Patent Application
20230341361
This invention is directed to monitoring suppressors for failure and mitigating downstream consequences of the failure. In particular, monitoring systems are described that detect deviations from normal operation of a suppressor and in response to the deviation adjust aqueous ion flow to a detector.
Ion chromatography (IC) is a well-established analytical technique and for the past 40 years or so has been the preferred method for the determination of inorganic anions and small organic anions. IC is also used widely for the determination of inorganic cations, as well as carbohydrates and amino acids.
A suppressor is one of the key components in an IC system. Suppressor technology has evolved over the decades, but the fundamental function of the suppressor remains the same: to reduce the background conductivity of the eluent and increase the conductivity of the analytes via the ion-exchange process. The de-salting of the eluent increases the response of the analytes in the subsequent conductivity detection.
In recent years mass spectrometry (MS) has become widely accepted for selective and sensitive detection in the analysis of large and small molecules. When coupled with liquid chromatography, including ion chromatograph (IC), atmospheric pressure ionization (API) MS (mostly in the form of electrospray ionization (ESI)) is a powerful tool for identification of compounds via determination of molecular mass or characteristic fragmentation of the analyte. IC interfaced with MS plays a major role in a variety of applications including trace analysis of inorganic and organic anions, speciation analysis and metallomics, mass isotopomer measurements of ionic species, and glycans and other complex carbohydrates analysis.
The eluents used in IC separation often contain non-volatile salts which are not compatible with ESI-MS. The suppressor is a critical device used to convert the non-volatile salt into water or the volatile acid form (i.e. acetic acid). For glycans and other complex carbohydrates analysis, various complex gradients using high concentration of sodium acetate (NaOAc)/sodium hydroxide (NaOH) eluents are often required. When the suppressor fails, the non-volatile salts having concentration up to 350 mM will enter the ESI-MS and cause extensive shutdown for cleaning and maintenance of the mass spectrometer. Suppressor failures often involve loss of water supply in the regenerant channels 106 from water reservoir runout or pump shutdown or broken connecting tubing. Another common failure mode is suppressor leaks due to excessive backpressure downstream caused by obstructions and clogging, such as by salts and sample components in electrospray capillary of the ESI-MS detector.
Accordingly, there remains a need for an improved suppressor. Suppressors and systems that can avoid system damage and downtime due to periodic suppressor failures are highly desirable.
Systems, methods, and products to address these and other needs are described herein with respect to illustrative, non-limiting, implementations. Various alternatives, modifications and equivalents are possible.
According to a first aspect, a suppressor is described. The suppressor includes one or more channels. Each channel includes an inlet and an outlet. The suppressor also includes a flow path for each of the channels. Each flow path includes an upstream path to the inlet, a channel stream path through the channel and connecting the inlet to the outlet, and a downstream path from the outlet. One or more of a measurement probe is positioned in the flow path.
According to a second aspect, a system for monitoring and controlling aqueous ion flow is described. The system comprises a suppressor including a sample channel having a sample inlet and a sample outlet, and a regenerant channel having a regenerant inlet and a regenerant outlet. An eluent source is fluidly connected to the sample inlet, and a regenerant source is fluidly connected to the regenerant inlet. The system also comprises a sample path and a regenerant path. The sample path includes a sample upstream path connecting the eluent source to the sample inlet, a sample stream path through the sample channel, and a sample downstream path from the sample outlet. The regenerant path includes a regenerant upstream path connecting the regenerant source to the regenerant inlet, a regenerant stream path through the regenerant channel, and a regenerant downstream path from the regenerant outlet. One or more measurement probes are positioned in the sample path, the regenerant path, or the sample path and the regenerant path. A monitoring circuit is coupled to the measurement probe. The monitoring circuit provides a signal indicative of a property of a fluid measured by the measurement probe. A flow controller is connected to the monitoring circuit and is configured to control the sample downstream path.
According to a third aspect, a method for controlling a suppressor is described. The method includes providing an eluent to the suppressor and monitoring a property of the suppressor. The method also includes directing a sample downstream path of the eluent from the suppressor to a detector if the monitored property is within of a predefined range or preventing the sample downstream path from reaching the detector if the monitored property is outside of the predefined range.
