column segment after a first chromatographic separation.
  • the local fractionation in the 1st dimension has taken place.
  • the vertical dashed line symbolizes the transfer of a substance fraction 3 of the column segment 3 of the first separation column 1 to the separation column of the second dimension shown below.
  • the separation column of the second dimension shown below the separation column 1 of the 1st dimension, has 4 column segments 2.
  • the substance 3 is now, after another local fractionation in the column segment 2 Separation column 1 of the 2nd • Dimension fixed locally.
  • Figure 2 shows the inventive design of PSDu ⁇ lensegmente.
  • a conical seal is guided on a short, fixed at the output of a segment column, capillary in an inner cone at the entrance of another segment column and sealed off both by external mechanical pressure against the fluid pressure of the flowing solvent.
  • a column segment 2 is shown, wherein 5 shows the capillary, which is provided with the conical seal 6.
  • the inner cone 7 is located at the lower end of the column segment 2.
  • the coupling of column segments 2 then takes place, as described above, via the conical seal 6 of one segment with the inner cone 7 of the other segment. This coupling is illustrated in more detail on FIG. 3.
  • FIG. 3 In the lower part of Figure 2 is a plan view of a column segment 2 is shown.
  • FIG. 3 shows the coupling of three column segments 2.
  • An adapter 8 which is provided with a koni ⁇ rule seal 9 for sealing, leads the solvent flow in the coupled segment columns.
  • the three column segments 2 are coupled together by a conical seal 9 and inner cone 7.
  • the conclusion of this arrangement forms a further Adap ⁇ ter 8.1 with an inner cone 7, the z. B. leads into a waste container.
  • the described construction according to the invention of the individual segments and their connection with one another guarantees a minimization of the dead volume between the individual segments. This reduces the broadening of the substance bands during the separation and the loss of substances in the capillaries between the individual segments when decoupled.
  • an automated Vorrich ⁇ device will be explained below.
  • the device can be adapted individually to the most varied requirements of the implementation of the method according to the invention.
  • Representative of the embodiments according to the invention, a few exemplary embodiments are to be treated here in order to clarify the flexibility of the device for use in the method according to the invention.
  • the central element of the automated separating device is a grouping of the segments, which makes it possible to quickly bind and regroup the individual segments. light.
  • several spatial arrangements of the segments and also several mechanical devices are possible.
  • FIG. 4 shows the exemplary arrangement of 5 sections of separation columns 1.
  • the 5 separation columns 1 are each subdivided into 5 column segments.
  • the mobility of the column segments is shown in the upper separation column 1.
  • the circles placed around the column segments symbolize the rotatability of the segments. Shown is the step in the process according to the invention, in which the separation of the substance mixture takes place in the first dimension.
  • the solvent flow for separation in the 1st dimension is represented by the arrow 10. After separation in the first dimension, the column segments of the first separation column 1 are rotated by 90 °.
  • the substances fixed on the first separation column 1 can then be transferred into the second dimension, that is to say the segments of the second separation column 1 which are located below the first separation column 1, by means of the flow stream characterized as arrow 11.
  • FIG. 4 A detail of the arrangement shown in FIG. 4 is shown in more detail in FIG.
  • the rotatable segments 2 are now shown in the direction of distribution in the second dimension.
  • the distribution in the first dimension took place with the flow of the turret shown as arrow 12 through an adapter 8.2, which at the same time serves as a stop for the segments 2 pressed into one another by a pneumatic (optionally also hydraulic or mechanical) element 13.
  • the outlet of the mobile phase flow shown as arrow 14 is located in an adapter 8.3 mounted on the drive rod 15 of the pneumatic element 13.
  • the distribution took place in the 1st dimension can be 5 times in parallel with those shown as arrows 16 Eluent streams follow the distribution in the second dimension.
  • Dashed arrows 69 indicate the mobile phase streams for fractionation in the third dimension.
  • FIG. 6 shows the relationship of the 1st, 2nd and 3rd dimensions for a planar construction of a device according to the invention.
  • the segments are pressed together at different positions, with the following elements: 1st dimension, element 17, 2nd dimension, elements 18 and 3rd dimension, elements 19.
  • the segments are combined in groups on carriages 20 , One group comprises the five segments of the first dimension, four further groups each consist of five segments of the second dimension (shaded in gray). This enables a 5-fold parallel elution, rinsing and conditioning of the segments.
  • a unit for redirecting the solvent streams to the detectors is indicated.
  • the carriages are movable between the 1st and 2nd dimension and the 3rd dimension.
  • the movement of the carriages can be horizontal as well as vertical. Linear technology with drive is used in this exemplary embodiment.
  • the carriages 20 are sprung against each other, so that after release of the pneumatic contact pressure a sufficient distance between the individual carriages is ensured and they can be transported to other positions.
  • Arrow 22 indicates the direction of movement, transporting a carriage with 5 segments from position 1. + 2nd dimension to position 3. Dimension;
  • Arrow 23 indicates the transport direction of a carriage 20 with 5 segments within position 3.
  • Arrow 24 indicates the direction in which the block of pneumatic elements 19 leads to the column segments.
  • 25 is an example of one of the five featured short preparative columns through which parallel elution of the segments occurs at a high flow rate.
  • connection is made by means of adapters via the initially described screw-fastened and quick-seal-free connections.
  • the capillaries 26 leading to fraction collectors are shown.
  • This one-level graphical construction is just one of several embodiments.
  • a further exemplary embodiment is the arrangement of the position 3. Dimension directly above the position 1. + 2. dimension, wherein the transport of the segments 2 takes place in groups of five by portal technology.
  • FIG. 7 illustrates the system of pumps and solvent streams within the device according to the invention for the fractional site fractionation over two dimensions with elution of the substances over short HPLC columns in a third dimension.
  • FIG. 27 identifies five preparative high-pressure gradient pumps. This number allows working in parallel with five different isocrates or gradients in the 2nd and 3rd dimension.
  • a channel of the distribution in the second dimension (arrow 31) and a channel of the elution in the third dimension (arrow 32) are supplied with eluent.
