WO1994018555A1 - Sequential ion chromatography and conversion system - Google Patents

Abstract

Apparatus and method for ion chromatography having a chromatography column (10) followed by a suppressor (11) for converting the eluent electrolyte to weakly ionized form and converting analyte ions to acid or base form. First detection of analyte ions occurs in a first conductivity detector (12) followed by conversion of the analyte ions in acid or base form to salt form in a salt converter and subsequent detection in a second conductivity detector (32). Comparison of signals from the two detectors (12, 32) provides additional information about the analytes.

Description

SEQUENTIAL ION CHRO ATOGRAPHY AND CONVERSION SYSTEM

BACKGROUND OF THE INVENTION

The present invention relates to a method and apparatus using ion chromatography ("IC") followed by chemical conversion and detection of the sample ions.

Ion chromatography is a known technique for the analysis of ions which typically includes a chromatographic separation zone using an eluent containing an electrolyte, and an eluent suppression stage, followed by detection, typically performed by a conductivity detector. In the chromatographic separation stage, ions of an injected sample are eluted from a separation column. In the suppression stage, electrical conductivity of the eluent electrolyte is suppressed but not that of the separated ions. This can be accomplished so long as the separated ions are not derived from very weak acids or bases and so can be determined by conductivity detection. This general technique is described in U.S. Patent Nos. 3,897,213, 3,920,397, 3,925,019 and 3,956,559.

The above patents describe suppression or stripping of electrolyte using an ion exchange resin bed. In an improved form of suppression, a charged membrane in the form of a fiber or sheet is used in place of the resin bed. In sheet form, the sample and eluent are passed on one side of the sheet with a flowing regenerant on the other side of the sheet. The sheet comprises an ion exchange membrane partitioning the 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.

One effective form of suppressor is described in U.S. Patent 4,999,098. In this apparatus, the suppressor includes at least one regenerant compartment and one chromatographic effluent compartment separatedby 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 so that suppression capacity is no longer limited by diffusion of ions from the bulk solution to the membrane. 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. The patent discloses a typical regenerant solution (acid or base) flowing in the regenerant flow channels and supplied from a regenerant delivery source. In a typical anion analysis system, sodium hydroxide is the eluent and sulfuric acid is the regenerant. The patent also discloses the possibility of using water to replace the regenerant solution in the electrodialytic mode.

There have been a number of attempts to perform IC without the necessity of a standard (sometimes termed "standardless" or "solute independent" analysis) . Such techniques generally use two different detectors with the same analyte by analyte conversion or using different eluents. The signals are compared to provide analytical information in addition to that provided by each IC method alone. For example, in Wilson, S. A. et al., Anal. Chem. 1984, Vol. 56, 1457, a system is described in which two different eluents, one of high conductance and one of low conductance, are used in two different IC systems using two analyte samples. The signals from the two detectors are compared. For anion analysis, the paper suggests converting all of the analyte anions to HC1 form prior to detection to normalize peak responses. In a similar system, Renn, C.N., et al.. Anal. Che .. 1989, Vol. 61, 1915, two signals are generated using two separate IC systems with different eluents for the purpose of universal calibration. Both approaches require two separate IC systems. Also, there is a lack of practical eluents of sufficiently different equivalent conductance for commercial use.

In Berglund, I., et al. Anal. Chem. 1991, Vol. 63, 2175, another multiple detector system is described. Here, conventional IC is performed using a first conductivity detector. The effluent from that detector is passed sequentially through cation exchange and anion exchange conversion zones. For anion analysis, the effluent from the first detector is in the usual IC form of HX (wherein X is the analyte anion) as it exits from the suppressor. Two different types of convertors are disclosed. In a sequential packed column form, the effluent first passes cation (sodium) exchange resin and then anion (hydroxide) exchange resin, resulting in sequential conversion first to NaX salt and thereafter to NaOH. A permselective membrane-type converter is also disclosed for such sequential conversion. After conversion, the ion conductivity of the sodium hydroxide is measured in the second detector and compared to the ion conductivity of the first detector. The paper states that the data reveals peaks due to very weak acids hidden in the suppressed base line or overlapped with strong acid peaks. It further states that this method allows an estimation of the pK of the analyte peak and permits approximate quantitation without standards. Problems with that system include the following: (1) incomplete conversion of the acid form analyte to NaOH due to differences in ion exchange selectivity between hydronium and sodium, and analyte anion and hydroxide on the cation and anion exchange resins respectively; and (2) analyte band dispersion in the ion exchange columns must be compensated for when ratioing the signals from the two detectors. For weak acids, for example, it can be more of a problem, because there is less free hydronium ion available to exchange for sodium ion.

SUMMARY OF THE INVENTION

In accordance with the invention, apparatus and methods are provided using IC principles in which different detectors provide useful comparative signals. Specifically, in one form of the apparatus, separating means, typically in the form of a chromatographic resin column, separates the analyte ions in the presence of an eluent comprising electrolyte. The effluent from the separating means flows through suppressor means for converting the electrolyte to weakly ionized form and the analyte ions to acid or base form. The suppressed effluent flows through a first detector for detecting the conductivity of the ionic species and generates a first signal. This portion of the system is conventional suppressed IC.

The effluent from the first detector flows through a salt convertor for converting the analyte ions in acid or base form and to salt form. Then, the conductivity of the salt form of the analyte is measured in a second detector means and a second signal is generated. Preferably, the first and second signals are analyzed to represent a defined relationship between the output signals.

In one embodiment, the analyte ions in acid or base form are converted to their corresponding salts in a single conversion with salt-forming ions of opposite charge. For example, for analyte anions represented by "X", and using Na* ion, NaX is measured in the second detector means. This will be referred to herein as the "single conversion mode" or "single conversion".

A preferred salt convertor minimizes dispersions which could skew peak ratios of the single conversion type. A particularly effective single conversion convertor is an on-line microelectrodialytic ion source which supplies the salt-forming ion through a membrane. It includes a salt-forming ion source channel, a suppressor effluent flow channel and a permselective ion exchange membrane partitioning the two channels. The membrane includes exchangeable ions of the same charge as the salt-forming ions and is resistant to transmembrane passage of the ionic species. An electrical potential is applied between the ion source channel and suppressor effluent flow channel. The latter channel is in fluid communication with the effluent from the suppressor.

In operation, the signal generated in the first conductivity detector for the acid or base form of the analyte is evaluated with the signal generated in the second ion conductivity detector for the salt form of the analyte to provide extremely useful information.

Other single conversion convertors include the use of an ion exchange membrane barrier without electrolysis, but with external acid or base concentrations sufficient to overcome the Donnan barrier. Still other systems include the use of a porous membrane barrier using the application of current or differential pressure to drive the acid or base salt-forming ions into the suppressor effluent flow channel.

Single conversion may also be accomplished by flowing the suppressor effluent stream through an ion exchange medium such as a column of an ion exchange resin bed having exchangeable ions of opposite charge to the analyte ions.

