US3373872A - Apparatus for carrying out a rapid chromatography of amino acid and similar mixtures - Google Patents

Apparatus for carrying out a rapid chromatography of amino acid and similar mixtures Download PDF

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US3373872A
US3373872A US444247A US44424765A US3373872A US 3373872 A US3373872 A US 3373872A US 444247 A US444247 A US 444247A US 44424765 A US44424765 A US 44424765A US 3373872 A US3373872 A US 3373872A
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valve
reservoirs
way
column
outlet
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Hrdina Jiri
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Czech Academy of Sciences CAS
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    • 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
    • G01N30/468—Flow patterns using more than one column involving switching between different column configurations
    • 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
    • G01N30/04—Preparation or injection of sample to be analysed
    • G01N30/24—Automatic injection systems
    • 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
    • G01N30/28—Control of physical parameters of the fluid carrier
    • G01N30/34—Control of physical parameters of the fluid carrier of fluid composition, e.g. gradient
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers

Definitions

  • the present invention relates to an apparatus for ac complishing a rapid chromatography of complex mixtures such as amino acid mixtures.
  • an apparatus for carrying out the separation of complex mixtures having one or more chromatography columns wherein when the apparatus comprises at least two columns, the inlet of each column is connected through at least one two-way valve to a single pump, the intake side of which is connected to a multiple-way valve, at least three inlets of which are respectively connected directly to supply conduits from at least two elution buffer solution containers and to a supply conduit from a regenerating solution container and at least two sample reservoirs connected either to the intake side of the pump or between the pump and the columns, and wherein when the apparatus comprises a single column, the inlet of said column is connected directly to the pump.
  • the sample reservoirs may be arranged between the columns and the two-way valve or, alternatively, between the pump and a two-Way valve.
  • a multiple-way automatic valve Preferably incorporated is a multiple-way automatic valve, the individual branches or ports of which are connected to the sample reservoirs, while its center is connected to the two-way valve which in turn is connected to the column.
  • the sample reservoirs may be connected to an automatic multiple-way valve having an outlet connected to an input of said multiple-way valve.
  • An advantage of the apparatus according to the present invention consists in the fact that a minimum of mechani cal means is required, whether the work is performed on a single column or on two or more columns. Moreover, it is possible to use even simple pumps for subordinate or mechanical means.
  • the apparatus can be used to advantage primarily with an automatic charging of samples from the reservoirs holding previously prepared samples, this being an important feature in practice in order that the times for performance of complete analyses may be shortened.
  • the apparatus can however, be used to advantage even for a manual dosage to the columns, the entire apparatus being thereby simplified to a point where it can be put together from the above standard parts.
  • FIG. 1 features schematically an apparatus intended for a pair of columns
  • FIG. 2 illustrates schematically the type of connection when pressure reservoirs or dosers are used
  • FIG. 3 illustrates an apparatus with a pair of two-way automatic valves
  • FIG. 4 shows one alternative of construction of pressure reservoirs or dosers
  • FIGS. 5 and 6 illustrate two alternative ways in which one multiple-way valve is used instead of two;
  • FIG. 7 illustrates the connections in the case when a single column is used.
  • the apparatus shown in FIG. 1 consists of two chromatography columns 1 and 2 which are connected through their bottom capillary outlets to a four-way distributor valve 3.
  • This distributor valve can connect the outlet of the respective column either to an evaluating device (not shown) by way of a duct 4 or to an outlet by way of a duct 5.
  • the capillary inlets to the columns 1 and 2 are connected by way of a two-way valve 6 to the outlet branch of a single pump 7, the intake branch of which is connected to a multi-way valve 8.
  • the valve 8 has six equally spaced inlet branches and a central outlet branch which is connected to the pump 7 as shown.
  • One of the inlet branches to the valve 8 is connected to the outlet branch of an automatic multi-way valve 10, the inlet branches of which are connected with a plurality of sample reservoirs 9.
  • the inlet branches of the valve 8 located on each side of the inlet branch connected to the valve 10 are joined together by a common connection which is connected to a container 11 holding an elution buffer of a particular pH value.
