Electrochemically regenerated ion neutralization and concentration devices and systems

A system and method for electrochemically regenerated ion neutralization and concentration is disclosed. In one aspect of the invention, a system is provided comprising a HPLC column pump, a concentrator column, an analytical column, a suppressor, a detector, a mixed bed deionizing resin, a sample injector, and a neutralization cartridge.

FIELD OF THE INVENTION 
This invention concerns the field of ion chromatography (IC) and, more 
particularly, the field of high pressure liquid chromatography (HPLC). 
BACKGROUND OF THE INVENTION 
The determination of inorganic constituents in concentrated acids and bases 
is important in a variety of chemical and other processes. However, when 
using ion chromatography (IC) it is often difficult to detect trace 
amounts of anions in concentrated bases or trace amounts of cations in 
concentrated acids. In other words, anion samples that are highly basic 
(high concentration of hydroxide) or cation samples that are highly acidic 
(high concentration of hydronium ions) are difficult to analyze by IC 
because the high concentration of hydroxide or hydronium ions mask the ion 
peaks (either anion or cation, respectively) of interest. 
In order to address this problem, one method used in the art is to pretreat 
the sample using an ion resin or ion exchange bed to remove the 
interfering ions (e.g., the hydroxide ions in anion analysis and hydronium 
ions in cation analysis) from the sample. Accordingly, the interfering 
hydroxide orhydronium ions may be removed by passing the sample through an 
ion-exchange bed or ion exchange resin which removes the interfering ions 
according to the following neutralization reaction: 
For anion analysis, the sample is passed through a cation exchange resin in 
the hydronium form (X=sample anion, M=sample/hydroxide countercation): 
MOH(sample)+Resin-H.fwdarw.Resin-M+H2O 
Excess sample hydroxide is neutralized to water. Sample anions are 
converted to their corresponding acids: 
MX(sample)+Resin-H.fwdarw.Resin-M+HX 
For cation analysis, the sample is passed through an anion-exchange resin 
in the hydroxide form (X=sample/acid counteranion, M=sample cation). 
HX(sample)+Resin-OH.fwdarw.Resin-X+H2O 
Excess sample acid is neutralized to water. Sample cations are converted to 
their corresponding hydroxide salts: 
MX(sample)+Resin-OH.fwdarw.Resin-X+MOH 
One prior art method for accomplishing the above described neutralization 
of interfering ions is passing the sample through a disposable 
pre-treatment, ion-exchange bed before flowing the sample ions to the 
analytical column. One such disposable ion-exchange bed known in the art 
is sold by the assignee of this application, ALLTECH ASSOCIATES, Inc. This 
pre-treatment neutralization column is sold by ALLTECH under the name 
ALLTECH's Maxi-Clean.TM. IC-OH or IC-H cartridges. These ALLTECH devices 
are solid-phase extraction devices used to eliminate interfering ions 
(e.g. matrix interferences) from samples prior to analysis by ion 
chromatography. The foregoing ALLTECH devices, as well as the other 
similar neutralization columns or cartridges presently on the market, 
suffer from the following drawbacks: 
1) Each cartridge is normally used only once and then discarded. This can 
be expensive. 
2) Passing the samples through the cartridges is a manual, labor intensive 
process that can be difficult to automate. 
There have been attempts by others to address the problems of the 
disposable neutralization columns described above. One such method is 
disclosed by Siriraks and Stillian (Journal of Chromatography, 640 (1993) 
151-160). Sirirak et al. disclose an electrolytically regenerated 
micromembrane-based technique for removing matrix interferences and 
neutralizing samples. According to this technique, a self-regenerating 
suppressor (SRS) device, which is a suppressor for reducing background 
noise of the mobile phase after the analytical column, is also disclosed 
for use as a pre-treatment (e.g., before flowing the sample to the 
analytical column) device for neutralization of the sample. The SRS devise 
is thus disclosed as a pretreatment device for trace anion determination 
in concentrated bases and trace cation analysis in concentrated acids. 
The technique disclosed by Sirirak et al. avoids some of the prior art 
problems such as, for example, the need for disposing of the pretreatment 
cartridge after every run. The SRS device is self-regenerating. For a more 
detailed discussion of the SRS system, those skilled in the art are 
referred to the above cited Sirirak et al. article. 