In another aspect of the invention referred to as "double conversion mode" or "double conversion", the analyte ions are twice-converted. In this instance, the analyte ion is converted to a salt of (a) the same type of counterion as in the single conversion mode, and (b) a common single ion of the same charge as the analyte ion. This can be accomplished by simultaneous ion exchange of the acid of base form of the analyte ions with the selected anion and cation. In one embodiment using a permselective membrane, the suppressor effluent flows in a central channel flanked by two ion source channels, one including anions and the other including cations. Permselective membranes separate the ion source channels from the suppressor effluent flow channel and include exchangeable ions of a type which permit transport of such cations and anions into the suppressor effluent flow channel to accomplish double conversion. In another simultaneous double conversion, the suppressor effluent flows from the first detector through ion exchange medium such as an ion exchange resin bed, including exchangeable anions and cations of the same type desired as in the permselective membrane.

Double conversionmay alsobe accomplished sequentially. In one embodiment, the suppressor effluent flows from the first detector sequentially through two ion exchange columns of opposite charge. For example, the first column includes a common, single ion of the same charge as the analyte ions so that a converted acid or base with a common anion or cation is formed in the first column which is passed to the second column for conversion to a salt. However, the order of the columns may be reversed.

Similarly, a permselective membrane system may be used for the sequential double conversion embodiment. The membrane convertors can be in either order like the sequential ion exchange columns.

BRIEF DESCRIPTION OF THE DRAWINGS Figures l and 6 are schematic views of apparatus for performing the ion chromatography-based analysis of the present invention using an on-line salt convertor. Figure 2 is a schematic expanded view showing the reactions in a salt convertor of the present invention for single conversion mode anion analysis.

Figure 3 is an alternate schematic flow diagram using a salt generator.

Figures 4 and 5 are cross-sectional views of two different forms of single conversion mode salt convertor.

Figure 7 is a plot of conductance v. time for a sample mixture of strong and weak acid anions.

Figure 8 further plots of detector outputs according to the invention.

Figure 9 is a comparison of simulated and experimentally observed response.

Figures 10 and 11 illustrate dual conversion mode salt convertors.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The system of the present invention is useful for determining a large number of ionic species so long as the species to be determined are solely anions or solely cations. A suitable sample includes surface waters, and other liquids such as industrial chemical wastes, body fluids, beverages such as fruit juices and wines and drinking water. When the term "ionic species" is used herein, it includes species in ionic form and components of molecules which are ionizable under the conditions of the present system. The purpose of the suppressor stage is to reduce the conductivity and noise of the analysis stream background while enhancing the conductivity of the analytes (i.e. , increasing the signal/noise ratio) particularly forwell ionized species, while maintaining chromatographic efficiency.

Referring to Figure 1, a simplified apparatus for performing the present invention is illustrated. The system includes chromatographic separation means, typically in the form of a chromatographic column 10, which is packed with a chromatographic separation medium. In one embodiment referred to above, 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. This system is used for mobile phase ion chromatograph (MPIC) as described in U.S. Pat. No. 4,265,634. An ion exchange site-forming compound, including hydrophobic portion and an ion-exchange site, is passed through the column and is reversibly adsorbed to the resin to create ion- exchange sites.

Arranged in series with column 10 is suppressor means 11 serving to suppress the conductivity of the electrolyte of the eluent from column 10 but not the conductivity of the separated ions. (This system works best for strong acids and strong bases.) The conductivity of the separated ions is usually enhanced in the suppression process.

The effluent from suppressor means 11 is directed to a first detector in the form of conductivity cell 12 for detecting all the resolved ionic species therefrom, preferably in the form of a flow-though conductivity cell. A suitable sample is supplied through sample injection valve 13 which is passed through the apparatus in the solution of eluent from eluent reservoir 14 drawn by pump 15, and then is passed through the sample injection valve 13. The solution leaving column 10 is directed to suppressor means 11 wherein the electrolyte is converted to a weakly conducting form. The effluent with separated ionic species, treated by suppressor means 11 passes through conductivity cell 12.

In conductivity cell 12, the presence of ionic species produces an electrical signal proportional to the amount of ionic material. Such signal is typically directed from the cell 12 to a conductivity meter, not shown, thus permitting detection of the concentration of separated ionic species.

Suppressor means 11 includes a regenerant reservoir 16 or other source of regenerant solution which is directed to at least one flow-through regenerant channel in an ion-exchange membrane device 17. A suitable membrane device is described in detail in U.S. Pat. 4,999,098, incorporated herein by reference. Regenerant from reservoir 16 flows through a pump 18 into conduit 20 to supply the regenerant to the regenerant flow-through passages and then to waste through conduit 22. The effluent flows from chromatographic column 10 to suppressor means 11 through conduit 23, and from the membrane device to the conductivity detector through conduit 24. Any form of suppressor means may also be employed so long as it converts the electrolyte of the effluent to weakly ionized forms and the ionic species to acid or base form (e.g. the less desirable ion exchange resin bed described above) . After passing through conductivity detector 12, the effluent flows through salt conversion means (salt convertor 30), a second conductivity detector 32, and then to waste.

In salt convertor 30, the analyte ions which had been converted to acid or base form in suppressor 11 are converted into salt form by reaction with the counterion of an acid or base. For purposes of this description, the system will be described for anion analysis in which case the counterion is sodium which is supplied to the analyte stream to convert the anions to sodium salts.

For anion analysis, cations other than sodium may also be employed to convert the anions to salt form (e.g. alkali metals such as lithium or potassium) , alkaline earths (such as calcium or magnesium) as well as ammonium ions. For cation analysis, acids provide the anion counterions, e.g. chloride, nitrate, sulfate, or methane sulfonate. Such counterion anions preferably have the characteristics of being easily transported through the membrane in the salt convertor.

SINGLE CONVERSION MODE

The single conversion mode will be described first. For example, in anion analysis wherein the analyte anion is represented by X^", and M^* represents the counterion (cation) , the X^' analyte is converted to a common anion so that the final product is NaA in which A^" represents the converting anion.

It is important that the amount of acid or base introduced in the salt convertor is relatively small so that background conductance is not excessive. For this purpose, the concentration of sodium hydroxide provided to the analyte stream should be no larger than required to convert the maximum expected concentration of all analyte ions to salt form. A suitable sodium ion concentration is supplied by a source of sodium hydroxide at a concentration on the order of 10 to 1000 μM and preferably 50 to 150 μM sodium hydroxide. In this way, detection with a low background of sodium hydroxide can be performed regardless of the eluent sodium hydroxide concentration (including deliberate variation of the eluent concentration during a gradient run) .

The effluent from salt convertor 30 is passed to conductivity detector 32 in which the ionic species salts are detected. In a preferred embodiment, suitable electronics is provided, not shown, for interrelating the signals from conductivity detector 12 and conductivity detector 32 for providing unique information not available from either technique alone. Such electronics receives the two signals as input signals and provides a defined relationship between the input signals. Such information includes information from signal ratioing such as peak purity, analyte pK_a estimate, analyte valency and approximate quantitation without specific calibration.