  • Two other reservoirs 12, 13 hold elution buflFers of different pH values and are connected to respective inlets of the valve 8.
  • the sixth inlet of the valve 8 is connected to a container 14 holding a regenerating solution.
  • the complete separation of a sample may be achieved in one revolution of the valve, i.e., starting from the top inlet of the valve 8, first the elution buffer from container 11 is drawn through the pump 7 and pumped into either of the columns 1 or 2 depending on how the valve 6 is arranged, then a sample from one of the reservoirs 9 is pumped into the particular column, then the elution buffer from container 11 again which is followed successively by elution bulfers from containers 12, 13 and finally at the completion of the separation the regenerating solution from container 14 is pumped through the respective column.
  • the sample reservoirs 9 are unpressurized i.e. arranged on the input side of the pump 7 and thereby the samples in the reservoirs are under ambient pressure. It is an essential feature of this embodiment of the invention that all the passages, including those of valves 6, 8 and 10, the pump 7 and the distributor valve 3, through which a sam ple from any one of the reservoirs 9 flows, are of a capillary type and have a minimum of dead spaces thereby ensuring the maximum amount of the particular sample may be delivered to the respective column.
  • FIG. 2 to be considered in view of FIG. 1 shows schematically an arrangement for use when pressure sample reservoirs or dosers 15 are used, these dosers being symbolized in the drawing by squares outlined in broken lines.
  • Dosers are reservoirs which have their inlets connected to a source of above ambient pressure which in the present embodiment is the pressure side of the pump 7.
  • the arrangement of the apparatus is such that the pressure reservoirs or dosers 15 are connected between the respective chromatography columns 1, 2 and the outlet branches of the two-way valve 6, the connection between the respective reservoirs or dosers 15 and the columns 1, 2 being of capillary type.
  • the inlet branch of the valve 6 is connected by way of the pump 7 to the center outlet branch of the multi-way valve 8 which may be an automatic six-way valve.
  • This embodiment enables the possibility for a step-type gradient elution to be carried out as will be described in the following.
  • elution buffers with standard pH values of 3.24, 4.25 and 5.28 are used, their containers are connected to inlet branches 16, 17 and 18 of the valve 8, the regenerating solution container 14 is connected to inlet branch 19 which leaves two further inlet branches for connection to reservoirs containing a finer, step-type gradient elution.
  • valve 8 can have four Ways only, or, alternatively it may be substituted by two automatic two-way valves 20 as shown in FIG. 3.
  • FIG. 4 shows one of the possible arrangements of the pressure reservoir 15 connected for instance, to a six-way capillary automatic valve 10, a central outlet of which leads to a capillary two-way automatic valve 6 which enables an application of a multiple-way valve 10 to both columns 1 and 2 alternately; this arrangement differs from the embodiment illustrated in FIG. 2, where the two-way valve 6 is connected to the input side of pressure reservoirs or dosers 15 each column having its own pressure reservoir.
  • An advantage of the embodiment illustrated in FIG. 4 consists in a shorter and less complex capillary connection with any one of the closers 15 to the respective columns 1 and 2.
  • This valve 8 has to be a multiple-way valve so as to permit a successive interconnection of the central outlet to the intake branches for supply from the respective buffer containers and from sample storage reservoirs 9.
  • the valve 8 is a multiple-way valve having for example six inlet branches.
  • the first, third and fifth of the inlet branches, counting in a clockwise direction are joined together by a commonly connecting supply branch 21 for individual elution buffers and a regenerating solution is connected to said common connection.
  • Said supply branch 21 may be connected to the outlet of a multiple-way valve (not shown) to the inlets of which are connected to the respective containers of said elution buffers and said regenerating solution.
  • the second, fourth and sixth of the said inlet branches of the valve 8 are separately connected tosample reservoirs 9.
  • the central outlet from the valve 8 may be connected either to the intake branch of a pump 7 in case the sample reservoirs 9 are of pressureless type or to a chromatography column or columns in case the sample reservoirs 9 are of pressure type.
