US3220164A - Recirculation chromatography - Google Patents

Recirculation chromatography Download PDF

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Publication number
US3220164A
US3220164A US210642A US21064262A US3220164A US 3220164 A US3220164 A US 3220164A US 210642 A US210642 A US 210642A US 21064262 A US21064262 A US 21064262A US 3220164 A US3220164 A US 3220164A
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United States
Prior art keywords
column
components
sample
columns
preselected portion
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Expired - Lifetime
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US210642A
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English (en)
Inventor
Marcel J E Golay
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Applied Biosystems Inc
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Perkin Elmer Corp
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Publication date
Application filed by Perkin Elmer Corp filed Critical Perkin Elmer Corp
Priority to US210642A priority Critical patent/US3220164A/en
Priority to DE19631498945 priority patent/DE1498945A1/de
Priority to CH850763A priority patent/CH435801A/de
Priority to GB27749/63A priority patent/GB1027093A/en
Priority to FR7808A priority patent/FR1371275A/fr
Application granted granted Critical
Publication of US3220164A publication Critical patent/US3220164A/en
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
    • G01N30/26Conditioning of the fluid carrier; Flow patterns
    • G01N30/38Flow patterns
    • G01N30/46Flow patterns using more than one column
    • G01N30/468Flow patterns using more than one column involving switching between different column configurations
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
    • G01N30/26Conditioning of the fluid carrier; Flow patterns
    • G01N30/38Flow patterns
    • G01N30/40Flow patterns using back flushing
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
    • G01N30/26Conditioning of the fluid carrier; Flow patterns
    • G01N30/38Flow patterns
    • G01N30/44Flow patterns using recycling of the fraction to be distributed
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
    • G01N30/04Preparation or injection of sample to be analysed
    • G01N30/16Injection
    • G01N30/20Injection using a sampling valve
    • G01N2030/202Injection using a sampling valve rotary valves
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
    • G01N30/26Conditioning of the fluid carrier; Flow patterns
    • G01N30/38Flow patterns
    • G01N2030/382Flow patterns flow switching in a single column
    • G01N2030/385Flow patterns flow switching in a single column by switching valves
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
    • G01N30/26Conditioning of the fluid carrier; Flow patterns
    • G01N30/38Flow patterns
    • G01N30/44Flow patterns using recycling of the fraction to be distributed
    • G01N2030/445Flow patterns using recycling of the fraction to be distributed heart cut