In one preferred form, salt convertor 30 uses the principle of an electrodialytic generator as disclosed in U.S. Pat. 5,045,284, incorporated herein by reference, but constructed on a microscale. Because the amount of sodium hydroxide utilized is very small, the requisite current also is very small. Insufficient gasses would be generated to require removal as may be necessary in the macroscale counterpart as disclosed in the above patent. An on-line microelectrodialytic generator form of salt convertor is illustrated in Figure 2 for anion analysis and includes sodium hydroxide as the source of salt converting ion (sodium) . Salt convertor 30 includes a housing with parallel side walls 32 and 34 defining a flow-through opening. A permselective ion exchange membrane 36 partitioned ion source channel 38 from suppressor effluent flow channel 40. Membrane 36 includes exchangeable ions of the same charge as the salt-forming (sodium) ions, i.e. positive charge, and is resistent to transmembrane passage of the negatively charged ionic species to be detected. Means is provided for applying an electrical potential between salt- forming ion source channel 38 and suppressor effluent flow channel 40. For anion analysis, the salt-forming ion source channel is positively charged by anode 42 and the suppressor effluent flow channel 40 is negatively charged under the influence of cathode 44.

Such membrane salt convertors may be of any convenient geometry. For example, the membrane may be flat as illustrated in Figure 2 or cylindrical as illustrates in Figures 4 and 5.

In operation, the effluent from conductivity detector 12 flows through suppressor effluent flow channel 40, downwardly as illustrated, in the form of an acid designated by the symbol HX. Sodium hydroxide is fed to ion source channel 38, preferably countercurrent to flow in suppressor effluent flow channel 40, to supply the sodium ion to convert the anions in acid form to the salt NaX. The structure, mode of operation, reactions, and transmembrane transport of sodium ion are the same for the membrane devices set forth in U.S. Pat. 5,045,204 with the exception that the transmembrane passage of sodium ions also form a salt in the suppressor effluent flow channel with the ionic species, as well as pure sodium hydroxide as in the product channel of the patent. As previously mentioned, the present system is on a microscale, and so there is no need to remove generated gasses.

Suitable flow rates for a typical system are 0.1 ml/min to 3.0 ml/min. A suitable concentration of sodium ion in the ion source channel depends on the concentration of the analyte anions to be converted to salt form. Typical concentrations are on the order of ImM to lOmM sodium hydroxide in the ion source channel.

Only a relatively low current flow is required in order to provide sufficient sodium ion to convert the analyte anions into salt form. Suitable currents for this purpose are on the order of 50 μA to 500 μA.

The on-line salt conversion system may also be employed for the analysis of cations. In this instance, the cations are converted to hydroxide form in the suppressor 11 and passed through suppressor effluent flow channel 40. The membrane 36 is an anion exchange membrane. An acid flows through the ion source channel with its characteristic anion passing through the anion exchange membrane to the suppressor effluent flow channel to neutralize hydroxide from the analyte cation and form a salt. Suitable operating parameters are the same for the cation analysis system as the anion analysis system.

Another on-line system in which a base or acid can be added without volumetric dilution uses a small nonelectrolytic cation exchange membrane barrier separating the suppressor effluent and the salt-forming ion source channels in a reactor with an external NaOH concentration sufficient to overcome the Donnan barrier. The parameters for such a system are described in Dasgupta, P.K. jln "Ion Chromatography", Tarter, J.D., Ed., Marcel-Dekker, New York, 1987, 191-367.

A major advantage of the above on-line systems are that there are essentially no dilution effects because the salt-forming ions pass through the membrane without an accompanying volume of carrier solution.

Yet another system employs a non-charged, porous membrane barrier (e.g. dialysis membrane) separating the suppressor effluent from the ion source channel wherein current is applied between the two channels across the membrane in an electrodialysis system. (Strong, D.L. ; Dasgupta, P.K. ; Friedman, K. ; Stillian, J.R. Anal. Chem. 1991, Vol. 63, 480-486). The pores of the membrane "leak" acid or base for salt conversion. Here, volumetric dilution and a change in flow rate must be considered in analyzing the data.

In yet another type of porous membrane salt convertor the pores are sufficiently large to permit pressurized introduction of acid or base across the membrane at a constant rate (Cassidy, R.M. et al.. Anal. Chem. 1987, 87, 59).

The amount of requisite salt-forming ion (e.g. sodium) is relatively low. Thus, a source of the salt-forming ion (e.g. sodium hydroxide) , may be connected as through a mixing tee to the line between conductivity detectors 12 and 30. In this instance, the salt convertor is simply a stream of sodium hydroxide fed to the suppressor effluent after conductivity detector 12 but before conductivity detector 32.

A convenient system of the foregoing type feeding a constant flow of salt-forming ion to the system is illustrated in Figure 3. It utilizes a icroelectrolytic generator of the structure and mode of reaction illustrated in U.S. Pat. 5,045,204, but on a micro scale similar to that described for Figure 2. After detection in conductivity detector 12, the suppressor effluent is directed to mixing tee port 50. For anion analysis, sodium hydroxide generated in microelectrodialytic generator 52 is fed to the mixing tee port 50 for mixing with the suppressor effluent in mixing coil 54 to provide sufficient residence time for salt conversion. The salt is then directed to the second conductivity detector 32 and then to waste. Water and sodium hydroxide are directed through generator 52 in the manner set forth and in U.S. Pat. 5,045,204 for use as the source of sodium hydroxide in the mixing tee. The generator permits a convenient change of concentration of sodium hydroxide to meet a corresponding change of analyte concentration. As in the patent, this can be accomplished by varying the current.

One advantage of using this form of acid or base reagent introduction over the introduction of a pre-made reagent is a significant decrease in detector background sensitivity to flowrate changes. If a pre-made reagent at a constant concentration is introduced any change in the flow results in direct and linearly proportional change in the background conductance of the mixture after the tee. With an electrodialytic generator operating at constant current the amount or mass of the reagent generated is constant. Any change in the flowrate does not change the amount of NaOH introduced to the main stream. Since the feed flow is much smaller than the main stream, the sensitivity of the background conductance to fluctuations in the flowrate of the electrodialytically generated reagent flow is substantially reduced.

For the system of Figure 3, a suitable salt-forming ion stream for anion analysis includes sodium hydroxide at a concentration of 0.5 mM to 10 mM and in a ratio of 1:5 to 1:100 to the suppressor effluent. The dilution effect is relatively minor in view of the low requirements for salt-forming ion. Volumetric dispersion is largely offset by the concommitant increase in flow rate and any other dilution effects can be accommodated by suitable electronics.

If desired, the generator 52 may be replaced by a constant-flow source of sodium hydroxide. This is cheaper to construct but is less flexible and contributes to greater background noise.