  • a basic buffer is supplied to the column by way of the supply branch 21, then the valve is turned so that the outlet is connected to the second inlet through which a sample is conveyed to the column, the valve is then turned so that the outlet is connected to the third inlet through which one or more elution buffers are supplied to the column by way of supply branch 21 until the separation of the sample is complete after which a regenerating solution followed by the basic buffer is fed into the column by way of supply branch 21, the cycle is then repeated by turning the valve 8 to the fourth inlet to admit the next sample to the column.
  • the embodiment shown in FIG. 6 is a modification of that shown in FIG. 5.
  • the main difference between the two embodiments is that instead of the common supply branch 21 in FIG. 5 the valve 8 in FIG. 6 is a bigger valve than that in FIG. 5 and has many more inlet branches e.g., ten shown in FIG. 6.
  • the first, third, sixth and eighth of the inlet branches are joined together by a common connection which may for example, be connected to a first elution buffer container; the fourth and ninth of the said inlet branches are joined together by a common connection which may for example, be connected to a second elution buffer container; the fifth and tenth of the said inlet branches are joined together by a common connection which may for example, be connected to a regenerating solution container, and the second and seventh of the said inlet branches are separately connected to respective sample reservoirs 9.
  • the central outlet branch of the valve 8 may be connected in either of the ways described with respect to FIG. 5. By successive connection of the inlets of the valve 8 to the outlet for appropriate periods of time, complete separations of samples can be carried out in turn by rotating the valve 8 in a clockwise direction (FIG. 6).
  • FIG. 7 a single chromatography column 1, having a capillary outlet 4, is connected by way of pump 7 to the outlet branch of'a multiple-way valve 8.
  • One inlet branch of the valve 8 is connected to an outlet branch of an automatic multiple-way valve 10 having sample reservoirs 9 connected separately to the inlet branches thereof.
  • the inlet branches of the valve 8 arranged on each side of the inlet branch connected to the valve 10 are joined together by a common connection which is connected to a container 11 of a basic elution buffer.
  • the remaining inlet branches may, for example, be connected to containers holding other elution buffers and a regenerating solution.
  • the connections between the valve 10 and the column are all of capillary type.
  • an apparatus for the chromatography of amino acids and similar mixtures comprising in combination a plurality of reservoirs for the samples to be analyzed; a first hydraulic multi-way valve distributor having a plurality of intakes each associated with one of said reservoirs and a common first outlet; a plurality of containers for the eluent; a second multi-way valve distributor having a plurality of intakes each associated with one of said containers and a common second outlet leading into said first distributor; not more than two columns arranged in parallel; pumping means drawing liquid from said first outlet and delivering it selectively to one of said columns; third valve means effecting such selective delivery; an outlet line leading from each column; and fourth valve means selectively connecting said outlet lines to an evaluating device.
  • An apparatus for the chromatography of amino acids and similar mixtures according to claim 1 comprising a pressure doser in front of each column.
  • An apparatus for the chromatography of amino acids and similar mixtures according to claim 1 comprising a pressure dosing device between the pumping means and the third valve means.

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Description

March 19, 1968 .1. HRDINA' 3,373,872
APPARATUS FOR CARRYING OUT A RAPID CHROMATOGRAPHY OF AMINO ACID AND SIMILAR MIXTURES Filed March 51, 1965 5 Sheets-Sheet 1 March 19, 1968 J. HRDINA 3,373,872
APPARATUS FOR CARRYING OUT A RAPID CHROMATOGRAPHY OF AMINO ACID AND SIMILAR MIXTURES Filed March 31, 1965 s Sheets-Sheet FIG. 3
3,373,872 APPARATUS FOR CARRYING OUT A RAPID CHROMATOGRAPHY OF AMINO J. HRDINA ACID AND SIMILAR MIXTURES 5 Sheets-Sheet 5 8 w 6 w 9 1 1 5 9 h 1 m a .h M m d a m 1 INVENTOR.
United States Patent ABSTRACT OF THE DISCLOSURE A chromatographic apparatus particularly for amino acids and similar mixtures in which a pump feeds eluents from their containers and samples to be analyzed from their respective containers into one or two columns.