  • the further four high-pressure gradient pumps 27 supply one channel of the distribution in the second dimension (indicated by dashed lines) via electrically or pneumatically controlled 3-position 3-way valves 29 and one channel of the elution in the third dimension with eluent. These channels of elution in the third dimension are represented by the solid lines going to the right from the valves 28 and 29.
  • Arranged under the pumps 27 are the 25 segments 33 for distribution in the 1st and 2nd dimensions.
  • the HPLC columns are labeled for elution in the third dimension. After site fractionation and elution, the five high-pressure gradient pumps 27 are used to rinse and condition all segments and HPLC columns.
  • FIG. 8 shows an exemplary task system, illustrated by the example of fixed-bed injection.
  • 35 represents the 25 segments for distribution in the 1st + 2nd dimension.
  • This is connected to a further motor switching valve 38, which directs the eluent flow to the desired channel of the 1st or 2nd dimension of the distribution.
  • One of the connections shown as a dashed line, leads to the distribution in the first dimension.
  • extracts are distributed over the 1st and 2nd dimension. Parts extracts or extracts of a very limited polarity range can be selectively directed to a segment via the further channels, which are routed from the multiple-motor switching valve 37.
  • the task unit can be coupled out via the changeover valves 39 and a direct connection to the pumps can be made.
  • the connections to the high-pressure gradient pumps are identified by 40.
  • FIG. 1 The complete linking of the feed system and the flow of streams is shown in FIG.
  • the fixed-bed injection is carried out with pump 41.
  • Valve 42 is used to control the multi-selector valves 43 and 44, which release the supply columns 45 successively for elution.
  • the supply of the extracts takes place either via valve 47 in the first dimension or via the valves 48 in the second dimension.
  • the feed columns with pump 49 can be purged without air.
  • the other possible uses of pump 49 are the elution of segments in a channel of the third dimension 50, eben ⁇ if controlled by valve 42.
  • the pumps 51 are used only for distribution in the second dimension and the elution in the third dimension ,
  • the associated valves 53, 54, 55 and 56 to the individual pumps direct the Laufmit- current in the appropriate dimension. Will in the 2.
  • an extract which is intended for distribution can be examined for the polarity and distribution of its constituents by an evaluation with the HPLC on an analytical scale.
  • FIG. 10 shows the structure of an online detection.
  • 57 shows a segment from the distribution in the first dimension, 58 the four segments of the subsequent distribution in the second dimension.
  • the arrow marked 62 shows the flow of the medium through the segment of the 1st dimension in the detector
  • the arrow 63 marks the flow of the medium from the detector further through the segments of the second dimension of the distribution.
  • the detector 60 may include, as required, a UV detector, a refractive index detector, a light scattering detector or any commonly used in HPLC. be a detector.
  • a computer 61 By means of a computer 61, a data recording takes place, the results of which are to be used for the further process of local fractionation and the elution of the segments.
  • an industrial robot is used for automation.
  • the structure of the automated device according to the invention for multi-dimensional spatial fractionation can be simplified and the degree of automation can be increased.
  • FIG. 11 shows the construction scheme of an automated device using a commercial industrial robot.
  • the arm of the industrial robot 64 grips the individual segments and positions them at the intended positions.
  • the distributions in the 1st and 2nd dimension take place on the gray-shaded area.
  • the distributions take place in the third dimension.
  • 65 designates the component which supplies the elec- trode flow to the detectors of the online detection. If this is carried out via a distribution in the 1st dimension, the mobile phase passes through a direct dead volume capillary to the following segments.
  • a separate pneumatically, hydraulically or mechanically acting element for compressing the segments in the case of a distribution in the 1st dimension is dispensed with since both first and second dimension distributions can take place in the first row of the segments.
  • the pneumatic units 66 seal the segments During the distributions in the first and second dimensions, the elements are mutually inclined and the pneumatic units in 67 seal the segments against each other during the distributions in the third dimension.
  • 68 designates the short HPLC columns for elution of the segments in the third dimension, and the lines leaving 68 identify the eluent streams with the eluted substances in the fraction collectors.
  • FIG. 12 shows the principle of the known time fractionation.
  • a mixture is injected in the sample feeder 70 and separated via the separation column 71.
  • the separation 72 runs from Tanfa n g to T end , until the last substance of interest has left the separation column
  • the device according to the invention is combined with an online data processing system for automating the fractionation of location and controlling the elution in a fraction collector.
  • On-line detection in the distribution with on-line data processing ensures effective fractionation of the ingredients of a substance mixture distributed over up to 20 segments.
  • software-controlled data are obtained by peak detection, which are automatically used to fractionate the individual segments from the second dimension.
  • This data is combined with the information obtained from the Distribution for the 1st Dimension distribution, which can be entered into a control software. This is how segments filled with substances become distinguished from empty ones. As a result, only those segments are fractionated in the fraction collector, which can expect substances. All other segments can be rinsed out immediately and conditioned again.
  • the data processing therefore consists of three components:
  • FIGS. 13 and 14 show chromatograms recorded according to the present invention using the method according to the invention and the device according to the invention.
  • FIG. 13 shows a representation of the distribution of a complex extract after local fractionation in the 1st dimension on five segmental columns.
  • Each of the five chromatograms arranged one behind the other shows a partial extract.
  • Each of these five chromatograms is the result of a measurement of the parts extract which has been completely eluted from the respective segment column. In this way, the principle of Ortsfr syndrome ist by means of HPLC can be clearly seen.
  • Different polarity ranges of a complex extract can be fixed by their different migration speeds on different Seg ⁇ pillars.
  • FIG. 14 now shows the representation of the distribution of a partial extract after local fractionation in the 2nd dimension on four segment columns.
  • the last segment from the location fractionation of the 1st dimension (see FIG. 13) with the non-polar connections was used by way of example.
  • Each of these four chromatograms is the result of a measurement of the part extract completely eluted from the respective segment column.
  • FIG. 13 it can clearly be seen how the parts extract was finely divided by the additional dimension of the fractional fractionation and is now ready for a fractionating elution from the respective segment.