A significant advantage of the present invention is that it utilizes a conventional suppressed IC system for one of the analyses. By using a hydroxide eluent, the effluent from the suppressor has extremely low background. Also, the system permits facile use of a gradient eluent for IC, e.g. of the type set forth in Strong and Dasgupta, Anal. Chem., 1989, 61, 939. The present system is compatible with a gradient hydroxide elution scheme because there is a constant background conductance in the second detector regardless of the eluent concentration used. Yet another form of the single conversion salt convertor comprises an ion exchange medium suitably in a column, preferably packed with ion exchange resin particles. The particles include exchangeable ions of opposite charge to the analyte ions. The same exchangeable ions (e.g. sodium) , for anion analysis may be used as described above with respect to the membrane device 17. One problem with the resin bed is that the volumetric displacement must be taken into account by the electronics when comparing the signals from the two detectors. Comparable flow rates and analyte ion concentrations may be employed as discussed above with respect to the membrane device embodiments.

DOUBLE CONVERSION MODE It may be desirable in some instances to make a doubly converted salt in the salt convertor as illustrated in Berglund, I. and Dasgupta, P.K., Anal. Chem. 1992, 64, 3007-3012, incorporated herein by reference. As set forth above, double conversion refers to conversion of the analyte to a salt of (a) a counterion (e.g. Li⁺) as set forth above with (b) analyte ions converted to ions of the same type (e.g. F^") . For example, assuming anion analysis of X^" analyte, the analyte ion is eluted in the form HX. The dual mode convertor converts the analyte counter-ion to H^* (a cation counterion of the type set forth above) and A^" is a single common anion selected for its desired properties as set out below. The order of conversion is not critical. For example, the conversion may take place simultaneously or sequentially. For sequential conversion, an acceptable order is to convert the analyte ion to the common converting ion and thereafter to convert the acid or base to a salt. For anion analysis the equation of this conversion is as follows: HX → HA → MA ( 1 )

Alternatively, the order may be reversed and conversion may take place according to the following equation:

HX → MX → MA (2)

The same principle applies for cation analysis. The following description sets forth certain principles and modes of operation for the dual conversion system. Conversion is suitable performed by simultaneous or sequential contact with anion exchange and cation exchange membrane devices or resins.

An example of the above system is for analysis of the analyte acetate (Ac) which entered the salt convertor in the acid form as HAc and is doubly converted to LiF. This doubly converted salt is selected because it is an excellent compromise between ion exchange selectivity, which affects the completeness of conversion to the salt, and equivalent conductance of the salt measured at the second detector as described in the last named Berglund and Dasgupta paper. For the present system, LiF appears to provide the lowest background and highest sensitivity in the second detector for the doubly converted salt and hence, the best detection limits. However, other salt-forming ions may also be employed, including anions and cations used for single conversion. For example, for anion analysis, sodium may be used in place of lithium and chloride in place of fluoride. Thus, salts other than LiF include LiCl, NaCl, and NaF. The principles of dual mode conversion described above also apply to cation analysis. Referring to Figure 10, the reactions in a simultaneous dual conversion mode salt convertor (an anion analysis) is illustrated using two permselective membranes. The schematic system is illustrated for a flat membrane but the principles apply to the concentric tube approach as illustrated in Figure 11 below.

As illustrated, the system includes sidewalls 100 and 102 defining a first ion source channel 104 for convertor ion, F^" as illustrated, of the same charge as the analyte anion separated by an anion exchange membrane 106 from the suppressor effluent flow channel 108 from the first conductivity detector (designated 12 in Figure 1) . Suppressor effluent flow channel 108 is separated on its opposite side by cation exchange membrane 110 from the second ion source channel 112 for counterion (Li⁺ as illustrated) . In this device, F^" in first ion source channel 104 exchanges with the analyte anions in channel 108 and Li⁺ exchanges with the hydronium ion in the suppressor effluent to form LiF which is detected in the second conductivity detector 32 of Figure 1. In this instance, the fluoride ion is supplied by a feed of NH₄HF₂(NH^F+HF) , and LiF.

HF is added to the anion source channel so that as the weak acid analyte enters the anion source channel as it is replaced with F^", the acid form of the analyte is formed which is at least partially un-ionized HX and this maintains the concentration gradient for the weak acid analyte X^" from the suppressor effluent flow channel to the anion source channel. LiOH is added to the cation source channel also to maintain the concentration gradient for the co-ion, hydronium ion, from the suppressor effluent flow channel to the cation source channel as it is replaced by Li⁺ from the cation source channel. The concentration gradient for hydronium ion is maintained since hydronium ion is consumed in the neutralization reaction with OH^" in the cation source channel. An excess of LiF is added to both the anion and the cation source channels to prevent the LiF formed in the suppressor effluent flow channel from diffusing back to the anion and cation source channels by maintaining a positive concentration gradient toward the suppressor effluent flow channel. Typical flowrates for the anion and cation source flow channel solutions is 1 to 2 mL/min.

The concentration of the fluoride should be sufficient to provide substantially complete conversion of the analyte ions without any substantial increase of anion in the suppressor effluent flow channel which could provide undesirable background noise for detection. Suitable fluoride concentrations are 0.1 mM to 100 mM. Suitable concentration of salts in the first or anion source channel are about 0.1 mM to 100 mM LiF, 0.1 mM to 10 mM NH4F, and 0.1 mM to 10 mM HF. Typical concentrations are 10 mM LiF, 1 mM NH_AF, and 1 mM HF.

Referring to the second ion source channel 112 (cation as illustrated) a combination of the cation hydroxide and a salt of the anion in the anion source channel are used. Suitable concentrations for the cation source channel are about 0.1 mM to 100 mM LiF and 0.1 mM to 10 mM LiOH, typically 10 mM LiF and 2mM LiOH.

Simultaneous conversion form of the dual salt convertor mode of the present invention may also use ion exchange medium, suitably ion exchange resin, in an ion exchange column including both cation and anion exchangeable ions of the foregoing type. Thus, the preferred ultimate salt is LiF. Suitable combination ion exchange column of the foregoing type is selected according to the following parameters.

The simultaneous cation/anion-exchange approach yields superior overall exchange efficiencies for very weak acid eluites, relative to sequential ion-exchange scheme. Conductometric detection in the suppressed ion chromatography mode and after conversion of the eluite acid to LiF produce two-dimensional data that can be processed to improve quantitation of very weak acids and provide information about the pK_a of unknown eluites and detect the presence of one or more analyte in a chromatographic peak.

As set forth above, dual conversion may also be performed sequentially. Using ion exchange columns, the cation and anion exchange resins would be separated so that the suppressor effluent flows sequentially through the two columns. Either order of conversion means may be employed.