The present invention relates to an apparatus for ac complishing a rapid chromatography of complex mixtures such as amino acid mixtures.
Heretofore known semi-automatic and automatic apparatus for the analysis of amino acid and similar complex mixtures use two or three columns which are connected, as a rule, to two or more pumps in order to ob tain a throughflow of elution buffers and of a reagent solution through the column in addition to a pump for a ninhydrin reagent. An apparatus has already been constructed which, in the case of a single column and for practising gradient elution, uses only one pump in addition to that used for ninhydrin. This apparatus requires a rather intricate mixing chamber for varying the quality of the buffer and a special safety device for accurately terminating the period during which liquid is drawn from the mixer in order to prevent any possible intrusion of air into the pump of the column.
The disadvantages of these types of apparatus are obviated by the present invention.
According to the invention there is provided an apparatus for carrying out the separation of complex mixtures having one or more chromatography columns, wherein when the apparatus comprises at least two columns, the inlet of each column is connected through at least one two-way valve to a single pump, the intake side of which is connected to a multiple-way valve, at least three inlets of which are respectively connected directly to supply conduits from at least two elution buffer solution containers and to a supply conduit from a regenerating solution container and at least two sample reservoirs connected either to the intake side of the pump or between the pump and the columns, and wherein when the apparatus comprises a single column, the inlet of said column is connected directly to the pump.
The sample reservoirs may be arranged between the columns and the two-way valve or, alternatively, between the pump and a two-Way valve. Preferably incorporated is a multiple-way automatic valve, the individual branches or ports of which are connected to the sample reservoirs, while its center is connected to the two-way valve which in turn is connected to the column. Further, the sample reservoirs may be connected to an automatic multiple-way valve having an outlet connected to an input of said multiple-way valve.
An advantage of the apparatus according to the present invention consists in the fact that a minimum of mechani cal means is required, whether the work is performed on a single column or on two or more columns. Moreover, it is possible to use even simple pumps for subordinate or mechanical means. The apparatus can be used to advantage primarily with an automatic charging of samples from the reservoirs holding previously prepared samples, this being an important feature in practice in order that the times for performance of complete analyses may be shortened. The apparatus can however, be used to advantage even for a manual dosage to the columns, the entire apparatus being thereby simplified to a point where it can be put together from the above standard parts.
Embodiments of the present invention will now be described, by way of example, with refernce to the accompanying drawings, wherein:
FIG. 1 features schematically an apparatus intended for a pair of columns;
FIG. 2 illustrates schematically the type of connection when pressure reservoirs or dosers are used;
FIG. 3 illustrates an apparatus with a pair of two-way automatic valves;
FIG. 4 shows one alternative of construction of pressure reservoirs or dosers;
FIGS. 5 and 6 illustrate two alternative ways in which one multiple-way valve is used instead of two;
FIG. 7 illustrates the connections in the case when a single column is used.
The apparatus shown in FIG. 1 consists of two chromatography columns 1 and 2 which are connected through their bottom capillary outlets to a four-way distributor valve 3. This distributor valve can connect the outlet of the respective column either to an evaluating device (not shown) by way of a duct 4 or to an outlet by way of a duct 5. The capillary inlets to the columns 1 and 2 are connected by way of a two-way valve 6 to the outlet branch of a single pump 7, the intake branch of which is connected to a multi-way valve 8. The valve 8 has six equally spaced inlet branches and a central outlet branch which is connected to the pump 7 as shown. One of the inlet branches to the valve 8 is connected to the outlet branch of an automatic multi-way valve 10, the inlet branches of which are connected with a plurality of sample reservoirs 9. The inlet branches of the valve 8 located on each side of the inlet branch connected to the valve 10 are joined together by a common connection which is connected to a container 11 holding an elution buffer of a particular pH value. Two other reservoirs 12, 13 hold elution buflFers of different pH values and are connected to respective inlets of the valve 8. The sixth inlet of the valve 8 is connected to a container 14 holding a regenerating solution. By rotating the valve 8 in a clockwise direction the complete separation of a sample may be achieved in one revolution of the valve, i.e., starting from the top inlet of the valve 8, first the elution buffer from container 11 is drawn through the pump 7 and pumped into either of the columns 1 or 2 depending on how the valve 6 is arranged, then a sample from one of the reservoirs 9 is pumped into the particular column, then the elution buffer from container 11 again which is followed successively by elution bulfers from containers 12, 13 and finally at the completion of the separation the regenerating solution from container 14 is pumped through the respective column.