Despite these improvements, the SRS device is, however, not without its 
shortcomings. The SRS device uses sensitive membranes. These membranes 
have inherently low ion-exchange capacity, compared to ion-exchange resin 
beds, and require a complex recycling/monitoring scheme to completely 
neutralize strongly acidic or basic samples. Additionally, membrane-based 
suppressors are inherently fragile and are susceptible to rupturing under 
the high-pressures present ahead of the column in an IC system. 
Consequently, additional valves are required to neutralize the sample 
off-line and then insert it into the analysis stream. A separate stream of 
high-purity water is also required to feed the electrolytic micromembrane 
suppressor (the SRS) during regeneration, adding further expense and 
complication to the device. The present invention is intended to address 
the foregoing problems in the art relating to sample neutralization. 
Another pre-treatment method known in the art is pre-concentrating 
relatively dilute samples for better detection and quantification. Many 
samples contain trace amounts of anions and cations at levels too low to 
detect by direct injection into an IC system, even where interfering ions 
(hydroxide and hydronium) are not present. In these situations, samples 
are normally pumped onto a short ion-exchange column (the 
pre-concentration column), which traps the sample ions of interest while 
the balance of the sample is flowed to waste. The trapped sample ions are 
then eluted from the pre-concentration column in a much smaller volume 
and, thus, at a correspondingly much greater concentration than in the 
original sample. The highly concentrated sample is then flowed to an 
analytical column for separation and then to a detector for detection and 
quantification. 
In prior art pre-concentration systems, the pre-concentration column is 
usually installed onto a six-port sample injection valve and the sample is 
delivered to the pre-concentration column by a separate pump. Thus, this 
system requires an additional pump in the IC system and can also be 
difficult to automate. 
The present invention is also intended to address these problems as well. 
SUMMARY OF THE INVENTION 
A system for electrochemically regenerated ion neutralization for use in 
ion chromatography comprising a HPLC pump, a concentrator column, an 
analytical column, a suppressor, a detector, a mixed-bed dionizing resin, 
a sample injection valve, a sample loop, a neutralization ion exchange 
cartridge wherein the suppressor and neutralization ion exchange cartridge 
each comprises: a housing, the housing comprising an effluent flow channel 
comprising chromatography material and the effluent flow channel adapted 
to permit fluid flow therethrough; a first and second electrode positioned 
such that at least a portion of the chromatography material is disposed 
between the first and second electrodes, and the fluid flow through the 
effluent flow channel is between, and in contact with, the first and 
second electrodes; and a power source connected to the first and second 
electrodes. 
In a preferred embodiment of the system described above, the sample 
injection valve comprises a six-port valve. 
A system for electrochemically regenerated ion concentration for use in ion 
chromatography comprising a HPLC pump, a concentrator column, an 
analytical column, a suppressor, a detector, a mixed-bed dionizing resin, 
a sample injection valve, a sample loop, a neutralization ion exchange 
cartridge wherein the suppressor and neutralization ion exchange cartridge 
each comprises: a housing, the housing comprising an effluent flow channel 
comprising chromatography material and the effluent flow channel adapted 
to permit fluid flow therethrough; a first and second electrode positioned 
such that at least a portion of the chromatography material is disposed 
between the first and second electrodes, and the fluid flow through the 
effluent flow channel is between, and in contact with, the first and 
second electrodes; and a power source connected to the first and second 
electrodes. 
In yet another aspect of the invention, a method of ion chromatography by 
mobile phase neutralization and sample ion concentration is provided. 