The foregoing principles of sequential dual mode ion salt conversion apply to membrane type devices. Dual conversion by sequential membrane devices is performed solely by ion exchange of the same general type described above with respect to the simultaneous conversion illustrated in Figure 10. Microdialytic generation of acid or base (as illustrated in Figures 4 and 5) combined with porous membrane technology described above are less preferred because porous membranes allow bulk liquid to enter the suppressor effluent stream and the resulting dilution must be accounted for by the comparing electronics. In order to illustrate the present invention, the following examples of its practice are provided.

Example 1 (Single Conversion Salt Convertor) Referring to Figure 4, a suitable form of salt convertor 5. is illustrated in the form of a microelectrodialytic acid or base generator. Such generator operates on the principles set forth in U.S. Pat. 5,045,204. It includes a jacket tube 60 suitably formed of an inert rigid machinable or moldable material (e.g. stainless 0 steel or PEEK) with end plugs 62 suitably formed of same. A suppressor effluent conduit generally designated by the number 64 is provided internally of and coextensive with jacket tube 60 in the form of connecting tubes (e.g. formed of Teflon^® and 0.3mm ID) 5 passing through plugs 62. Conduit 64 is formed of connecting tube segments 64a, 64b, and 64c. Segments 64b and 64c are connected by overlapping tubing 66 (e.g. formed of polyvinyl chloride pump tubing) . The salt- forming ion (e.g. from an aqueous sodium hydroxide 0 stream) is directed through opening 68 into annular chamber 72 is formed between jacket 60 and conduit 64 and exits through opening 70. A section of permselective membrane 74, suitably formed of an ion exchange membrane produced under the trademark Nafion^® 5 overlaps the gap between conduit segments 64a and 64b. For anion analysis, the ion exchange membrane is in a cationic form permitting passage of sodium ion but blocking passage of the analyte anion flowing through conduit 64. (In an alternate configuration, membrane 0 74 is composed of a material with extremely small pores such as cellulose acetate, polyacrylonitrile, polysulfone or polypropylene.) External to membrane 74 is a spirally wound electrode 70 (e.g. formed of platinum wire) serving as an anode connector to an external power source, not shown. Connected to the same power source is a cathode 78 disposed internally of conduit 64 to extend along the flow path of the generator.

A specific form of the design of Figure 4 is as follows. Nafion^® 020 tubing (ca. 0.4 i.d., 0.5 o.d., Perma- Pure Products, Toms River, NJ) is connected to PTFE tubing with the help of elastometric poly (vinyl chloride) (PVC) pump tubing. Platinum wire, 100 μm in diameter, is put into the lumen of the membrane to function as the cathode and brought out through the wall of the tubing. Similarly, 100 μm Pt-wire is wrapped around the membrane to function as the anode. The assembly is jacketed in an external jacket and 10 mM

NaOH was allowed to flow under gravity through this at a flow rate of < 1 mL/min. The active length of the

■ membrane was 1 cm. The electrodes are connected to the CCG.

In operation, the suppressor effluent passes through suppressor effluent conductor 64 and the sample anion in acid form are converted to salt by sodium from the sodium hydroxide passing through the permselective membrane into the anion analyte.

It should be recognized that the purpose of the ion exchange membrane in the above example is to selectively introduce the Na⁺ cation from the ion source. Direct contact of the eluite cation (H⁺) with the membrane can result in ion exchange taking place in addition to the constant electrodialysis. Consequently, it is preferable to reduce the direct contact of the suppressor effluent stream with the ion exchange membrane. Thus, in an alternative embodiment, a polysulfone membrane tube may be disposed within the ion exchange membrane to reduce direct contact with the suppressor effluent and the ion exchange membrane.

One such design illustrated in Figure 5 is identical to that of Figure 4, except that the Nafion^® tube is first swelled in ethanol and a porous polysulfone membrane tube 79 (0.2 μm pores, 300 μm i.d., 400 μm o.d., Microgon, Inc., Laguna Hills, CA) is inserted within it. The device of Figure 5 has a small active length of 2 mm.

Example 2 (Full Single Conversion System)

A suitable more detailed system application is illustrated in Figure 6. The pump 80, injection valve 82 (25 μL) , chromatographic column 84, suppressor 86, and first detector 88 are components of an ion chro atograph of the DX-100 type ion chromatograph (Dionex Corporation, Sunnyvale, CA) . All chromatography is conducted with an NaOH eluent (ca. 19 mM except as mentioned) at a flow rate of 1.0 mL/min on a AS5A-5μ column. Suppressor 88 is an externally resin packed filament-filled helical Nafion^® membrane device bathed externally with 20 mM dodecylbenzenesulfonic acid (as described in Gupta, S., et al. J. Chromatogr. Sci.. 1988, Vol. 26, 34). The detector effluent proceeds through a microelectrodialytic NaOH generator 90 (MNG) of the foregoing type powered by a constant current generator 92 (CCG) and then through the second conductivity detector 94. Suitably, the data from both detectors is analyzed by computer 96, suitably a 80386 based PC using AI-450 software and an ACI interface. (Dionex Corporation) . The CCG is designed to operate at sub-mA current levels and offers switch-selectable ranges. Except for the choice of the operating current range and the availability of a higher voltage to be applied to the MNG, the CCG electronics is functionally identical to that described in Strong, D.L. , et al. Anal. Chem. 1991, Vol. 63, 480.

The experimental scheme of Figure 6 shows excellent baseline stability. A desired background conductance of 20-30 μS/c was assumed. This corresponds to approximately 10^"* M NaOH, which means injected sample concentrations of up to at least 10^"3 N could be handled in a straightforward manner, assuming a typical chromatographic dilution factor of 10 at the analyte peak maximum. The generator current necessary to achieve a background conductance of 25 μS/cm was approximately 160 μA — this corresponds essentially to Faradaic current efficiency. The voltage required for this current injection varied from 2.4 V to 7 V depending on the dimensions of the generator device and whether a microporous membrane was interposed between the electrodes and the ion exchange membrane. The baseline noise at this level is <20 nS/cm. The system is stable over a long period and background conductivities are repeatable at the same current level on a day-to-day basis. Good chromatography can be done at this noise level and attractive limits of detection attained. Dispersion induced by the device was measured with the device in place but without NaOH introduction. The dispersion was negligible.

Example 3 (Single Conversion)

A typical chromatogram at low analyte concentrations

(25 μM each anion) is shown in Figure 7. The five respective peaks are labeled a-e. The two detector outputs have been synchronized with respect to time. Peak a is incompletely resolved fluoride and borate, in the first detector output there is only a hint of two species being present — the second detector output quite clearly shows two components. Peak b is similarly a mixture of chloride and glyoxylate, in this case the first detector output reveals no hints about the incomplete resolution. The second detector output however, shows the presence of two components. Peak c is due to C0₂ dissolved in the sample, the response is virtually invisible in the first detector but clearly evident in the second detector. This is typical of very weak acids. Peak d produces comparable and significant response on both channels. Peak shape is the same on both channels indicating that the peak is pure. This is also indicated by a constant ratio of the two signals across the peak.