The sample reservoirs 9 are unpressurized i.e. arranged on the input side of the pump 7 and thereby the samples in the reservoirs are under ambient pressure. It is an essential feature of this embodiment of the invention that all the passages, including those of valves 6, 8 and 10, the pump 7 and the distributor valve 3, through which a sam ple from any one of the reservoirs 9 flows, are of a capillary type and have a minimum of dead spaces thereby ensuring the maximum amount of the particular sample may be delivered to the respective column.
FIG. 2 to be considered in view of FIG. 1 shows schematically an arrangement for use when pressure sample reservoirs or dosers 15 are used, these dosers being symbolized in the drawing by squares outlined in broken lines. Dosers are reservoirs which have their inlets connected to a source of above ambient pressure which in the present embodiment is the pressure side of the pump 7. The arrangement of the apparatus is such that the pressure reservoirs or dosers 15 are connected between the respective chromatography columns 1, 2 and the outlet branches of the two-way valve 6, the connection between the respective reservoirs or dosers 15 and the columns 1, 2 being of capillary type. The inlet branch of the valve 6 is connected by way of the pump 7 to the center outlet branch of the multi-way valve 8 which may be an automatic six-way valve. This embodiment enables the possibility for a step-type gradient elution to be carried out as will be described in the following. When only three elution buffers, with standard pH values of 3.24, 4.25 and 5.28 are used, their containers are connected to inlet branches 16, 17 and 18 of the valve 8, the regenerating solution container 14 is connected to inlet branch 19 which leaves two further inlet branches for connection to reservoirs containing a finer, step-type gradient elution.
If it is desired to only use three elution buffer containers and one regenerating solution container the valve 8 can have four Ways only, or, alternatively it may be substituted by two automatic two-way valves 20 as shown in FIG. 3.
FIG. 4 shows one of the possible arrangements of the pressure reservoir 15 connected for instance, to a six-way capillary automatic valve 10, a central outlet of which leads to a capillary two-way automatic valve 6 which enables an application of a multiple-way valve 10 to both columns 1 and 2 alternately; this arrangement differs from the embodiment illustrated in FIG. 2, where the two-way valve 6 is connected to the input side of pressure reservoirs or dosers 15 each column having its own pressure reservoir. An advantage of the embodiment illustrated in FIG. 4 consists in a shorter and less complex capillary connection with any one of the closers 15 to the respective columns 1 and 2. Instead of two automatic multiple-way valves arranged one after another it is pos sible according to FIG. 4 to use only one multiple-way valve 8 as shown in FIGS. and 6. This valve 8 has to be a multiple-way valve so as to permit a successive interconnection of the central outlet to the intake branches for supply from the respective buffer containers and from sample storage reservoirs 9.
In the embodiment shown in FIG. 5 the valve 8 is a multiple-way valve having for example six inlet branches. The first, third and fifth of the inlet branches, counting in a clockwise direction are joined together by a commonly connecting supply branch 21 for individual elution buffers and a regenerating solution is connected to said common connection. Said supply branch 21 may be connected to the outlet of a multiple-way valve (not shown) to the inlets of which are connected to the respective containers of said elution buffers and said regenerating solution. The second, fourth and sixth of the said inlet branches of the valve 8 are separately connected tosample reservoirs 9. The central outlet from the valve 8 may be connected either to the intake branch of a pump 7 in case the sample reservoirs 9 are of pressureless type or to a chromatography column or columns in case the sample reservoirs 9 are of pressure type. By connecting the outlet of the valve 8 to the supply branch inlets and to the respective sample inlets for appropriate periods of time, complete separations of the respective samples can be carried out in turn by rotating the valve 8 in a clockwise direction (FIG. 5). For example, starting with the outlet branch connected to the first inlet, a basic buffer is supplied to the column by way of the supply branch 21, then the valve is turned so that the outlet is connected to the second inlet through which a sample is conveyed to the column, the valve is then turned so that the outlet is connected to the third inlet through which one or more elution buffers are supplied to the column by way of supply branch 21 until the separation of the sample is complete after which a regenerating solution followed by the basic buffer is fed into the column by way of supply branch 21, the cycle is then repeated by turning the valve 8 to the fourth inlet to admit the next sample to the column.