Definitions

  • Chromatography is a well known method for separating a mixture of components into its various constituents.
  • chromatographic techniques are available to those skilled in the art, such as gas-liquid, gas-solid, liquidliquid, and liquid-solid chromatography.
  • gas-liquid technique a column of suitable length is packed with an inert material such as crushed fire brick or kieselguhr. This material is coated with a suitable non-volatile liquid.
  • a carrier gas such as helium or hydrogen is passed through the column.
  • This particular apparatus therefore, comprises a stationary liquid phase and a mobile gas phase.
  • the liquid phase is chosen with a view to the desired separation of a gas or vapor sample to be analyzed.
  • the multicomponent sample is injected into the moving carrier stream which thereupon forces it through the column. As the sample passes through the column, its components are selectively retarded because of their various afiinities for the liquid phase.
  • the eluant from the column is carrier gas containing bands 7 of the various components physically displaced from one another.
  • the primary object of this invention to provide method and apparatus for separating, in columns of relatively short length, those components which would normally require excessively long passage through a partitioning agent.
  • FIG. 1 is a schematic diagram illustrating one arrangement of columns in accordance with this invention
  • FIG. 2 is a schematic diagram of a valving arrangement capable of performing the functions illustrated in FIG. 1;
  • FIG. 3 illustrates another embodiment of the invention
  • FIG. 4 illustrates a still further embodiment of the invention
  • FIG. 5 illustrates still another embodiment of this invention.
  • FIG. 6 illustrates a valving arrangement for achieving the arrangements illustrated in FIG. 5.
  • a chromatographic separation is carried out by a .method which comprises passing a mixture of fluid components sequentially and repeatedly through a plurality of chromatographic separating columns. Simultaneously with such passage, components ahead of a preselected portion of the mixture are removed and components behind the preselected portion are backflushed. The preselected portion is periodically passed into a previously backfiushed column.
  • FIG. 1 discloses a novel sequence of chromatographic column connections proceeding from (a) through (f).
  • the operative sequence for purposes of illustration begins with FIG. 1(a); three columns, 10, 20, 30 are connected by suitable valving arrangements as shown.
  • End 101 of column 10 is connected to a first source of carrier gas P A sample may be injected through S.
  • End 102 of column 10 is directly connected to end 202 of column 20 to allow flow of components directly from column 10 into column 20.
  • a detector 12 is positioned to detect the eluant from column 10.
  • End 201 of column 20 is vented to vent V It will thus be seen that in the embodiment of FIG.
  • column 30 is being flushed by a stream of carrier gas entering end 301 from source P and passing to a vent V
  • a stream of carrier gas entering end 301 from source P and passing to a vent V
  • column 10 is being backflushed by pure carrier gas whereby the heavy-end components retained therein are partially or wholly removed and the column prepared for later use.
  • carrier gas pressure at P may be higher (or lower) than the pressure at P
  • the gas used for this purpose may be completely different if required for the backflushing operation.
  • the valving proceeds to the arrangement shown in FIG. 1(a). This recirculation may proceed for as long a period as necessary to resolve the components of interest.
  • backflushing referred to herein need not be total. It is only necessary that backflushing be continued until the heavier ends remaining in the column will stay ahead of the desired components and, therefore, vent before the next switching operation.
  • FIG. 2 there is illustrated a suitable mechanical arrangement for performing the sequence of operations illustrated in FIG. 1.
  • columns 10, 20, and 30 of FIG. 1 are connected through a twelve port rotary valve 40 having a body portion 41 and a rotor 43.
  • Six of the twelve ports of valve 40 are numbered to correspond with the column end to which each is connected.
  • a prime symbol distinguishes the reference number of the port from that of the column end.
  • the additional ports of valve 40 are lettered or numbered in accordance with the diagram of FIG. 1 insofar as practicable.
  • Four of the remaining'ports in the valve are thus labeled V V P and P
  • the remaining two ports are connected across detector 12 and are thus labeled 121 and 122.
  • a source of carrier gas P supplies both P and P as illustrated.
  • carrier gas may be employed in the reference side of detector 12 if a thermal conductivity bridge detector is employed. It will also be noted that carrier gas from P flows through a valve 42 in its passage to P Valve 42 is representative of a sample injection valve such as that disclosed in US. Patent 2,757,541 which. issued August 7, 1956, to E. S. Watson, et al. A continuous sample supply passes through valve 42 via lines 44, 46. A recorder 48 is illustrated as connected to detector 12.
  • Valve 40 may be operated either manually or automatically. When operated automatically, it may be actuated by detector 12 or by a suitable timer. As illustrated, the rotor 43 of valve 40 includes six passages symmetrically arranged about a diameter of the valve. Pointers 50, 52 indicate the position of the valve rotor and are indexed in accordance with valve position indicating numerals running from 1 through 6. In the position illustrated by FIG. 2, columns 10, 20 and 30 are connected as shown in FIG. 1(a). At the beginning of the cycle, valve 42 is actuated to inject a sampleinto the flowing carrier gas stream passing through conduit 13 from P.