It is possible to draw further inferences if this is indeed a pure component. First, at least one of the dissociation constants is quite low, permitting significant ionization as gleaned from the first detector output. Second, the anion is probably not a monoprotic acid — in that case the second detector output would not have been comparable to the first detector output (for a monoprotic acid, the ratio of (λH^* + λX^") to (λOH^" - λX^") is minimally 1.8, typically - 2, and for small anions, like Cl^", as high as 3.4) . One suspects therefore that the anion is a diprotic acid (at least) where the second proton is incompletely dissociated and does not contribute much to the first detector signal but is fully ionized in the second detector output. This appears to put an upper limit on pK₂, the anion could not be, (e.g. , S^2") where pK₂ is too high for the proton to be removed in 10^"4 M NaOH. The anion responsible for peak d is arsenate, with pK values of 3.33, 6.98 and 11.50 (for pK, - pK₃, respectively). The third proton plays no role in either detector output. Finally, peak e in the chromatogram is much stronger in the first detector output relative to the second detector output. One therefore suspects the presence of a strong acid. The peak is due to a mixture of malonate and nitrate. Results suggest that peak e may not be a pure peak because the peak shapes of the two outputs are not the same.

Further information can be gained from a more quantitative treatment of the data. Ratio values of the two detector outputs can indicate peak purity as indicated above. However, a complimentary and often superior approach may be to plot one detector output against another. To compute ratio values, it is necessary to subtract the background exactly across the peak. This is difficult at low levels where the background noise may be appreciable. Consequently, at the edges of the peak where the signal value approaches zero, noise contributions make ratio calculations unreliable. Plotting one signal against another for selected blocks of the chromatogram is computationally faster, provides more visual information and is more immune to random noise induced errors. Ideally for a pure peak, all the points should fall on the same straight line, the slope of which is equal to the absolute value of the ratio observed in a ratiogram. Such plots for the respective regions a-e in the chromatogram of Figure 7 are shown in Figure 8a-8e. Because of the different response intensities for the peaks, the scaling of the axes in 8a-8e are not the same but relative ordinate/abscissa scaling is constant so that the slopes can be visually compared. The more vertical the slope of a plot, the lower is the dissociation constant of the acid analyte.

Only in Figure 8c (carbonate) we see the ideal pattern of all points falling on the same straight line. And a complete crossover indicating two clear components is seen only in Figure 8a. This type of pattern, i.e., some form of a (considerably distorted) figure eight pattern is always observed when at least one of the outputs contains two clear peaks for the region plotted. In plots 8b-8d, while all the points do not fall on a straight line, even for a pure peak, it has been consistently observed that a pure peak is still characterized by the fact that a straight line will bisect the plotted points in a highly symmetric fashion.

Results -

In the desired system the output of the first detector favors the strong acid eluites while the output of the second detector favors the weak acid anions. Weak and very weak acid anions such as sulfide, carbonate, silicate, borate, cyanide, arsenite all produced excellent responses on the second detector output. Extensive calibration data was gathered for borate, silicate and arsenite (pK_a > 9 for all three) in the injected concentration range of 0-1 mM (typically 5 concentration points, triplicate injection at each concentration) and resulted in linear r² values ranging from 0.996 to 0.999 and a LOD of between 2 and 3 μM for each of these analytes based on the S/N = 3 criterion. Considering that these analytes cannot be detected even at the mM level in conventional suppressed IC, the present approach is therefore superior to either conventional suppressed or single column IC in terms of the broad spectrum of eluite pK_a to which it is applicable and in terms of the levels which it is capable of detecting.

Example 4 (Single Conversion) Should the eluite peak concentration exceed the background NaOH concentration, unusual behavior may result. Although this situation is easily corrected, (e.g. by sample dilution) it is instructive to elucidate this behavior. It may be intuitively reasoned that for a strong acid eluite, (e.g. HC1) , the second detector signal will produce a negative dip until all the NaOH is neutralized to NaCl. A further increase in the eluite concentration will cause the signal to increase again and at sufficiently high concentration the signal may even be above the second detector background which is a clear indication of overload. In an intermediate concentration regime, second detector output reversal may occur at the very top of the eluite peak, albeit the output never exceeds second detector background. This behavior is expected also of moderately weak acids such as most carboxylic acids.

Example 5 (Single Conversion)

In Figure 9a, the theoretical expectations for a sample containing propionate at three different concentrations (indicated concentrations are those at the peakmaximum) with a background NaOH concentration of 100 μM are indicated. A tailing Gaussian eluite concentration profile, was assumed and this is exactly reproduced (except in inverted form) by the response at the lower injected propionate concentration. The equivalent conductance for propionate was assumed to be 35 S cm² eq^"1. At eluite peak concentrations higher than that of the background [NaOH] , signal reversal occurs at the peak and it has the appearance of a split peak. Figure 9b shows the experimental observations, obtained with the experimental system of Example 3. Injected concentrations are indicated here. Once an order of magnitude dilution arising from the chromatographic process is taken into account, the actual concentrations in Figures 9a and 9b are quite comparable. Except for the experimental pack being substantially more skewed, qualitatively the experimental data closely mimics the theoretical expectations.

Example 6 (Single Conversion)

Similarly to Example 4, Figures 9c and 9d show simulated and experimentally observed responses for a very weak acid anion, borate. In this case the free acid is so poorly ionized that peak reversal does not actually occur — a broad, seemingly flat topped peak is predicted under overload conditions (the mobility of borate is assumed to be 35 μS cm² eq-¹) and the same is experimentally observed. If the second detector output is high and the response peak appears split or unusually broad, it is therefore necessary to check for overload conditions by dilution or reinjection of the sample or to increase the background NaOH concentration by increasing the CCG current before sample reinjection. The latter procedure is often faster because the CCG/MNG responds very quickly, a new stable baseline is established in a time scale of seconds.

Example 7 (Dual Conversion)

Dual-membrane ion-exchange device was fabricated by insertingaradiation-graftedpoly(ethylvinyl-acetate)- based anion-exchange membrane tube (Dasgupta, P.K., Ion Chromatography; Tarter, J.G., Eds.; Marcel-Dekker, New York, 1987, p.220-224) (CFS-1 refill fiber, Dionex Corp., Sunnyvale, CA) inside a Nafion^® tube (type 811X, Perma-Pure Products, Toms River, NJ) . Referring to Figure 11, the Nafion^® tube 120 was swelled in hot ethanol and the anion exchange membrane tube 122 was inserted within it in the swelled condition. Polyether ether ketone (PEEK) tubing (1.5-mm o.d., 1.0-mm i.d., Upchurch Scientific, Oak Harbor, WA) segments 124 were inserted at either end of tube 120 to secure leak-free connections. The assembly was connected to a 10-32 threaded PEEK union 126 (Dionex) with a male fitting 128 and ferrule 130. The union was converted into a tee by drilling a hole into the central partition and providing it with 1-72 threads 132 to which approximately threaded PEEK tubing 134 could be directly connected (Morris, K. Dasgupta P.K. LC-GC 1992, 10, 149). A polypropylene jacket tube 136 was connected to the fitting 138 by hot- melt adhesive and provided within inlet/outlet aperture 140. The end of the tubing 122 protruding through union 138 is connected by a Teflon^® tubing 142, acting as a sleeve, a syringe needle tubing segment 144 acting as an insert and a male nut and ferrule. The electrolyte containing the replacement anion is pumped through 142, and the effluent from the suppressed detector is brought into the convertor through tubing 134. The electrolyte containing the replacement cation flows through tubing 140. The active length of the convertor was 43 cm.

