Patent Grant
10175211
The present application relates to a current efficient electrolytic device and method for reducing the concentration of matrix ions of opposite charge to ions to be analyzed, and specifically for use in an ion chromatography suppressor or to a pretreatment device.
According to the invention, an apparatus is provided for treating an aqueous sample stream including analyte ions. The apparatus comprises a first ion exchange barrier capable of passing only ions of opposite charge to the analyte ions; a sample stream flow channel, an ion receiving stream flow channel adjacent to the sample stream flow channel and separated therefrom by the first ion exchange barrier, stationary flow-through first ion exchange packing disposed in the sample stream flow channel of the same charge, as the first ion exchange barrier. The stationary flow-through first ion exchange packing with exchangeable ions of opposite charge to the analyte ions comprises a mixture of a first ion exchange portion with strong ionizable groups and a second ion exchange portion with weak ionizable groups, both portions having ionizable groups of the same charge, positive or negative. Also, it includes first and second electrodes in electrical communication with the sample stream flow channel and the ion receiving stream flow channel, respectively. Also, a method is provided for using the apparatus.
The suppressor or pretreatment device and method of the present invention are improvements over that of issued U.S. Pat. No. 6,077,434 (hereinafter the '434 patent), and of the ones described in US 2014/0134050 A1 (hereinafter the '050 publication). In general, the invention uses the apparatus and method of the '434 patent except where otherwise described herein. The most significant difference relates to the packing in the sample stream flow channel. Thus, the description of the suppressor and pretreatment device, and definitions set forth in the '434 patent, at column 4, line 11 through column 12, line 44, particularly,
Electrolytic suppressors such as disclosed in the '434 patent are in widespread use in the field of ion chromatography as they confer significant ease of use to the user and, in the recycle mode, do not require any additional reagents for operation. In operation the user inputs a current for a given eluent concentration. The current needed to suppress a given eluent at 100% current efficiency can be easily calculated based on Faraday's equation.
where
By way of example, for suppressing an eluent comprising of 20 mM potassium hydroxide eluent the above equation calculates the required current to be approximately 32 mA. As the current efficiency of a suppressor device decreases the current required for suppression increases. It is known that if the current applied increases for a given suppressor the noise increases and the wattage increases. Maintaining a high current efficiency is therefore important as this ensures that the suppressor draws the current required for suppression.
It has been discovered that the use of current efficient devices for constant voltage operation as disclosed in the '434 patent has a limitation in that knowledge of the optimal voltage setting is needed for proper chromatographic operation. When the set voltage deviates from the optimum voltage, the net effect is loss of peak efficiency and peak asymmetry. Such devices preferably operate only at the predetermined optimum voltage and the optimum voltage can only be obtained from experimentation by running the experiment under a variety of voltages and decipher the optimum voltage. This approach is cumbersome and adds significant time to the method development aspect. Further suppressor to suppressor variation and system to system variation is expected to make the method less reliable. The present invention solves these issues.
The device of the present invention is less sensitive to applied voltage variations with peak efficiency and peak shapes preserved compared to the '434 patent. The suppressor performs reliably under a variety of eluent and system conditions. Constant current operation is feasible according to the present invention. The end user can provide input on the applied current. For example, when using an electrolytic eluent generation, the eluent strength is known and this input can be used to calculate the applied current required for the suppressor of the present invention. In an embodiment, the substantially constant voltage may vary by +/−10%, +/−5%, +/−4%, +/−3%, +/−2%, +/−1%, +/−0.1%, or less than the absolute value of +/−0.1% of the set voltage.
