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METHOD AND APPARATUS FOR GENERATING A HIGH PURITY CHROMATOGRAPHY ELUENT
BACKGROUND OF THE INVENTION 5
The present invention relates to a method and apparatus for the generation of a high purity chromatography eluent, particularly a gradient eluent.
In practicing liquid chromatography, a sample containing multiple components is directed through a chromatography medium contained typically in an ion exchange resin bed. The components are separated on elution from the bed in a solution of eluent.
One effective form of liquid chromatography is referred to as ion chromatography. In this known technique, the ions in the sample solution are directed through a chromatographic separation stage using such eluent containing an electrolyte and thereafter to a suppression stage, followed by detection, typically by an 20 electrical conductivity detector. In the suppression stage, the electrical conductivity of the electrolyte is suppressed but not that of the separated ions so that the latter may be detected by a conductivity cell. This technique is described in detail in U.S. Pat. Nos. 3,897,213, 3,920,397, 3,925,019 and 3,956,559.
Suppression or stripping of the electrolyte by an ion exchange resin bed is described in the prior art references. A different form of suppressor is described in EPA Pub. No. 32,770 published July 29, 1981. Here, an 3Q ion exchange membrane in the form of a Fiber or sheet is used in place of the resin bed. In the sheet form, the sample and eluent are passed on one side of the sheet and a flowing regenerant is passed on the other side of the sheet. The sheet is in the form of an ion exchange 35 membrane partitioning regenerant from the effluent of chromatographic separation. The membrane passes ions of the same charge as the exchangeable ions of the membrane to convert the electrolyte of the eluent to weakly ionized form, followed by detection of the ions. 40
An improved membrane suppressor device is disclosed in EPA Pub. No. 75,371, published Mar. 30, 1983. There, a hollow fiber suppressor is packed with polymer beads to reduce band spreading. There is a suggestion that such packing may be used with other 45 membrane forms. Furthermore, there is a suggestion that the function of the fiber suppressor is improved by using ion exchanger packing beads. No theory is set forth as to why such particles would function in an improved manner. 50
Another suppression system is disclosed in EPA Pub. No. 69,285, published Jan. 12, 1983. There, the effluent from a chromatographic column is passed through a central flow channel defined by flat membranes on both sides of the channel. On the opposite sides of both mem- 55 branes are regenerant channels through which the regenerant solutions are passed. As with the fiber suppressor, the flat membranes pass ions of the same charge as the exchangeable ions of the membrane. An electric field is passed between electrodes on opposite sides of 60 the effluent channel which is stated to increase the rate of suppression. One problem with this electrodialytic membrane suppressor (EDS) system is that very high voltages (50-500 volts DC) are required. As the liquid stream becomes deionized, electrical resistance in- 65 creases, resulting in substantial heat production. Such heat is detrimental to effective detection because it greatly increases noise and decreases sensitivity. An
other problem is that the system generates excessive quantities of hydrogen gas.
An improved form of suppressor is described in EPA Pub. No. 180,321, published May 7, 1986. In this apparatus, the suppressor includes at least one regenerant compartment and one effluent compartment separated by an ion exchange membrane sheet. The sheet allows transmembrane passage of ions of the same charge as its exchangeable ions. Ion exchange screens are used in the regenerant and effluent compartments. Flow from the effluent compartment is directed to a detector, such as an electrical conductivity detector, for detecting the resolved ionic species. The screens provide ion exchange sites and serve to provide site to site transfer paths across the effluent flow channel. A sandwich suppressor is also disclosed including, a second membrane sheet opposite to the first membrane sheet and defining a second regenerant compartment. Spaced electrodes are disclosed in communication with both regenerant chambers along the length of the suppressor. By applying an electrical potential across the electrodes, there is an increase in the suppression capacity of the device.
Another EDS is disclosed in U.S. Pat. No. 4,403,039. An anode is disposed in the center of a tubular ion exchange membrane surrounded by a concentric annular flow channel and a tubular cathode.
An electrolytic membrane suppressor (EMS) is dis- • closed in Strong, D.L.; Dasgupta, P.K.; Anal. Chem. 1989, 61 939-945. That paper discloses single and double membranes in concentric tubular form. In the eluent which is suppressed, sodium ion passes to an annular regenerant solution container fed with water so that the effluent from such regenerant chamber is sodium hydroxide.
There is a general need for high purity eluents for liquid chromatography and a particular need in ion chromatography. Similarly, there is a need for a convenient way to generate gradient eluents of precise concentrations and timing. Gradient eluents are eluents at different strengths and concentrations used during the course of a single chromatography run. The use of gradient eluents for ion chromatography is described in Rocklin, R.D., et al. /. of Chromatographic Science, Vol. 27, p. 474, Aug. 1989; Qi, D., et al. Analytical Chemistry, Vol. 61, p. 1383, 1989; and Shintani, H., et al., Analytical Chemistry, Vol. 59, p. 802, 1987.
SUMMARY OF THE INVENTION
In accordance with the present invention, a method and apparatus has been provided for generating a high purity aqueous stream with selected ionic species-either either cation (e.g. sodium) or anion (e.g. sulfate) and suitable for use as a chromatography eluent. In one form, an eluent generating means defines a source channel and a product channel separated by a permselective ion exchange membrane including exchangeable ions of the same charge as the selected ionic species. The membrane allows passage of ions of the same charge as the ionic species but resistant to transmembrane passage of ions of opposite charge. Means is provided for applying an electrical potential between the source channel and product channel. The effluent from the product channel is directed to chromatographic separation means. Means is also provided for supplying liquid sample to the chromatographic separation means.