The chromatographic pump was Beckman 110A, followed by a 4.6 x 250 mm column packed with unfunctionalized poly(styrenedivinylbenzene) particles (Hamilton Co., Reno, NV) functioning as a pulse dampener. A flow rate of 1 mL/minwas usedthroughout. An electropneumatically driven dual-stack slidervalve (Dionex Corp. , Sunnyvale, CA) equipped with a 25 μL loop was used for sample injection. Separations were carried out on a Dionex IonPac^® AS5A-5μ 100- X 4.6 mm column using an NaOH eluent. The suppressor used was a filament-filled helical tubular Nafion^® device (400 μm i.d. ca. 20 mM dodecylbenzenesulfonic acid solution (Bio-Soft S-100, Stepan Chemical Co. , North field, IL) was used as regenerant. After the suppressor, one Model 213 conductivity detector (Wescan Instruments, Santa Clara, CA) served as the suppressed signal detector followed by the convertor and then by a second identical detector for measuring the converted signal. In the convertor, except as stated, a 10 mL LiF + 1 mM NH₄F-HF and a 10 mM LiF + 2 mM LiOH solution were respectively used as the anion- and cation-exchange electrolytes. Both liquids flowed in the same direction, countercurrent to the principal flowstream of interest, at flow rates of 1-2 mL/min.

Sodium hydroxide eluent solutions were prepared from 50% stock solution (Fisher Scientific) . To prevent C0₂ intrusion, a soda-lime trap was installed. Analyte solutions were made from the corresponding alkali-metal salts or occasionally from the corresponding acids. All reagents were of reagent grade. Deionized water (specific resistance > 17 MΩ-cm) was used throughout for the preparation of eluent and sample solutions.

Some overall conclusions are as follows. The described approach is easily practiced. With the advent of relatively inexpensive personal computers (PCs) with significant computing power and the availability of accessory boards permitting time-multiplexing input/output analog signals, dual channel bipolar pulse conductometric detection techniques can easily be practiced on a single PC without further detector electronics. The PC is able to acquire the resulting data and process it, and the PC can provide all the electronics necessary for the CCG. With such an implementation, the present methods can provide an uniquely powerful combination of single column and suppressed IC that provides information beyond the sum total of that obtained with either approach.

Claims

WHAT IS CLAIMED IS:

1. Apparatus for analysis of a plurality of analyte ions in a sample solution, each species being of a common charge, said charge being one of positive or negative, said apparatus comprising

(a) separating means including separating medium for separating the analyte ions in the presence of an eluent comprising an electrolyte,

(b) suppressor means in fluid communication with the effluent eluting from the separating means for converting the electrolyte of the effluent to weakly ionized form and the analyte ions to acid or base form,

(c) first detection means for detecting the conductivity of the suppressor effluent from said suppressor means and for generating a first signal,

(d) salt conversion means downstream of and in fluid communication with said first detection means for converting the analyte ions in acid or base form into a salt form, and (e) second detection means downstream of and in fluid communication with said salt conversion means for detecting the conductivity of effluent from said salt conversion means and for generating a second signal.

2. The apparatus of Claim 1 in which said salt conversion means comprises at least one ion source channel, a suppressor effluent flow channel, and at least one permselective ion exchange membrane partitioning said one ion source channel and suppressor effluent flow channel, said suppressor effluent flow channel being in fluid communication with the effluent from said suppressor means.

3. The apparatus of Claim 2 further comprising means for applying an electrical potential between said one ion source channel and suppressor effluent flow channel.

4. The apparatus of Claim 2 in which said salt conversion means further comprises a second ion source channel and a second permselective ion exchange membrane of opposite charge to said first membrane and partitioning said second ion source channel from said suppressor effluent flow channel.

5. The apparatus of Claim 1 further comprising means for receiving said first and second signals as input signals thereto and for providing an output signal representing a defined relationship between said input signals.

6. The apparatus of Claim 1 in which said salt conversion means comprises at least one ion source channel, a suppressor effluent flow channel, and at least one porous partition between said one ion source channel and suppressor effluent flow channel, said porous partition including pores of sufficient size to pass a base for negatively charged analyte ions or an acid for positively charged analyte ions, said apparatus further comprising means for applying an electrical potential between said one ion source channel and suppressor effluent flow channel, said latter channel being in fluid communication with the effluent from said suppressor means.

7. The apparatus of Claim 1 in which said salt conversion means comprises at least one ion source channel, a suppressor effluent flow channel, and at least one porous partition between said one ion source channel and suppressor effluent flow channel, said porous partition including pores of sufficient size to pass a base for negatively charged analyte ions or an acid for positively charged analyte ions, said apparatus including pumping means for supplying suppressor effluent to said suppressor effluent flow channel and for supplying said acid or base to said one ion source channel so that the pressure in said ion source channel is higher than the pressure in said suppressor effluent flow channel, whereby the flow of liquid between the two channels is in the direction of the suppression effluent flow channel.

8. The apparatus of Claim 1 in which said salt conversion means comprises sequential first and second convertors, said first convertor being capable of converting the analyte ions in acid or base form to a first salt by reaction with first salt-forming ions of opposite charge to said analyte ions by an ion exchange reaction, and said second convertor being capable of converting said first salt to a second salt by an ion exchange reaction in which the analyte ions in said first salt are converted to said second salt by reaction with a second salt-forming ion of the same charge as said analyte ions in an ion exchange process.

9. The apparatus of Claim l in which said salt conversion means comprises sequential first and second convertors, said first convertor being capable of converting the analyte ions in acid or base form to a converted acid or base by ion exchange with a single, common converting ion of the same charge as said analyte ion, and said second convertor being capable of converting said converted acid or base to salt form by an ion exchange reaction with a salt-forming ion of opposite charge to said analyte ions.

10. The apparatus of Claims 8 or 9 in which said first convertor comprises a first ion source channel, a first suppressor effluent flow channel, and a permselective ion exchange membrane partitioning said first ion source channel and said first suppressor effluent flow channel, said one membrane including exchangeable ions of the same charge as said analyte ions, said suppressor effluent flow channel being in fluid communication with the effluent from said first detection means.

11. The apparatus of Claim 10 in which said second convertor comprises a second ion source channel, a second suppressor effluent flow channel, and a second permselective ion exchange membrane of opposite charge to said first membrane and partitioning said second ion source channel from said second suppressor effluent flow channel.