One embodiment of the present invention, based on the suppressor described in the '434 patent, is a single ion exchange barrier (preferably an ion exchange membrane) suppressor-type device. The present description generally will use the terms “ion exchange membrane” and “ion exchange barrier” interchangeably. The apparatus can be used for ion chromatographic or pretreatment of a liquid sample stream including analyte ions as described in the '434 patent. According to the invention, apparatus is provided for treating an aqueous sample stream including analyte ions. The apparatus comprises (a) an ion exchange barrier capable of passing only ions of opposite charge to the analyte ions; (b) a sample stream flow channel, (c) an ion receiving stream flow channel adjacent to the sample stream flow channel and separated therefrom by the first ion exchange barrier, and (d) stationary flow-through first ion exchange packing disposed in the sample flow channel of the same charge as the first ion exchange barrier. The packing has exchangeable ions of opposite charge to the analyte ions and comprises a mixture of a first ion exchange portion with strong ionizable groups and a second ion exchange portion with weak ionizable groups, both portions having ionizable groups of the same charge, positive or negative. Also, it includes first and second electrodes in electrical communication with the sample stream flow channel and the ion receiving flow channel, respectively. Also, a method for using the apparatus is also provided.
In a preferred embodiment, the sample stream flow channel ion exchange packing comprises a bed of ion exchange particles comprising the first and second ion exchange portions. The ion exchange particles in the sample stream flow channel can also be referred to as a stationary flow-through first ion exchange packing.
The least expensive way to make such an ion exchange bed is to pre-mix ion exchange particles (e.g., ion exchange resin) in an intimate mixture and then to pack the mixed particle bed into the sample stream flow channel. It is possible to provide a mixture of strong and weak ionizable groups (ion exchange functionalities) in the packing via chemical synthesis or grafting approaches and comprising an ion exchange screen or an ion exchange monolith, but it would be far more expensive and complicated to do so. The present description will refer to the preferred mixed ion exchange particle bed.
As used herein, the terms “strong ionizable groups” and “weak ionizable groups” are defined to have the same meaning as ascribed to them by one of ordinary skill in the chromatography field. Typically, the strong ionizable groups for a cation exchanger are strong acids and for an anion exchanger are strong bases. Typically, the weak ionizable groups for a cation exchanger are weak acids and for an anion exchanger are weak bases. The first ion exchange portion typically comprises at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 97% by weight of the mixture. The second ion exchange portion typically comprises at least 3% and less than 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, or 5% by weight of the mixture. Suitable strong ionizable groups are known in the chromatography field. Dowex 50WX8 and Amberlite IR 122 are commonly used strong acid cation exchange resins. For use as a cation exchanger, they include ion exchange particles in the sulfonated, methylsulfonated, or sulfopropyl form, preferably in the sulfonated form. Chelex-100 and Bio-Rex 70, and Amberlite IRC-76 resins are commonly used weak acid cation exchange resins. For cation exchange, suitable weak ionizable groups are in the carboxylated, chlorocarboxylate, or phosphonate form, preferably in the carboxylated form.
For use as an anion exchanger, suitable strong and weak ionizable groups are also known. Strong ionizable groups include quarternary amines which could be preferably be trialkyl amine based or dialkyl 2-hydroxy ethyl ammonium based. AG 1-X8 and AG 2-X8 are example of this type of resins from Biorad laboratories. Weak ionizable groups are tertiary amine-based or secondary amine based groups. AG 3-X4 and AG 4-X4 are 4% crosslinked resin with a tertiary amine functional group from Biorad Laboratories. Diethylaminoethyl is an example of a weak base ionizable group. More information can be found at http://www.bio-rad.com/en-us/category/analytical-grade-ion-exchange-resins.
In a preferred embodiment, the ion receiving flow channel is packed with strong ionizable groups ion exchange medium, such as of the type described in the '434 patent. Such packing has the same charge as its adjacent ion exchange membrane and preferably is an ion exchange screen but can be other packing such as a packed bed of ion exchange particles or an ion exchange monolith.
Also, the invention is applicable to a sandwich-type suppressor device of the type described in the '434 patent with a second ion exchange membrane between the sample stream flow channel and an ion source flow channel, and packing in the ion source flow channel of the same charge and type used in the ion receiving flow channel.