  • FIGS. 3 and 4 each illustrate an assemblage of six columns 62, 64, 66, 72, 74, 76, the ends of each column being numbered by adding the digit 1 or 2 to the reference numeral of the column.
  • Each of these embodiments has the advantage of allowing the injection of two samples simultaneously. In each instance, the sample is injected into column ends 621 and 721.
  • the two samples of each figure are designated S and S
  • sources of carrier gas in each embodiment which are labeled respectively P P P and P P and P represent carrier gas sources used to recirculate the sample components.
  • P and P represent sources of flushing gas which may or may not be similar to the carrier.
  • V V V and V V and V of each figure vent the light ends from the second of the series-connected columns.
  • V and V in each instance are the backflushing vents from the column being prepared for reuse.
  • FIGS. 3(a)-3(e) A comparison of FIGS. 3(a)-3(e) with FIGS. 1(a)-l(e) will indicate that each group of three columns, meaning 62, 64, 66 and 72, 74, 76 is similar to the correspondingly numbered portions of FIG. 1.
  • end 661 is connected to discharge into end 721 of column '72 of the second group.
  • end 761 is connected to discharge into end 621 of column 62.
  • each sample S, and S passes sequentially through all six columns in series.
  • the backfiushing step would be omitted but the light ends would continue to vent as before.
  • FIG. 5 there is illustrated a two column variation of this invention.
  • two pressure sources for carrier gas may be required.
  • One source serves to supply carrier gas for the normal chromatographic separation.
  • the other source serves to flush the previously loaded column by a short high pressure injection of carrier or flushing gas to prevent the fastest desired components from overtaking the slow components during the remainder of the cycles.
  • FIGS. 5(a) through 5(h) These diagrams illustrate a sequence of separation utilizing chromatographic columns 80 and 90. Following the previously described notation, the respective ends of the column are designated by the column reference numeral followed by the digit 1 or 2.
  • FIGS. 5(b), 5(d), 5(1), and 5(h) indicate that, during the flushing period, carrier gas source P is connected to the column containing the components of interest. It should be understood, however, that, during this period, this column may be held in a standby condition without connection either to source P or to vent V
  • FIG. 6 A combination of apparatus suitable for performing the above switching arrangements is shown in FIG. 6.
  • the columns 80, 90 are mounted for rotation.
  • the ends 801, 802, 901, and 902 are directly mounted on valve rotor 110.
  • Rotor 110 is held in rotatable relationship against stator member 112 by means of a suitable compression spring 114.
  • Four ports are contained on the underside of stator 112, in alignment with the equally spaced ends of columns 80 and 90.
  • Valve 116 isconnected into the circuit for performing the short flushing cycle.
  • Valve 116 contains six ports located in a stator disc 117 and is so arranged that adjacent ports may be interconnected by means of rotatable arcuate passages 118, 120, 122 in rotor disc 119.
  • This valve may be similar to the valve disclosed in United States Patent 2,757,541, previously referred to. Valve 116, however, does not contain a sampling loop.
  • P represents a relatively high pressure source of flushing gas leading to port 124. In the illustrated position the flushing gas is vented from port 126 to vent V Meanwhile, carrier gas under normal pressure from P passes into port 128 and from port 130 continues to end 802 of column 80.
  • Sample S may also be inserted into the carrier stream from P From column end 801 the carrier and contained sample pass into port 132 and from port 134 into column end 902. From column end 901, the carrier and separated components may pass to vent V It will be noted that the valve positions illustrated in FIG. 6 define the circuitry of FIG. 5(a). At the proper time, as previously described, valve 116is actuated to interconnect port 132 with 124, 126 with 130, and 128 with 134. It will be seen that, with this combination, the configuration of FIG. 5(1)) is achieved.
  • valve 116 After the lapse of a proper period of time, valve 116 is repositioned to its original state and, at the same time, rotor is rotated in the direction shown by the arrows so that each column end is aligned with the adjacent port of stator 112. This creates the flow condition illustrated in FIG. 5(a).
  • valves 116 and 110 By continuing the relative movements of valves 116 and 110, each of the schematics illustrated by FIGS. 5(a) through 5(b) may be achieved.
  • n the number of plates the greater the separation capability. If each column of a group contains n plates, and if the sample is circulated n times, the effective number of plates becomes n n As a spike-injected component is spread over the order of /n n plates, the number of distinguishable components contained within a column of In plates is of the order of If the user is interested in isolating a single component, n may be made of the order of in.
  • Apparatus for chromatographic separation which comprises:
  • Apparatus for chromatographic separation which comprises:
  • Apparatus for chromatographic separation which comprises:
  • (h) means for repassing said preselected portion through said first column in the same direction as the direction of backflush.
  • Apparatus for chromatographic separation which comprises:
  • a method of chromatographic separation comprising:
  • a method of chromatographic separation comprising:
  • a method of chromatographic separation comprising:
  • a method of chromatographic separation comprising:
  • each period of OTHER REFERENCES backfiushing is short compared to the time of passage of 10 Gas Chromatography by Desty 1958, pages the sample portion through a column. 297499 Academic Press hm 12.
  • the method of claim 9 wherein the plurality is at least three- REUBEN FRIEDMAN, Primary Examiner.