12. The apparatus of Claim 8 in which said first convertor comprises a first salt-forming ion source channel, a first suppressor effluent flow channel, and a first permselective ion exchangemembrane partitioning said first ion source channel and first suppressor effluent flow channel, said one membrane including exchangeable ions of the same charge as first salt- forming ions of opposite charge to said analyte ions in said first ion source channel and being resistant to transmembrane passage of said analyte ions, said suppressor effluent flow channel being in fluid communication with the effluent from said first detection means.

13. The apparatus of Claim 12 in which said second convertor comprises a second salt-forming ion source channel for a second salt-forming ion of the same charge as said analyte ions, a second suppressor effluent flow channel and a second permselective ion exchange membrane of opposite charge to said first membrane and partitioning said second ion source channel from said second suppressor effluent flow channel, wherein second salt-forming ion converts said first salt to a second salt of said first and second salt-forming ions.

14. The apparatus of Claim 8 in which said first and second convertors comprise sequential first and second ion exchange medium beds of opposite charge.

15. The apparatus of Claim 1 in which said salt conversion means comprises a bed including ion exchange medium with exchangeable ions of positive and negative charge.

16. A method for analysis of a plurality of analyte ions in a sample solution, each analyte ion being of a common charge, said charge being one of positive or negative, said method comprising:

(a) eluting said sample solution in the presence of an eluent comprising an electrolyte through separating medium effective to separate the analyte ions,

(b) flowing the effluent from the separating medium through a suppressor in which the electrolyte is converted to weakly ionized form and the analyte ions are converted to acid or base form, (c) detecting the conductivity of the effluent from the suppressor to produce a first signal, (d) thereafter converting the analyte ions in the suppressor effluent into a first salt by reaction with first salt-forming ions of opposite charge, and

(e) detecting the conductivity of the effluent from the salt conversion zone to produce a second signal.

17. The method of Claim 16 in which step (d) includes the steps of flowing a first solution, containing an acid or base of said first salt-forming ions, through at least a first salt-forming ion source channel separated by at least one permselective ion exchange membrane from a suppressor effluent flow channel in a first convertor zone, said one membrane including exchangeable ions of the same charge as said first salt- forming ions and being resistant to transmembrane passage of ions of the opposite charge, flowing the suppressor effluent through said suppressor effluent flow channel, so that said first salt-forming ions pass from said one ion source channel to said suppressor effluent flow channel to form a salt with said analyte ions in an ion exchange reaction.

18. The method of Claim 16 in which said first convertor zone of step (d) further comprises a second salt-forming ion source channel for a second salt- forming ion of the same charge as said analyte ions and a second permselective ion exchange membrane of opposite charge to said first membrane and partitioning said second ion source channel from said suppressor effluent flow channel, said method further comprising flowing a second solution, containing second salt-forming ions of the same charge as said analyte ions, through said second ion source channel so that said second salt- forming ion converts said first salt to a second salt of said first and second salt-forming ions.

19. The method of Claim 18 in which said salt-forming ions are positively charged and selected from the group consisting of alkali metal ions, alkaline earth ions and ammonium ions.

20. The method of Claim 18 in which step (d) is performed by passing said suppressor effluent through ion exchange medium having exchangeable ions comprising said first salt-forming ions.

21. The method of Claim 16 further comprising receiving said first and second signals as input signals and providing an output signal representing a define relationship between said input signals.

22. The method of Claim 16 in which said eluent is in gradient form.

23. The method of Claim 16 in which step (d) further comprises flowing said suppressor effluent through a first convertor zone in which the analyte ions in acid or base form are converted to a first salt by reaction with first salt-forming ions of opposite charge to said analyte ions in an ion exchange reaction, and then to a second convertor zone in which said first salt is converted to a second salt by an ion exchange reaction in which said first salt is converted to said second salt by reaction with a second salt-forming ion of the same charge as said analyte ions.

24. The method of Claim 23 in which step (d) further comprises steps of flowing a first solution, containing an acid or base having first salt-forming ions of opposite charge to said analyte ions, through at least a first salt-forming ion source channel separated by at least one permselective ion exchange membrane from a suppressor effluent flow channel in said irst convertor zone, said one membrane including exchangeable ions of the same charge as said first salt-forming ions and being resistant to transmembrane passage of ions of the opposite charge, flowing the suppressor effluent through said suppressor effluent flow channel, so that said first salt-forming ions pass from said one ion source channel to said suppressor effluent flow channel to form a salt with said analyte ions.

25. The method of Claim 24 further comprising passing effluent from said first convertor zone into a second suppressor effluent flow channel of a second convertor zone comprising a second salt-forming source channel for a second salt-forming ion of the same charge as said analyte ions and a second permselective ion exchange membrane of opposite charge to said first membrane and partitioning said second ion source channel from said second suppressor effluent flow channel, and flowing a second salt-forming ion source of the same charge as said analyte ions through said second salt-forming ion source channel to convert said first salt to a second salt of said first and second salt-forming ions.

26. The method of Claim 23 in which said first and second salt convertor zones comprise first and second ion exchange resin beds of opposite charges.

27. The method of Claim 16 in which step (d) further comprises flowing said suppressor effluent through a first convertor zone in which the analyte ions in acid or base form are converted to a corresponding acid or base form by reaction with a first converting single ion of the same charge as said analyte ions in an ion exchange reaction, and then to a second convertor zone in which said corresponding acid or base is converted to a converted salt by an ion exchange reaction in which said corresponding acid or base is converted to a salt by reaction with said first salt-forming ion of opposite charge to said analyte ions.

28. The method of Claim 27 in which step (d) includes the steps of flowing a first solution, containing an acid or base having first converting single ions of the same charge as said analyte ions, through at least a first converting ion source channel separated by at least one permselective ion exchange membrane from a suppressor effluent flow channel in said first conversion zone said onemembrane including exchangeable ions of the same charge as said first converting single ions and being resistant to transmembrane passage of ions of the opposite charge, flowing the suppressor effluent through said suppressor effluent flow channel, so that said first converting single ions pass from said first converting source channel to said suppressor effluent flow channel to form said corresponding acid or base and passing effluent from said first convertor zone into a second suppressor effluent flow channel of a second convertor zone comprising a salt-forming source channel for an ion of opposite charge to said analyte ions and a second permselective ion exchange membrane of opposite charge to said first membrane and partitioning said salt-forming ion source channel from said second suppressor effluent flow channel, and flowing salt-forming ion source of opposite charge to said analyte ions through said salt-forming ion source channel to convert said corresponding acid or base to a second salt of said first and second salt-forming ions.

29. The method of Claim 27 in which said first and second convertors comprise sequential first and second ion exchange medium beds of opposite charge series.

30. The method of Claim 16 in which step (d) is performed by flowing said suppressor effluent through a bed including ion exchange medium with exchangeable ions of positive and negative charge.