The embodiment shown in FIG. 6 is a modification of that shown in FIG. 5. The main difference between the two embodiments is that instead of the common supply branch 21 in FIG. 5 the valve 8 in FIG. 6 is a bigger valve than that in FIG. 5 and has many more inlet branches e.g., ten shown in FIG. 6. Counting in a clockwise direction, the first, third, sixth and eighth of the inlet branches are joined together by a common connection which may for example, be connected to a first elution buffer container; the fourth and ninth of the said inlet branches are joined together by a common connection which may for example, be connected to a second elution buffer container; the fifth and tenth of the said inlet branches are joined together by a common connection which may for example, be connected to a regenerating solution container, and the second and seventh of the said inlet branches are separately connected to respective sample reservoirs 9. The central outlet branch of the valve 8 may be connected in either of the ways described with respect to FIG. 5. By successive connection of the inlets of the valve 8 to the outlet for appropriate periods of time, complete separations of samples can be carried out in turn by rotating the valve 8 in a clockwise direction (FIG. 6).
The entire connection however, is considerably simplified by the embodiment illustrated in FIG. 7. In this figure a single chromatography column 1, having a capillary outlet 4, is connected by way of pump 7 to the outlet branch of'a multiple-way valve 8. One inlet branch of the valve 8 is connected to an outlet branch of an automatic multiple-way valve 10 having sample reservoirs 9 connected separately to the inlet branches thereof. The inlet branches of the valve 8 arranged on each side of the inlet branch connected to the valve 10 are joined together by a common connection which is connected to a container 11 of a basic elution buffer. The remaining inlet branches may, for example, be connected to containers holding other elution buffers and a regenerating solution. The connections between the valve 10 and the column are all of capillary type.
While specific embodiments of my invention have been shown and described in detail to illustrate the application of the principles of my invention, it will be understood that the same may be otherwise embodied without departing from such principles.
What I claim as my invention is:
1. In an apparatus for the chromatography of amino acids and similar mixtures the improvement comprising in combination a plurality of reservoirs for the samples to be analyzed; a first hydraulic multi-way valve distributor having a plurality of intakes each associated with one of said reservoirs and a common first outlet; a plurality of containers for the eluent; a second multi-way valve distributor having a plurality of intakes each associated with one of said containers and a common second outlet leading into said first distributor; not more than two columns arranged in parallel; pumping means drawing liquid from said first outlet and delivering it selectively to one of said columns; third valve means effecting such selective delivery; an outlet line leading from each column; and fourth valve means selectively connecting said outlet lines to an evaluating device.
2. An apparatus for the chromatography of amino acids and similar mixtures according to claim 1 comprising a pressure doser in front of each column.
3. An apparatus for the chromatography of amino acids and similar mixtures according to claim 1 comprising a pressure dosing device between the pumping means and the third valve means.
(References on following page) 5 6 References Cited OTHER REFERENCES UNITED STATES PATENTS Separation of Bases and Amino Acids by Displacement Chromatography on Ion-Exchange Columns, S. M. 13
5g Partridge, Faraday Soc. Disc., No. 7, 1949, pp. 296-305 ova 5 2 011 1 1959 coggeshall 55 197 X REUBEN FRIEDMAN, Primary Examiner.
3,097,163 7/ 1963 Riddick 210- J, DE CESARE, Assistant Examiner.