A more recent suppressor device is described in the '050 publication.
Referring back to
The invention is further applicable to a capillary suppressor-type device such as described in U.S. Pat. Nos. 8,415,168 and 8,216,515, using the packing of the present invention in the sample stream flow channel.
In the present invention, a mixed ion exchange medium having strong ionizable ions and weak ionizable ions improves the current efficiency of the device. The following is a theoretical discussion of an anion analysis system including the weak ionizable group carboxylate form and the strong ionizable group sulfonate form of the resin particle, e.g. mixture packed in the sample stream flow channel of an anion suppressor as per the present invention. For anion analysis, a carboxylate form resin in the hydronium form is sufficiently resistive in the hydronium form to prevent easy transport of hydronium ions. The carboxylate form of the resin in hydronium form is a neutral form of the carboxylic acid molecule, and therefore is not electrically conductive and inhibits transport of hydronium ion across the resin in an electric field. In contrast to the hydronium form with the dissociated cation form such as the sodium form transport of the sodium ion is relatively facile in the carboxylate form resin.
Because the sulfonated form of the resin is strongly ionized, the transport of the ions in an electric field is independent of the form of the resin and both hydronium and the sodium form are transported freely. Since hydronium ion has a five fold higher electrical mobility than sodium ion, a fully ionized resin is extremely conductive in the hydronium ion form. This leads to poor current efficiency, particularly in the sample stream channels of the prior art which are packed entirely with the sulfonated form of the resin. Similarly packing the sample stream flow channels with the carboxylate form of the resin alone will inhibit transport of the hydronium at the outlet. Although this effect may lead to improved current efficiency due to poor current carrying ability in the outlet zone of the sample stream flow channel, the analyte peaks generally are distorted in this zone. Further, since the carboxylate form of the resin is highly resistive the voltage requirements of the device to generate the required current for suppression become prohibitive. In other words, the device has high electrical resistance.
By mixing the weak ionizable group (carboxylate) particles (e.g., ion exchange resin particles) with the strong ionizable group (e.g., sulfonated) ion exchange resin particles as per the present invention both resistive and conductive regions are created within the sample stream flow channel. As per the present invention the resistive zones preserve the current efficiency of the device by slowing down the transport of hydronium ions. By slowing the hydronium ion, the overall transport of hydronium is inhibited which is believed to achieve current efficiency in the suppressor of the present invention. Further, since there are conductive sections in the sample stream flow channel, analyte peaks after suppression are not distorted. Another benefit is the relatively low voltage required for the device operation during suppression since there is a conductive section in the outlet of the device.
Thus the benefit of having strong ionizable group (e.g., strong acid sulfonated) form resin is the relatively high conductivity which allows for some transport of ions particularly when the voltage is far from optimal. Under these conditions there is minimal or no net distortion of the analyte zones and excellent peak shapes are achieved by the device of the present invention.
The current efficient devices of the present invention produce improved current efficiency performance and peak shape performance.
According to the present invention it is not necessary to operate close to an optimum voltage. However, the device of the present invention could be calibrated by determining a voltage that would facilitate suppression of a maximum eluent concentration. For example, for anion analysis with eluent generation systems the device voltage would be determined that would facilitate the suppression of 100 mM KOH. Now this voltage would be sufficient to suppress any concentration between 0 and 100 mM KOH. Thus by predetermining the voltage to suppress the maximum concentration the device to device variation is minimized and there is no need to pursue any other experimentation.