The suppressor, systems and methods described herein can avoid damage or downtime to elements such as detectors couple to the suppressor due to suppressor failures.
The foregoing and other features and advantages of the present embodiments will be more fully understood from the following detailed description of illustrative embodiments taken in conjunction with the accompanying drawings.
The figures referred to above are not drawn necessarily to scale, should be understood to provide a representation of particular embodiments, and are merely conceptual in nature and illustrative of the principals involved. The same reference numbers are used in the drawings for similar or identical components and features shown in various alternative embodiments.
In the description of the invention herein, it is understood that a word appearing in the singular encompasses its plural counterpart, and a word appearing in the plural encompasses its singular counterpart, unless implicitly or explicitly understood or stated otherwise. Furthermore, it is understood that for any given component or embodiment described herein, any of the possible candidates or alternatives listed for that component may generally be used individually or in combination with one another, unless implicitly or explicitly understood or stated otherwise. Moreover, it is to be appreciated that the figures, as shown herein, are not necessarily drawn to scale, wherein some of the elements may be drawn merely for clarity of the invention. Also, reference numerals may be repeated among the various figures to show corresponding or analogous elements. Additionally, it will be understood that any list of such candidates or alternatives is merely illustrative, not limiting, unless implicitly or explicitly understood or stated otherwise. In addition, unless otherwise indicated, numbers expressing quantities of ingredients, constituents, reaction conditions and so forth used in the specification and claims are to be understood as being modified by the term “about.”
Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the subject matter presented herein. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the subject matter presented herein are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical values, however, inherently contain certain errors necessarily resulting from the statistical dispersion found in their respective testing measurements.
The system 200 also includes a sample path 214, a regenerant path 264 and one or more measurement probes 222. The sample path 214 includes a sample upstream path 216 connecting the eluent source 204 to the sample inlet 210, a sample stream path 218 through the sample channel 208, and a sample downstream path 220 from the sample outlet 212. The regenerant path 264 includes a regenerant upstream path 266 connecting the regenerant source 254 to the regenerant inlet 260, a regenerant stream path 268 through the regenerant channel 258, and a regenerant downstream path 270 from the regenerant outlet 262. The one or more measurement probes 222 are positioned in the sample path 214, the regenerant path 264, or in both the sample path 214 and the regenerant path 264.
The system 200 also includes a monitoring circuit 224 and a flow controller 226. The monitoring circuit 224 is coupled to the measurement probe 222 and provides a signal indicative of a property of a fluid measured by the measurement probe 222. For example, the measurement probe 222 can provide a measurement signal that is indicative of an eluent in the sample path 214, or a signal that is indicative of a regenerant in the regenerant path 264. The flow controller 226 is also coupled or connected to the monitoring circuit 224 and is configured to control the sample downstream path 220. The signal can be an average signal. For example, the signal can be averaged over a period of time. The signal can also be periodically sampled, such as with a sampling period of 0.1 millisecond or more.
In some implementations, the flow controller 226 provides the sample downstream path 220 to the detector 206 if the signal indicative of a property of a fluid being measured by the measurement probe 222 of the eluent is maintained within a predefined range. For example, the flow controller 226 can be a pump providing eluent flow in the sample path 214 and provides the de-salted eluent 110 (
In some implementations, the system 200 also includes a computer or computer sub-system 228. The computer 228 includes one or more processors such as a CPU 230, memory 232, and a user interface 234. Memory 232 may include, for example, electronic memory devices, such as random-access memory (RAM), read-only memory (ROM), programmable read-only memory (PROM), electrically erasable programmable read only memory (EEPROM), and flash memory. Memory 232 may also include electromechanical memory, such as magnetic disk drives, tape drives, thumb drives, and optical disk drives. The user interface 234 can include, for example, a keyboard, a touch control screen, a monitor, a mouse, a speaker, a microphone and the like. The computer 228 can be connected to the other components of the system 200. The computer can be a physically integrated part of the system 200, such as encased in a single unit, or directly physically attached to components or a unit housing the components of system 200. Physical attachment includes electric wire connections and the like for data and signal transfer between the computer 228 and electrical components of the rest of the system 200. The computer can also include a physical or a remote (e.g., Wi-Fi, Zigbee, Bluetooth) connection to other computers or a server, such as the cloud. The computer 228 can also be partially, or wholly wirelessly connected to the electrical components of the system 200, such as the detector 206, the measurement probe 222 and the flow controller 226.