According to this method, an acidic or basic first mobile phase comprising 
interfering ions and sample ions is provided and flowed through a 
neutralizer comprising neutralization ions selected from the group 
consisting of hydronium ions and hydroxide ions. The mobile phase is 
neutralized by ion exchange of the interfering ions with the 
neutralization ions thereby at least partially exhausting the neutralizer 
and generating a neutralizer effluent. The neutralizer effluent is then 
flowed to a concentrator comprising ion exchange resin where the sample 
ions are then retained in the concentrator. A second mobile phase is then 
flowed through the concentrator to elute the retained sample ions. The 
resulting first concentrator effluent comprising sample ions is then 
flowed to an analytical column where the sample ions are separated. The 
resulting analytical column effluent is then flowed to a suppressor for 
suppression of the mobile phase. The resulting suppressor effluent is then 
flowed to a detector for detecting the separated sample ions. Detector 
effluent is then flowed through a deionization resin comprising 
deionization ions selected from the group consisting of hydronium ions and 
hydroxide ions where the sample ions are removed from the detector 
effluent by ion exchange of the sample ions with the deionization ions. 
Electrolysis is performed on the resulting deionization resin effluent to 
generate hydrolysis ions selected from the group consisting of hydronium 
ions and hydroxide ions. The hydrolysis ions are then flowed back through 
the at least partially exhausted neutralizer to regenerate the 
neutralizer. 
Additionally, a second concentrator effluent generated by the initial step 
of concentrating the sample ions in the concentrator may be flowed to an 
at least partially exhausted suppressor where electrolysis is conducted on 
the second concentrator effluent to generate hydrolysis ions selected from 
the group consisting of hydronium ions and hydroxide ions. The hydrolysis 
ions are then flowed through the at least partially exhausted suppressor 
to regenerate it. 
Moreover, once the neutralizer is regenerated as discussed above, 
hydrolysis ions may be flowed through the regenerated neutralizer to an at 
least partially exhausted suppressor to regenerate the suppressor. 
In yet another aspect of the invention, a method of ion chromatography by 
sample ion concentration is provided. In this method a first mobile phase 
and sample ions are provided and flowed to a concentrator comprising ion 
exchange resin where the sample ions are retained in the concentrator. A 
second mobile phase and is then flowed through the concentrator to elute 
the retained sample ions. The resulting first concentrator effluent 
comprising sample ions is then flowed to an analytical column where the 
sample ions are separated. The resulting analytical column effluent is 
then flowed to a suppressor where the second mobile phase is suppressed. 
The resulting suppressor effluent is flowed to a detector where the sample 
ions are detected. The detector effluent is then flowed through a 
deionization resin comprising deionization ions selected from the group 
consisting of hydronium ions and hydroxide ions where the sample ions are 
removed from the detector effluent by ion exchange of the sample ions with 
the deionization ions. Electrolysis is subsequently conducted on the 
deionization resin effluent to generate hydrolysis ions selected from the 
group consisting of hydronium ions and hydroxide ions. These hydrolysis 
ions may then be flowed through an at least partially exhausted suppressor 
to regenerate the suppressor. 
Additionally, hydrolysis may be performed on a second concentrator effluent 
generated in the step of concentrating the sample ions in the concentrator 
to generate hydrolysis ions. These hydrolysis ions may also be used to 
regenerate an at partially exhausted suppressor.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
In co-pending application Ser. Nos. 08/609,171; 08/486,210; and 08/399,706; 
the disclosures of which are all incorporated herein by reference, 
self-regenerating columns are disclosed which are preferably adaptable for 
use in the apparatus and systems of this invention. These 
self-regenerating columns or cartridges disclosed in the co-pending 
applications are preferably packed with either cation or anion exchange 
resin and used as the neutralization column or cartridge in the 
electronically regenerated ion neutralization system of the present 
invention. These same self-regenerating columns are also used as the 
suppressor in the systems of the present invention. 
The self-regeneration columns of applicants' co-pending applications are 
equipped with, inter alia, electrodes which permit electrolysis of the 
mobile phase. The electrolysis of the mobile phase provides a source of, 
for example, hydronium or hydroxide ions, which are flowed across the 
exhausted or partially exhausted ion-exchange bed of the self-regenerating 
column. These hydronium ions or hydroxide ions, as the case may be, 
convert the exhausted ion-exchange bed or resin back to either its 
hydronium or hydroxide form thereby regenerating the ion-exchange bed or 
resin of the column. In a preferred embodiment of the invention disclosed 
in applicants' co-pending applications, the suppressed detector effluent 
(which consists of deionized water) is the mobile phase which undergoes 
the electrolysis to yield the replenishing hydronium or hydroxide ions. 