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Cited By (42)

* Cited by examiner, † Cited by third party
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US3446057A (en) * 1966-10-14 1969-05-27 Varian Associates Method and apparatus for chromatography
US3504799A (en) * 1968-04-02 1970-04-07 Beckman Instruments Inc Sample injector
US3508880A (en) * 1966-01-07 1970-04-28 Ceskoslovenska Akademie Ved Apparatus for carrying out chromatographic analyses of amino acids,their mixtures and similar materials
US3514210A (en) * 1968-01-15 1970-05-26 Jiri Hrdina Device for programmed drawing off of gas bubbles from a measuring cell separator and the liquid from the extinction cell space
US3518874A (en) * 1964-05-26 1970-07-07 Ceskoslovenska Akademie Ved Apparatus for analyzing mixtures of substances in one or a plurality of chromatographic columns
US3531258A (en) * 1967-11-16 1970-09-29 Us Health Education & Welfare Apparatus for the automated synthesis of peptides
US3533933A (en) * 1967-03-31 1970-10-13 Hannig Kurt Process and device for the isolation of fractions of a substance mixture electrophoretically separated in a carrier gel
US3575295A (en) * 1968-04-11 1971-04-20 Hitachi Ltd Sample introducing system for use in liquid chromatography
US3847507A (en) * 1972-05-17 1974-11-12 Toyo Soda Mfg Co Ltd Liquid supply system by pump
US3926809A (en) * 1973-10-10 1975-12-16 Roosevelt J Jones Multi-column fractionator
US3981801A (en) * 1973-02-14 1976-09-21 University Of Edinburgh Gradient storage method for liquid chromatography
US4003243A (en) * 1974-07-18 1977-01-18 Societe Nationale Des Petroles D'aquitaine Method of analysis by liquid-phase chromatography
US4112743A (en) * 1976-09-15 1978-09-12 Phillips Petroleum Company Step-wise gradient carrier for liquid chromatography
US4116046A (en) * 1977-08-05 1978-09-26 Hoffmann-La Roche Inc. Liquid chromatography system
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US4116046A (en) * 1977-08-05 1978-09-26 Hoffmann-La Roche Inc. Liquid chromatography system
US4219530A (en) * 1978-01-27 1980-08-26 Brinkmann Instruments, Inc. Apparatus for analyzing biological specimens
US4158630A (en) * 1978-02-24 1979-06-19 Stearns Stanley D Chromatographic multi-sample valving apparatus
DE2926521A1 (en) * 1978-07-07 1980-01-17 Technicon Instr METHOD AND DEVICE FOR INCREASING THE THROUGHPUT OF A CHROMATOGRAPHY SYSTEM
US4204952A (en) * 1978-07-07 1980-05-27 Technicon Instruments Corporation Chromatographic apparatus and method
US4364263A (en) * 1980-09-15 1982-12-21 Burroughs Wellcome Co. High pressure liquid chromatographic system
US4470832A (en) * 1982-03-10 1984-09-11 Hitachi, Ltd. Gas chromatographic apparatus
US5122275A (en) * 1986-05-08 1992-06-16 A. E. Staley Manufacturing Company Simulated moving bed chromatographic separation
US4872992A (en) * 1987-12-09 1989-10-10 Atlantic Richfield Company Method and apparatus for analyzing diluted and undiluted fluid samples
US4950397A (en) * 1987-12-09 1990-08-21 Atlantic Richfield Company Apparatus for analyzing diluted and undiluted fluid samples
US5064539A (en) * 1988-05-17 1991-11-12 Ryoka Techno Engineering & Construction Co. Method of chromatographic separation
DE3907930C1 (en) * 1989-03-11 1990-06-13 Hans-Peter Dr. 6464 Linsengericht De Kabus
US5089126A (en) * 1989-03-31 1992-02-18 Lehigh University Method and apparatus for capillary hydrodynamic fractionation
US5512168A (en) * 1990-03-05 1996-04-30 Applied Separations, Inc. Programmable solid phase extraction and elution device
US5443734A (en) * 1990-03-05 1995-08-22 Applied Separations, Inc. Programmable solid phase extraction and elution device