The predefined range can be a parameter used in an algorithm saved to the memory 232 and executed by the CPU 230 of the computer 228. The predefined range can be provided by a user as an input through the user interface 234 or can be a default value written into the algorithm. In some implementations, the predefined range has an upper bound. In some implementations, the predefined range has a lower bound. In some implementations, the predefined range has an upper and lower bound. In some implementations, the predefined range is an exclusion range, where the flow controller 226 does not provide the sample downstream path 220 to the detector 206 if the signal is maintained within the exclusion range.
The system 200 can include other components and subsystems. For example, a power source 236. The power source 236 can be a physical power source, such as a plug to a wall socket, a battery, a contactless inductive power source, or a combination of these. Components and subcomponents of the system 200 can have independent power sources 236. The system 200 can also include actuators, pumps, microcontrollers, heaters, chillers, tubing, pumps, cables, columns (e.g., separation or chromatograph columns), and combinations of these.
In some implementations, the system 200 is implemented as a liquid chromatography system. In such implementations the eluent source 204 is an output from a chromatography column. In some implementations, the detector 206 is a mass spectrometer, such as an ESI mass spectrometer. In some implementations, the detector 206 is a conductivity detector. In some implementations, more than one detector 206 is used, such as a conductivity detector and a mass spectrometer. In some implementations, the system 200 is implemented as liquid chromatography system wherein the suppressor 202 removes salts, such as a buffer (e.g., phosphate buffers) used in an aqueous liquid chromatograph system (e.g., water combined with polar solvents such as alcohols, acetonitrile, acetone, tetrahydrofuran and dimethyl sulfoxide).
In some implementations, the one or more channels 303 include the sample channel 208 having a sample inlet 210 and a sample outlet 212 and a regenerant channel 258 having a regenerant inlet 260 and a regenerant outlet 262 (
In some implementations, the measurement probe 222 is a temperature probe, such as a thermocouple or a thermal IR sensor. In some implementations, the measurement probe 222 is a pressure sensor. In some implementations, the measurement probe 222 is a flow meter. In implementations using more than one measurement probe 222, the measurement probes 222 can be the same kind, such as both being a temperature probe. In some other implementations using more than one measurement probe 222, the measurement probes 222 can be different kinds, such as a temperature probe and a pressure sensor. In some implementations, the measurement probes are positioned in the sample path 214 and the regenerant path 264. In some implementations, the measurement probes 222 are positioned only in the sample path 214. In some implementations, the measurement probes 222 are positioned only in the regenerant path 266. In some implementations, the measurement probes may be positioned outside of the sample path 214 and the regenerant path 264.
As depicted in
In some implementations, a position proximate to the inlet 310 is a position that is at a distance 49% or less (e.g., 40% or less, 30% or less, 20% or less, 10% or less) of a total length of the channel 303 from the inlet 310; and a position that is proximate to the outlet 312 is a position that is at a distance of 49% or less (e.g., 40% or less, 30% or less, 20% or less, 10% or less) of a total length of the channel 303 from the outlet 312. In the figures, the total length of the channel 303 corresponds to the channel stream path 318.
In some implementations, at least one of the measurement probes 222 is positioned in the downstream path 320, such as the sample downstream path 220 or the regenerant downstream path 270. In some implementations, at least one of the measurement probes 222 is positioned in the upstream path 316, such as the upstream sample path 216 or the upstream regenerant path 266. In some implementations, at least one measurement probe 222 is positioned in the downstream path 320, such as the sample downstream path 220 or the downstream regenerant path 270; and at least one measurement probe 222 is positioned in the upstream path 316, such as the sample upstream path 216, or the upstream regenerant path 266. In some implementations, at least one of the measurement probes 222 is positioned in the downstream path 320 proximate to the outlet 312. In some implementations, at least one of the measurement probes 222 is positioned in the sample downstream path 220 proximate to the outlet 212. In some implementations, at least one of the measurement probes 222 is positioned in the downstream regenerant path 270 proximate to the outlet 262. In some implementations, at least one of the measurement probes 222 is positioned in the upstream path 316 proximate to the inlet 310. In some implementations, at least one of the measurement probes 222 is positioned in the upstream sample path 216 proximate to the inlet 210. In some implementations, at least one of the measurement probes 222 is positioned in the upstream regenerant path 266 proximate to the inlet 260.