It occurred to applicants that the invention of its co-pending applications 
could be advantageously applied to the prior art problems associated with 
sample neutralization and pre-concentration outlined above. For further 
details concerning the preferred self-regeneration columns used in the 
systems and apparatus of this invention, those skilled in the art are 
encouraged to consult applicants' above-identified co-pending 
applications. 
By using the self-regeneration columns of applicants' co-pending 
applications, the present invention overcomes some of the disadvantages of 
the prior art neutralization techniques. This is accomplished by using the 
electrochemically-regenerated ion-exchange columns of applicants' 
co-pending applications to neutralize samples prior to IC analysis. By 
regenerating the ion-exchange bed between runs (or as often as necessary) 
as disclosed in applicants' co-pending applications, a single packed bed 
may be used to neutralize multiple samples, eliminating the cost of 
disposable cartridges that are typically used to process only one sample. 
An additional advantage to the system of the present invention is the 
inherently high ion-exchange capacity of ion-exchange beds. Thus, multiple 
neutralizations of samples may be accomplished without the recycling 
required with the prior art membrane-based devices. Additionally, the ion 
exchange beds of the present invention will tolerate the high 
backpressures typically encountered in HPLC and IC systems, and may be 
inserted in-line for greatly simplified operation compared to prior art 
micromembrane devices. 
The system of this invention is also capable of automation using existing 
autosamplers such as the ALLTECH 580 Autosampler, eliminating 
labor-intensive manual off-line disposable packed-bed procedures. Finally, 
the present invention advantageously uses the suppressed detector effluent 
from the IC system to push the sample through the neutralization 
ion-exchange bed and to provide flow during electrochemical regeneration 
of the neutralization column or cartridge. This eliminates the need for a 
separate source of deionized water, as required by the prior art 
micromembrane devices. 
A preferred aspect of the electrochemically regenerated ion neutralization 
system of the present invention will be described with reference to FIGS. 
1, 2 and 3. 
With reference to FIG. 1, the system preferably consists of an HPLC pump 1, 
a concentrator column 2, an analytical column 3, a suppressor 4, a 
conductivity detector 5, a mixed bed deionizing resin 6, a sample 
injection valve 7, a sample loop 8, neutralization ion exchange cartridge 
9, and 10-port valve 10. The suppressor 4 preferably comprises two 
separate columns (not shown) as discussed in applicants' copending 
applications. Further details about the suppressor 4 are disclosed in 
applicants' co-pending applications. 
Still with reference to FIG. 1, flow for sample loading is as follows. The 
detector effluent from the detector 5, which contains suppressed eluant 
and at times analytes from the previous run, is deionized by passing the 
detector effluent through mixed-bed deionizing resin 6. The effluent from 
the mixed-bed 6 (high-purity water) is flowed to a six-port manual or 
automated (autosampler) sample injection valve 7. The sample is loaded 
into a sample loop 8 in the sample injection valve 7. The mixed-bed 
effluent (high-purity water) is flowed through the sample injection valve 
7 to the valve 10, and is delivered to the suppressor 4 through cartridge 
9. At the suppressor 4, the water undergoes hydrolysis and 
electrochemically regenerates the suppressor 4 as described in applicants' 
co-pending applications. The electrolysis by-products from the 
regeneration of suppressor 4 is flowed to waste. 
Still with reference to FIG. 1, mobile phase (the eluant) from the HPLC 
pump 1 is flowed through the valve 10, through concentrator 2, to the 
analytical column 3, to suppressor 4, and detector 5. The detector 
effluent is flowed through mixed-bed 6 to yield a steady supply of 
deionized water. 
With reference to FIG. 2, for sample neutralization the mobile phase flow 
in both the sample injection valve 7 and the valve 10 is switched. The 
mixed-bed effluent (high purity water) is flowed from the mixed-bed 6 to 
the sample injection valve 7, and then flows or delivers the sample from 
sample loop 8 to valve 10. Still under the driving pressure from the 
mixed-bed effluent, the sample is flowed through the neutralization ion 
exchange cartridge 9. The cartridge preferably comprises a packed-bed 
neutralization ion-exchange resin. Here, the sample undergoes the 
previously described neutralization reactions. An anion exchange resin in 
the hydroxide form may be used for neutralization in cation analysis. A 
cation exchange resin bed in the hydronium form may be used for 
neutralization in anion analysis. The various cation and anion exchange 
resins disclosed in applicants' co-pending application are preferably 
used. 