The device of the present invention has at least the following advantages over the prior art suppressor devices such as disclosed in the '434 patent:
a) Current efficiency is achieved in the devices of the present invention by mixing fully ionized materials with partially ionized materials. Operation at a current efficient regime has benefits of low wattage and lower leachate levels that translate into a low noise performance. With gradients, the device self-adjusts to the influent concentration and is able to provide noise free operation.
b) The device is less sensitive to voltage changes and peak shape and efficiencies are preserved. in contrast the suppressors of the prior art operate at a relatively narrow regime and do not provide the flexibility required for analysis. The insensitivity to the applied voltage is feasible due to the conductive pathways in the present invention.
c) The device can operate with one applied voltage thereby conferring ease of use to the user. Since the device is not sensitive to the applied voltage application, one voltage for a given application is feasible. In contrast, optimization typically is needed for the current efficient devices of the prior art since the peak shape is non optimal as one deviates further from the current efficient voltage. The reason for this stems from not having sufficient current carrying ability in the prior art devices. In contrast due to the combination of fully functionalized (with strong ionizable groups) ion exchange particles and weakly dissociated (weak ionizable groups) ion exchange particles, there is a pathway for current to be transported in the present design which preserves the peak shapes.
d) Constant current conditions also are feasible in the devices of the present invention. The device has conductive elements in the design that allows for transport of excess current if required. In suppressors of the prior art that are current inefficient, such transport would result in poor performance. In current efficient devices of the prior art operation under constant current is feasible if the current is fine tuned to the influent equivalents of the eluent. This approach however is cumbersome. In contrast due to the conductive elements in the present design the devices of the present invention are more resilient to current changes.
As set forth above, the apparatus and method of the present invention is applicable to the following types of systems disclosed in the '434 patent:
(1) Use in combination with apparatus for performing ion chromatography. The apparatus further comprises a chromatographic separator in fluid combination with the sample stream flow channel; and a detector for the analyte ions in fluid communication with the outlet of the sample stream flow channel,
(2) Use of the apparatus for pretreatment of a sample stream and in combination with chromatography apparatus. The apparatus further comprises a chromatographic separator having an inlet and an outlet. The chromatographic separator inlet is in fluid communication with the sample stream flow channel. A detector is provided for the analyte in fluid communication with the outlet of the chromatographic separator,
(3) The apparatus further comprising a second ion exchange barrier on the opposite side of the sample stream flow channel from the ion exchange barrier and of the same charge, positive or negative. An ion source channel is provided adjacent the second ion exchange barrier.
(4) A method comprising flowing the sample stream through the sample stream flow channel and out an outlet thereof; and simultaneously flowing an aqueous ion receiving stream through the ion receiving flow channel separated therefrom by an ion exchange barrier capable of passing only ions of opposite charge to the analyte ions, while passing a current between the sample stream flow channel and the ion receiving flow channel. The same packing described above is disposed in the sample stream flow channel of the same charge as the ion exchange barrier, and
In order to illustrate the present invention, the following non-limiting examples of its practice are provided.
A 2 mm Thermo Scientific™ ASRS™ suppressor sold by Thermo Fisher Scientific was fitted with a neutral screen as described in the '434 patent. The device was nearly 100% current efficient. The device was used as a suppressor by applying various constant voltages across the device. A prototype IonPac™ AS18 column 2×250 mm was used in this work with a 32 mM KOH eluent. The flow rate was 0.25 ml/min and the injection loop size was 5 μL. A sample comprising of five standard anions such as fluoride (peak 1, 2 mg/L), chloride (peak 2, 3 mg/L), sulfate (peak 3, 15 mg/L), nitrate (peak 4, 10 mg/L) and phosphate (peak 5, 15 mg/L) was analyzed. The suppressor was operated with a DC power supply under constant voltage conditions of 3.5 volt, 4.0 volt and 4.5 volt. The resulting chromatograms are shown in
The early elutor fluoride is significantly impacted by the applied voltage and the efficiency drop from 4.0 to 5.0 volt is about 25%. Chloride also showed a 8% decline.
The peak asymmetry showed an increasing trend with voltage suggesting that the peak shape was getting worse with the increasing applied voltage using a current efficient device. The outlet portion of this prior art suppressor device does not have sufficient current carrying ability and the peak shapes are therefore affected in this zone when the voltage is increased.