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  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Sustainable Development (AREA)
  • Treatment Of Liquids With Adsorbents In General (AREA)
  • Sampling And Sample Adjustment (AREA)
US210642A 1962-07-18 1962-07-18 Recirculation chromatography Expired - Lifetime US3220164A (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
US210642A US3220164A (en) 1962-07-18 1962-07-18 Recirculation chromatography
DE19631498945 DE1498945A1 (de) 1962-07-18 1963-07-04 Verfahren und Vorrichtung zur chromatographischen Trennung
CH850763A CH435801A (de) 1962-07-18 1963-07-09 Verfahren zur gaschromatographischen Trennung
GB27749/63A GB1027093A (en) 1962-07-18 1963-07-12 Improvements in chromatography
FR7808A FR1371275A (fr) 1962-07-18 1963-07-18 Procédé et dispositif pour la séparation par chromatographie

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Application Number Priority Date Filing Date Title
US210642A US3220164A (en) 1962-07-18 1962-07-18 Recirculation chromatography

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US3220164A true US3220164A (en) 1965-11-30

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CH (1) CH435801A (de)
DE (1) DE1498945A1 (de)
FR (1) FR1371275A (de)
GB (1) GB1027093A (de)

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3332218A (en) * 1964-02-27 1967-07-25 American Air Filter Co Dust collector apparatus
US3477207A (en) * 1966-08-09 1969-11-11 Bp Chem Int Ltd Gas chromatography apparatus and valves suitable for use therein
US3488921A (en) * 1968-01-16 1970-01-13 Aquitaine Petrole Process and apparatus for isotopic enrichment
US3926589A (en) * 1973-12-21 1975-12-16 Toe Jokhannesovich Klementi Device and method for separation of fluid mixture into fractions in a chromatograph
US3992175A (en) * 1974-02-11 1976-11-16 Toe Jokhannesovich Klementi Method of and device for chromatographic separation of fluid mixtures into fractions
US4066536A (en) * 1976-08-09 1978-01-03 Micromeritics Instrument Corporation Particle size separation by suspension flow in an unobstructed passageway
US4276060A (en) * 1979-05-22 1981-06-30 The United States Of America As Represented By The United States Department Of Energy Chromatographic hydrogen isotope separation
EP0092860A1 (de) * 1982-04-28 1983-11-02 Duphar International Research B.V Vorsäule zum Vorkonzentrieren von durch Chromatographie zu trennenden Stoffen, sowie Vorrichtung für ein Flüssigkeitschromatographiesystem und Kupplungsstück für diese Vorrichtung
US5096471A (en) * 1990-09-28 1992-03-17 The Regents Of The University Of Michigan Gas chromatography system and methods
US5141534A (en) * 1990-09-28 1992-08-25 The Regents Of The University Of Michigan Sample collection and inlet systems for gas chromatography apparatus
US5141532A (en) * 1990-09-28 1992-08-25 The Regents Of The University Of Michigan Thermal modulation inlet for gas chromatography system
US5281256A (en) * 1990-09-28 1994-01-25 Regents Of The University Of Michigan Gas chromatography system with column bifurcation and tunable selectivity
US5288310A (en) * 1992-09-30 1994-02-22 The Regents Of The University Of Michigan Adsorbent trap for gas chromatography
US5498279A (en) * 1994-05-13 1996-03-12 Chromatofast High speed gas chromatography system for analysis of polar organic compounds
US20050257600A1 (en) * 2004-02-27 2005-11-24 Arne Karlsson Method and apparatus for expediting analysis of samples
US20140248643A1 (en) * 2013-03-01 2014-09-04 Chromacon Ag Chromatographic process for enrichment and isolation
EP3084420A4 (de) * 2013-12-19 2017-06-28 GE Healthcare Bio-Sciences AB Drehventil
US9700813B2 (en) 2013-05-06 2017-07-11 Tomas Hudlicky Methods and apparatus for time-pulsed chromatography
WO2018011102A1 (en) * 2016-07-13 2018-01-18 Chromacon Ag Purification method and uses thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2841005A (en) * 1956-12-11 1958-07-01 Gulf Oil Corp Chromatographic method and apparatus
GB874742A (en) * 1958-03-04 1961-08-10 Perkin Elmer Corp Improvements relating to vapour fractometer apparatus
US3112639A (en) * 1960-01-04 1963-12-03 Beckman Instruments Inc Dual column gas chromatograph and method for analysis