The effluent from the neutralization ion exchange cartridge 9, which 
contains the sample ions in high-purity water, is flowed to a concentrator 
column 2. The analyte or sample ions are retained by ion-exchange resin in 
the concentrator column 2. The concentrator column 2 is preferably a very 
small (4.6 mm.times.7.5 mm) bed filled with the same packing material used 
in the analytical column 3. The preferred resins for cation or anion 
analysis are disclosed in applicants' co-pending applications. In any 
event, because the sample ions are delivered to the concentrator column 2 
by deionized water, which has little or no eluting power, the sample ions 
are retained on the concentrator column 2 without breakthrough. The mobile 
phase flow in sample injection valve 7 and valve 10 is maintained until 
all of the sample has been flowed through the neutralization bed 9 and to 
the concentrator column 2. The concentrator effluent, which is water, is 
flowed to the suppressor 4 for hydrolysis and regenerating an exhausted or 
partially exhausted suppressor column as described in applicants' 
co-pending applications. During this process, the mobile phase from HPLC 
pump 1 is flowed to the analytical column 3 through the valve 10. The 
analytical column effluent is flowed to the suppressor 4, where it is 
flowed through the on-line suppressor column in the suppressor. The sample 
ions and the suppressed mobile phase are then flowed to the detector 5 for 
sample ion detection and quantification. 
With reference to FIG. 3, for sample analysis the mobile phase flow in both 
valves 10 and 7 is switched back to the flow depicted in sample loading 
(FIG. 1). The valve 10 flows mobile phase (eluant) from the HPLC pump 1 to 
the concentrator column 2. The mobile phase elutes the sample ions from 
the concentrator column 2, and flows the sample ions to the analytical 
column 3 for separation. The separated sample ions are then flowed to 
suppressor 4, where the mobile phase is suppressed. The suppressor 4 is 
constructed as previously described in applicants' co-pending 
applications. The suppressed mobile phase then flows the sample ions to 
detector 5 for detection and quantification. 
The mobile phase from detector 5 (detector effluent), which contains sample 
ions, is then flowed to the mixed-bed deionization resin 6 where the 
sample ions are exchanged with hydronium or hydroxide ions, as the case 
may be to yield water. The mixed-bed 6 deionizing effluent (highly pure 
water) is flowed to the sample injection valve 7 and then to the valve 10. 
The neutralization ion exchange cartridge 9 is constructed like the 
self-regenerating columns disclosed in applicants' co-pending 
applications. The mobile phase (which is water at this point) is flowed to 
cartridge 9 and a power source (not disclosed) is activated to permit 
electrolysis of the mobile phase thereby electrochemically regenerating 
the exhausted or partially exhausted resin contained therein as described 
in applicants' co-pending applications. The regeneration current and 
regeneration time are adjusted to completely displace the retained sample 
counterions and purge electrolysis byproducts from the bed before the next 
sample is applied. The neutralization cartridge 9 effluent is flowed to 
suppressor 4, where it may be flowed to waste or used to regenerate an 
exhausted suppressor column in suppressor 4. During this time, the next 
sample to be loaded is flowed into the sample loop 8 of injection valve 7. 
In all flow configurations, the waste from the valve 10 is continuously fed 
into the suppressor 4 as a feed source for electrochemically regenerating 
the suppressor 4 as disclosed in applicants' co-pending applications. If 
analysis time permits, however, it is preferred to sequentially regenerate 
cartridge 9 and then suppressor 4. 
The foregoing system discussed with respect to FIGS. 1-3 can be 
reconfigured for use in electrochemically regenerated ion concentration. 
This can be accomplished by removing the neutralization ion-exchange 
cartridge 9 from the valve 10 shown in FIGS. 1-3. In this fashion, large 
volumes of dilute samples can be flowed from the sample loop 8 in the 
injection valve 7 onto the concentrator column 2 in the valve 10 without 
requiring a secondary pump. This involves a three step process, which will 
be described with reference to FIGS. 1--3. 