A Thermo ScientificTM AERS 2 mm suppressor of the present invention was assembled (available from Thermo Fisher Scientific) as generally described in the U.S. Pre-Grant Publication 2014/0134050A1. However, in this device, the eluent channel of the device was packed with cation exchange resin with a composition comprising of 90% by weight of a sulfonated cation exchange resin and 10% of a weak carboxylated cation exchange resin. The device was tested using AS 18 chemistry under similar conditions as to Example 1.
The results shown in
The peak asymmetry also was significantly better with the device of the present invention than the prior art devices. These results are possible with the current device due to the presence of conductive pathways at the outlet of the device. Current efficiency however is maintained due to the weakly dissociated regions in the current design.
A 4 mm Thermo Scientific™ AERS suppressor (sold by Thermo Fisher Scientific) was packed with a composition comprising of 80% strong sulfonated resin and 20% weak carboxylated resin. The device of Example 2 was tested as a suppressor using an IonPac™ AS15 column 4×250 mm and with an eluent comprising of 38 mM KOH at a flow rate of 1.2 mL/min The injection loop was 25 μL. A sample comprising of seven anion standards with fluoride at 2 mg/L (peak 1), chloride at 10 mg/L (peak 2), carbonate (not quantitated, peak 3), nitrite at 10 mg/L I (peak 4), sulfate at 10 mg/L (peak 5), bromide at 10 mg/L (peak 6), nitrate at 10 mg/L (peak 7) and phosphate at 20 mg/L (peak 8) were evaluated in this study. A constant voltage of 3.5 V, 4.0 V and 4.5 V was used in this study.
A relatively smaller variation in peak efficiency was inferred for fluoride based on a 10% variation. The chloride efficiency was changed by 4%. These change values are significantly smaller than what was observed for the device of the prior art which typically showed efficiency losses of greater than 20%. Further operation near the current efficiency level is needed for the prior art devices in order to obtain the best peak shape and peak efficiency performance. These constraints are absent in the present invention due to the greater flexibility of the present design.
The peak asymmetry numbers showed a relatively small change over the applied voltage range indicating excellent performance of the suppressor device of the present invention. These results further demonstrate the utility of the resin composition of the present invention.
The Thermo Scientific™ AERS suppressor from Example 3 was also evaluated with a 4 mm IonPac™ AS19 chemistry (4×250 mm) using a 20 mM KOH eluent at 1 ml/min flow rate. An injection loop of 25 μL was used in this work. A sample comprising of anion standards comprising of fluoride (peak 1, 3 mg/L), chlorite (peak 2, not quantified), bromate (peak 3, 20 mg/L), chloride (peak 4, 6 mg/L), nitrite (peak 5, 15 mg/L), chlorate (peak 6, 25 mg/L), bromide (peak 7, 25 mg/L, nitrate (peak 8, 25 carbonate (peak 9, not quantified) and sulfate (peak 10, 30 trig/L) was used in this work. The testing was pursued at three applied voltage settings of 3.5 V, 4.0 V and 4.5 V. Comparable separations were established independent of voltage suggesting good performance of the device of the present invention as shown in
The compositions of the device of the present invention can also be used to improve the current efficiency of prior art suppressor devices. In this example a capillary suppressor (Thermo Scientific™ 0.4 mm ACES suppressor as described in U.S. Pat. Nos. 8,415,168 and 8,216,515) is filled with a composition comprising of 90% strong acid cation exchange resin and 10% weak acid cation exchange resin. The combination was tested using a capillary ion chromatography system using an IonPac AS19 (0.4×250 mm) chemistry. An eluent concentration of 20 mM KOH was used for the analysis. The suppressor was tested using a constant