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2841005A (en) * 1956-12-11 1958-07-01 Gulf Oil Corp Chromatographic method and apparatus
GB874742A (en) * 1958-03-04 1961-08-10 Perkin Elmer Corp Improvements relating to vapour fractometer apparatus
US3112639A (en) * 1960-01-04 1963-12-03 Beckman Instruments Inc Dual column gas chromatograph and method for analysis

Cited By (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3332218A (en) * 1964-02-27 1967-07-25 American Air Filter Co Dust collector apparatus
US3477207A (en) * 1966-08-09 1969-11-11 Bp Chem Int Ltd Gas chromatography apparatus and valves suitable for use therein
US3488921A (en) * 1968-01-16 1970-01-13 Aquitaine Petrole Process and apparatus for isotopic enrichment
US3926589A (en) * 1973-12-21 1975-12-16 Toe Jokhannesovich Klementi Device and method for separation of fluid mixture into fractions in a chromatograph
US3992175A (en) * 1974-02-11 1976-11-16 Toe Jokhannesovich Klementi Method of and device for chromatographic separation of fluid mixtures into fractions
US4066536A (en) * 1976-08-09 1978-01-03 Micromeritics Instrument Corporation Particle size separation by suspension flow in an unobstructed passageway
US4276060A (en) * 1979-05-22 1981-06-30 The United States Of America As Represented By The United States Department Of Energy Chromatographic hydrogen isotope separation
EP0092860A1 (de) * 1982-04-28 1983-11-02 Duphar International Research B.V Vorsäule zum Vorkonzentrieren von durch Chromatographie zu trennenden Stoffen, sowie Vorrichtung für ein Flüssigkeitschromatographiesystem und Kupplungsstück für diese Vorrichtung
US5281256A (en) * 1990-09-28 1994-01-25 Regents Of The University Of Michigan Gas chromatography system with column bifurcation and tunable selectivity
WO1992005850A1 (en) * 1990-09-28 1992-04-16 The Regents Of The University Of Michigan Gas chromatography system and methods
US5141534A (en) * 1990-09-28 1992-08-25 The Regents Of The University Of Michigan Sample collection and inlet systems for gas chromatography apparatus
US5141532A (en) * 1990-09-28 1992-08-25 The Regents Of The University Of Michigan Thermal modulation inlet for gas chromatography system
US5096471A (en) * 1990-09-28 1992-03-17 The Regents Of The University Of Michigan Gas chromatography system and methods
US5288310A (en) * 1992-09-30 1994-02-22 The Regents Of The University Of Michigan Adsorbent trap for gas chromatography
US5498279A (en) * 1994-05-13 1996-03-12 Chromatofast High speed gas chromatography system for analysis of polar organic compounds
US20050257600A1 (en) * 2004-02-27 2005-11-24 Arne Karlsson Method and apparatus for expediting analysis of samples
US6968729B1 (en) * 2004-02-27 2005-11-29 Uop Llc Method and apparatus for expediting analysis of samples
US20140248643A1 (en) * 2013-03-01 2014-09-04 Chromacon Ag Chromatographic process for enrichment and isolation
US9073970B2 (en) * 2013-03-01 2015-07-07 Chromacon Ag Chromatographic process for enrichment and isolation
US9700813B2 (en) 2013-05-06 2017-07-11 Tomas Hudlicky Methods and apparatus for time-pulsed chromatography
EP3084420A4 (de) * 2013-12-19 2017-06-28 GE Healthcare Bio-Sciences AB Drehventil
US10309938B2 (en) 2013-12-19 2019-06-04 Ge Healthcare Bio-Sciences Ab Rotary valve
WO2018011102A1 (en) * 2016-07-13 2018-01-18 Chromacon Ag Purification method and uses thereof
CN109475789A (zh) * 2016-07-13 2019-03-15 克罗麦肯公司 纯化方法及其用途
CN109475789B (zh) * 2016-07-13 2020-06-05 克罗麦肯公司 纯化方法及其用途
US11180526B2 (en) 2016-07-13 2021-11-23 Chromacon Ag Purification method and uses thereof

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CH435801A (de) 1967-05-15
GB1027093A (en) 1966-04-20
FR1371275A (fr) 1964-09-04
DE1498945A1 (de) 1969-07-03

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