Sample is loaded into the system in the same fashion as previously 
described with respect to FIG. 1. 
With reference to FIG. 2, for sample concentration mobile phase flow is 
switched in sample injection valve 7 and valve 10 and mixed-bed 6 effluent 
(deionized water) is flowed to the sample injection valve 7 (preferably a 
six-port valve). The mixed-bed effluent then flows the sample from the 
sample loop 8 to the valve 10 (preferably a 10-port valve). The sample 
loop 8 preferably contains a large volume (1 mL to 100 mL) of sample to 
provide the desired preconcentration effect. Recall that in this 
embodiment there is not a neutralization ion exchange cartridge 9 
connected to valve 10. The sample is flowed through a concentrator column 
2 where sample ions are retained by ion-exchange. The concentrator column 
2 preferably is a very small (4.6 mm.times.7.5 mm) bed filled with the 
same packing materials used in the analytical column 3. The preferred 
cation and anion exchange resins are disclosed in applicants' co-pending 
applications. Because the sample ions are delivered to the concentrator 
column 2 by deionized water, which has little or no eluting power, the 
sample ions are retained on the concentrator column 2 without 
breakthrough. The mobile phase flow in injection valve 7 and valve 10 
continues until all of the sample has been delivered onto the concentrator 
2. During this process, the HPLC pump I delivers mobile phase (eluant) to 
the analytical column 3 through the valve 10 and through suppressor 4. The 
suppressed eluant is flowed through the mixed bed 6 yielding a steady 
source of deionized water. 
With reference to FIG. 3, for sample analysis mobile phase flow is switched 
in sample injection valve 7 and valve 10. The mobile phase flow through 
valve 10 is from the HPLC pump 1 to the concentrator column 2. The mobile 
phase elutes the sample ions from the concentrator column 2 and flows the 
sample ions to the analytical column 3 where the sample ions are 
separated. The mobile phase then flows the separated sample ions to 
suppressor 4 where the mobile phase is suppressed. The sample ions and the 
suppressed mobile phase is flowed to detector 5 where the sample ions are 
detected and quantified. During this time, the sample injection valve 7 is 
positioned to accept the next sample. 
During all three steps, the waste from the valve 10 (deionized water) is 
continuously fed into the suppressor 4 as a feed source for 
electrochemically regenerating the suppressor as described in applicants' 
co-pending applications. 
Many of the preferred materials for use in the present invention are 
disclosed in applicants' co-pending application. Other preferred materials 
for ion neutralization include: for anions in caustic (NaOH) 
solution--analytical column -ALLTECH's ALLSEP Anionic Column, 100.times.4 
mm; mobile phase--0.85 mM NaHCO.sub.3 : 0.9 mM Na.sub.2 CO.sub.3 ; 
flowrate--1.2 mL/min; detector--suppressed conductivity; for cations in 
HC1 analytical column--Universal Cation, 100.times.4.6 mm; mobile phase--3 
mM Methanesulfonic Acid; flowrate--1.0 mL/min; column 
temperature--35.degree. C.; detector-conductivity; for trace anions in 
silica HPLC stationary phase--column ALLSEP anionic column, 100.times.4.6 
mm; mobile phase--0.85 mM NaHCO.sub.3 : 0.9 mM Na.sub.2 CO.sub.3 ; 
flowrate 1.2 mL/min detector--suppressed conductivity; for trace cations 
in nickel plating bath (35,000 ppm boric acid)--column--Universal Cation, 
100.times.4.6; mobile phase--3 mM Methanesulfonic Acid; flowrate--1.0 
mL/min; column temperature--35.degree. C.; and detector - Conductivity. 
The various materials and apparatus described above and in applicants' 
co-pending application are available from the assignee of these 
applications, ALLTECH ASSOCIATES, INC., Deerfield, Ill. 
As those skilled in the art will recognize, the systems and methods of the 
present invention can be used in variety of modified forms and 
applications. The foregoing discussion is intended to describe certain 
preferred aspects of the present invention and should not be considered to 
limit the scope of the invention.