It is apparent that by using this system, only ions of the same charge as the selected ionic species flow across
the ion exchange membrane into the product stream since the membrane is resistant to transmembrane passage of ions of the opposite charge. This eliminates such oppositely charged ions which would otherwise interfere with the accurate analysis of the ionic constituents 5 of the sample during ion chromatography.
In the above single membrane device, gas is electrolytically generated in the product channel. For example, where sodium is the selected ionic species, the membrane is a cation exchange membrane and allows 10 the passage of positively charged ions only. The anodesource channel is positively charged and the product channel is negatively charged. In the product channel, water is electrolyzed to provide a source of hydroxide ion for the sodium which diffuses across the membrane. 15 Such electrolysis also generates hydrogen gas. The presence of such gas in the product channel can be detrimental to accurate chromatographic analysis. Means is provided for removing such gas from the product prior to use in chromatography. In one such 20 means, gas is removed from the product by passing it through a tube of hydrophobic gas diffusion membrane. This tube functions to permit the ready passage of gas but substantially prevents the transmembrane passage of liquid. 25
In another form of the device, two different membranes define two source channels, a positively charged, anode source channel and a negatively charged cathode source channel, and a product channel. For example, where sodium is the selected ionic species, the first 30 membrane is a cation exchange membrane and is adjacent to the anode source channel. Hydroxide in the anode source channel is oxidized and sodium ion passes across the cation membrane into the product channel. Oxygen gas produced by the anodic process substan- 35 tially remains in the anode source channel. The second membrane, an anion exchange membrane adjacent to the cathode source channel, allows the passage of negatively charged ions but substantially blocks positively charged ions. The cathode source channel is negatively 40 charged. Water in the second source channel is reduced to hydroxide ion and hydrogen gas and hydroxide ion passes across the anion exchange membrane into the product channel. Hydrogen gas produced by the cathodic process substantially remains in the cathode 45 source channel. Thus, largely gas-free sodium hydroxide is produced in the product channel.
In a preferred embodiment, the electrical current flowing between the source channel(s) and product channel is systematically varied by prior programming 50 to correspondingly vary the concentration of the selected ionic species in the product stream. Thus, this unit renders the device particularly effective for use as a gradient eluent generator.
BRIEF DESCRIPTION OF THE DRAWINGS 55
FIG. 1 is a schematic view of apparatus according to the invention for generating eluent and using it to perform ion chromatography.
FIG. 2 is an exploded view of the electrolytic cell 60 device including two source channels, on either side of an eluent product channel, each including a screen.
FIG. 3 is a side elevational view of an eluent generating means according to the invention.
FIGS. 4 and 5 are schematic side cross-sectional 65 views of single and double membrane eluent generating devices, respectively, according to the present invention.
FIGS. 6 and 7 are side schematic views of gas removal device according to the invention.
FIGS. 8 and 9 are a schematic cross sectional view of two different tubular forms of electrolytic cell.
DETAILED DESCRIPTION OF THE
The eluent generating means of the present invention will first be described in combination with ion chromatographic apparatus to which the eluent product is directed. For that purpose, for the analysis of anions on a chromatographic separation means, the eluent is an electrolyte, typically a cation hydroxide such as sodium hydroxide. Conversely, for the analysis of cations, the eluent typically is an acid such as hydrochloric acid. However, the eluent generating system of the present invention is also applicable to liquid chromatography forms other than ion chromatography. For example, it is applicable to liquid chromatography using an ultraviolet detector. In such instance, the eluent may be in other than an acid or base form, e.g. a salt such as KC1, KC104, KNO3 or the corresponding sodium salts.
Referring specifically to FIG. 1, a simplified ion chromatography apparatus is illustrated. The system includes chromatographic separation means, in the form of a chromatographic column 10, which is packed with chromatographic separation medium. In one embodiment, such medium is in the form of ion exchange resin. In another embodiment, the separation medium is a porous hydrophobic chromatographic resin with essentially no permanently attached ion-exchange sites. Such chromatography systems are described in EPA Publication 180,321, incorporated herein by reference.
Suppressor means 11 is in series with column 10 serving to suppress the conductivity of the eluent electrolyte in the effluent of column 10 but not the conductivity of the separated ions.
The effluent from suppressor means 12 is directed through a flow-through conductivity cell 14 for detecting the resolved ionic species in the sample in the effluent from suppressor means 12. A suitable data system is provided in the form of a conventional conductivity detector 16 for measuring the effluent from suppressor means 12 in conductivity cell 14. The effluent thereafter flows to waste. A suitable sample is supplied through sample injection valve 18. Eluent from an eluent generator generally designated by the number 20 is directed by pump 22 to chromatographic column 10.
The solution leaving chromatographic column 10 is directed to suppressor means 12 wherein the eluent is converted to a weakly conducting form. The effluent with separated ionic species then passes through conductivity cell 14.
In conductivity cell 14, the. presence of ionic species produces an electrical signal proportional to the amount of ionic material. Such signal is typically directed from cell 12 to a conductivity meter forming part of data system 16, thus permitting direct detection of the concentration of the separated ionic species.
The system of FIG. 1 is illustrated in the form of a system useful for anion analysis. Here, the selected ionic species of the eluent is sodium which is directed from a source 23 of sodium in hydroxide form to a anodesource flow channel of electrolytic cell 24. A product channel is fed from a container 26 of an aqueous product liquid (e.g. water) to the opposite side of an ion exchange membrane which separates the flow of the source sodium hydroxide from the water as will be