voltage of 4 V. The current efficiency of the device under the test conditions was 75% as opposed to a prior art suppressor that had 100% strong acid resin and operated at a current efficiency of 6%. This improvement of current efficiency would result in lower wattage and possibly improved device life time. The device was tested using a sample mixture comprising of fluoride (peak 1, 0.75 mg/L), chlorite (peak 2, 2.5 mg/L), bromate (peak 3, 5 mg/L), chloride (peak 4, 1.5 mg/L), nitrite (peak 5, 3.75 mg/L), chlorate (peak 6, 6.25 mg/L), bromide (peak 7, 6.25 mg/L), nitrate (peak 8, 6.25 mg/L), carbonate (peak 9, not quantified) and sulfate (peak 10, 7.5 mg/L. Excellent suppression was established with good peak shapes using the device of the present invention as shown in
A Thermo Scientific™ CERS 2 mm suppressor according to the present invention was also assembled (available from Thermo Fisher Scientific) as described in the U.S. Pre-Grant Publication 2014/0134050A1. The eluent channel of the device was packed with anion exchange resin with a composition comprising of 90% by weight of a 8% crosslinked quaternary ammonium based strong anion exchange resin and 10% of a tertiary amine based weak base anion exchange resin. The device was tested using an IonPac™CS12A column 2×250 mm and 20 mM methanesulfonic acid eluent. The flow rate was 0.25 mL/min and the injection loop was 5 μL. The CERS 2 mm suppressor was tested at various applied constant voltages to determine the effect of voltage on performance. A sample comprising of a mixture of cation standards was used for this study. The sample consisted of lithium (peak 1, 0.5 mg/L), sodium (peak 2, 2 mg/L), ammonium (peak 3, 2.5 mg/L), potassium (peak 4, 5 mg/L), magnesium (peak 5, 2.5 mg/L) and calcium (peak 6, 5 mg/L). The results as shown in
Further the peak asymmetry was also consistent across various voltages suggesting no shape change with applied voltage. A summary of the results are presented in Tables 7 and 8 below.
The AERS suppressor from Example 2 was also used for testing an eluent containing solvents. The device was tested using a system setup with an IonPac™ AS11-HC 2×250 mm column.
A gradient was used in this work as listed below along with 20% methanol (v/v) as the solvent.
A mixture comprising of standard anions such as fluoride (peak 1, 2 mg/L), chloride (peak 2, 10 mg/L), nitrite (peak 3, 10 mg/L), bromide (peak 4, 10 mg/L), nitrate (peak 5, 10 mg/L), carbonate (peak 6, not determined), sulfate (peak 7, 10 mg/L) and phosphate (peak 8, 20 mg/L) was analyzed. The effect of applied voltage on the displayed peak efficiency was studied. Excellent performance can be inferred from both the chromatogram shown in
The device of Example 6 was also tested using an eluent comprising of borate. The column used in this work was an IonPac™ AS22 2×250 mm column. 200 mM boric acid was pumped into an eluent generator cartridge and a potassium hydroxide gradient was used in this work. The gradient conditions are listed below.
A standard mixture of seven anions included fluoride (peak 1, 2 mg/L), chloride (peak 2, 10 mg/L), nitrite (peak 3, 10 mg/L), bromide (peak 4, 10 mg/L), nitrate (peak 5, 10 mg/L), phosphate (peak 6, 20 mg/L) and sulfate (peak 7, 10 mg/L) was analyzed. The effect of applied voltage on the displayed peak efficiency was studied. Excellent performance can be inferred from both the chromatogram shown in
A 4 mm AERS suppressor of the present invention from example 3 was used in this work. The suppressor was tested with an IonPac™ AS23 4×250 mm column at a flow rate of 1 mL/min using an eluent comprising of 4.5 mM sodium carbonate and 0.8 mM sodium bicarbonate eluent. The device was operated at a constant voltage of 4 V. A standard mixture of seven anions (same as example 8) was analyzed using this setup. Excellent peak shapes were observed as shown in
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