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Abstract

L'invention concerne un procédé de séparation de mélanges de produits ainsi qu'un dispositif pour la mise en oeuvre de ce procédé. Le procédé selon l'invention est caractérisé en ce qu'on effectue la séparation sous forme d'un fractionnement local, suivant une technique HPLC. Le dispositif selon l'invention pour la mise en oeuvre de ce procédé est caractérisé en ce qu'il comprend des colonnes de séparation (1) comprenant des segments de colonne (2).
PCT/DE2005/001506 2004-08-25 2005-08-24 Procede et dispositif de separation de melanges de produits WO2006021203A1 (fr)

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DE102004041806.3 2004-08-25
DE200410041806 DE102004041806B4 (de) 2004-08-25 2004-08-25 Verfahren und Vorrichtung zur Auftrennung von Stoffgemischen

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110494746A (zh) * 2017-03-03 2019-11-22 布莱阿姆青年大学 多模态、多检测器液相色谱系统

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GB611080A (en) * 1946-03-04 1948-10-25 Charles Gabriel Lynam Improvements in or relating to chromatographic separation
DE3836343A1 (de) * 1987-11-23 1989-06-01 Werner Hafner Saeulenchromatograph und verfahren zu dessen betrieb
EP0460409A2 (fr) * 1990-05-07 1991-12-11 KRONWALD SEPARATIONSTECHNIK GmbH Brancheur composé pour une colonne de chromatographie
WO2004047948A1 (fr) * 2002-11-26 2004-06-10 Prime Separations, Incorporated Processus et appareil de separation par chromatographie

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US4719011A (en) * 1985-03-22 1988-01-12 H. T. Chemicals, Inc. High pressure liquid chromatography columns

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Publication number Priority date Publication date Assignee Title
GB611080A (en) * 1946-03-04 1948-10-25 Charles Gabriel Lynam Improvements in or relating to chromatographic separation
DE3836343A1 (de) * 1987-11-23 1989-06-01 Werner Hafner Saeulenchromatograph und verfahren zu dessen betrieb
EP0460409A2 (fr) * 1990-05-07 1991-12-11 KRONWALD SEPARATIONSTECHNIK GmbH Brancheur composé pour une colonne de chromatographie
WO2004047948A1 (fr) * 2002-11-26 2004-06-10 Prime Separations, Incorporated Processus et appareil de separation par chromatographie

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110494746A (zh) * 2017-03-03 2019-11-22 布莱阿姆青年大学 多模态、多检测器液相色谱系统
EP3589944A4 (fr) * 2017-03-03 2020-12-30 Brigham Young University Système chromatographique liquide multidétecteur multimodal

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