US5071547A (en) * 1990-03-23 1991-12-10 Separations Technology, Inc. Column chromatographic column apparatus with switching capability
US6415670B1 (en) * 1999-03-26 2002-07-09 Yamazen Corporation Injection apparatus
WO2000064557A1 (en) * 1999-04-23 2000-11-02 Advanced Bioanalytical Services, Inc. High-throughput parallel liquid chromatography system
US6318157B1 (en) 1999-04-23 2001-11-20 Advanced Bioanalytical Services, Inc. High-throughput parallel liquid chromatography system
US6581442B1 (en) * 1999-05-19 2003-06-24 Eisai Co., Ltd. Splitted tubing apparatus for gradient high performance liquid chromatography
US6551387B2 (en) * 2000-07-26 2003-04-22 Organo Corporation Gas separation apparatus
US7281408B2 (en) 2000-08-02 2007-10-16 Symyx Technologies, Inc. Parallel gas chromatograph with microdetector array
US6701774B2 (en) 2000-08-02 2004-03-09 Symyx Technologies, Inc. Parallel gas chromatograph with microdetector array
US20040139784A1 (en) * 2000-08-02 2004-07-22 Symyx Technologies, Inc. Parallel gas chromatograph with microdetector array
US20090324447A1 (en) * 2000-12-28 2009-12-31 John Brann Multi column chromatography system
US7790026B2 (en) 2000-12-28 2010-09-07 Cohesive Technologies Inc. Multi column chromatography system
US20050016263A1 (en) * 2001-06-07 2005-01-27 Yoshio Yamauchi Liquid chromatograph and analysis system
US7066011B2 (en) * 2001-06-07 2006-06-27 Nano Solution, Inc. Liquid chromatograph and analysis system
US20040251203A1 (en) * 2003-06-16 2004-12-16 Yury Zelechonok Method and apparatus for high pressure liquid chromatography
US6893569B2 (en) * 2003-06-16 2005-05-17 Sielc Technologies Method and apparatus for high pressure liquid chromatography
US20100083739A1 (en) * 2003-11-05 2010-04-08 Agilent Technologies, Inc. Chromatography System with Fluid Intake Management
US7600415B2 (en) * 2003-11-05 2009-10-13 Agilent Technologies, Inc. Chromatography system with waste output
US20070000313A1 (en) * 2003-11-05 2007-01-04 Agilent Technologies, Inc. Chromatography system with waste output
US7992429B2 (en) 2003-11-05 2011-08-09 Agilent Technologies, Inc. Chromatography system with fluid intake management
US8438911B2 (en) 2003-11-05 2013-05-14 Agilent Technologies, Inc. Chromatography system with fluid intake management
US20090039024A1 (en) * 2005-06-21 2009-02-12 Waters Investments Limited Apparatus and methods for performing steps of a multi-step process in parallel
US8802035B2 (en) 2005-06-21 2014-08-12 Waters Technologies Corporation Apparatus and methods for performing steps of a multi-step process in parallel
WO2014134063A1 (en) * 2013-02-26 2014-09-04 The Translational Genomics Research Institute Liquid degassing for nano-flow chromatography
US20160139093A1 (en) * 2013-06-14 2016-05-19 Agilent Technologies, Inc. Hplc sample introduction with coupling sample reservoirs in parallel between mobile phase drive and separation unit
US9823226B2 (en) * 2013-06-14 2017-11-21 Agilent Technologies, Inc. HPLC sample introduction with coupling sample reservoirs in parallel between mobile phase drive and separation unit
US20160327514A1 (en) * 2015-05-08 2016-11-10 Agilent Technologies, Inc. Correcting sample metering inaccuracy due to thermally induced volume change in sample separation apparatus
US11307181B1 (en) 2018-07-14 2022-04-19 Sielc Technologies Corporation HPLC system with mixed-mode columns for measuring charged analytes in complex mixtures
US11467137B2 (en) * 2020-01-22 2022-10-11 Shimadzu Corporation Liquid chromatograph and analysis execution method

Also Published As

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SE305555B (en) 1968-10-28
JPS5247357B1 (en) 1977-12-01
DE1598205B1 (en) 1971-05-19
GB1106093A (en) 1968-03-13

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