In some implementations, the suppressor 202 further includes the flow controller 226 which is coupled to the monitoring circuit 332 and the flow controller 226 is configured to control the downstream path 320 in response to the signal. In some implementations, the channel 303 includes the sample channel 208 and the downstream path/sample downstream path 320, 220 directs the fluid from the sample channel 208 into the detector 206 when the signal is maintained within the predefined range, and the downstream path 320/sample downstream path 220 prevents the fluid from entering the detector 206 when the signal is outside of the predefined range. In some implementations, the detector 206 is a mass spectrometer.
In some implementations, the probe 222 includes a working end 307 in contact with the fluid in the fluid path 314, wherein the working end 307 is positioned flush to a wall of a conduit defining the fluid path (
The flow controller 226, configured in this implementation as a 6-port injection valve, is installed between the suppressor 202 (or the optional conductivity detector 206a) and the mass spectrometer 206b. When the flow controller 226 is in the A position, the eluent flows through the suppressor 202 and to the mass spectrometer 206b, and the regenerant flows through the suppressor 202. The figure also shows the valve in a B position (bottom right of the figure). When the flow controller 226 is in the B position, the regenerant pump 410 delivers the regenerant to the mass spectrometer 206b, and the eluent does not flow into the mass spectrometer 206b.
When the signal from the monitoring circuit 224 is within the predefined range, the flow controller 226 is in the A position. When the signal from the monitoring circuit 224 is outside of the predefined range, the flow controller 226 is in the B position. The flow controller 226 can also include, or alternatively is, the eluent pump 404. For example, the eluent pump 404 can run normally when the signal from the monitoring circuit 224 is within the predefined range, and the eluent pump 404 can be shut off when the signal from the monitoring circuit 224 is outside of the predefined range.
The suppressor 202 can be used to mitigate damage or down time to detectors coupled to the suppressor. For example, the suppressor can be included in a liquid chromatograph system as described herein. For illustrative purposes, and without limiting the uses, some further examples are discussed below.
Elements as labeled are as previously described with additional details described below.
Experimental Conditions.
IC system: Thermo Scientific Dionex ICS-6000.
Eluent: 10 mM NaOAc/100 mM NaOH during 0-5 min, 10 mM NaOAc/100 mM NaOH—100 mM NaOAc/100 mM NaOH during 5-30 min, 10 mM NaOAc/100 mM NaOH during 30-60 min.
Eluent flow rate: 0.25 mL/min.
Suppressor: Thermo Scientific Dionex ERD 500 2-mm.
Suppressor current: 150 mA.
Regenerant flow rate: 1.5 mL/min during 0-10 min, 0 mL/min during 10-20 min, 1.5 mL/min during 20-60 min.
Compartment temperature: 30° C.
Multimeter: Fluke 289 True-RMS Data Logging Multimeter.
Detector: conductivity.
Data recording: Thermo Scientific Dionex Chromeleon7.
Experimental Conditions.
IC system: Thermo Scientific Dionex ICS-6000.
Eluent: 50 mM NaOAc/100 NaOH.
Eluent flow rate: 0.25 mL/min.
Suppressor: Thermo Scientific Dionex ERD 500 2-mm.
Suppressor current: 150 mA.
Regenerant flow rate: (A) 1.5 mL/min during 0-10 min, 0 mL/min during 10-25 min, 1.5 mL/min during 20-30 min; (B) 1.5 mL/min during 0-10 min, 1.5-0 mL/min during 10-20 min, 0 mL/min during 20-25 min, 1.5 mL/min during 20-30 min.
Compartment temperature: 25° C.
Multimeter: Fluke 289 True-RMS Data Logging Multimeter.
Detector: conductivity.
Data recording: Thermo Scientific Dionex Chromeleon 7.
Experimental Conditions.
IC system: Thermo Scientific Dionex ICS-6000.
Eluent: 10 mM KOH during 0-10 min, 10-100 mM KOH during 10-30 min, 100 mM KOH during 30-60 min.
Eluent flow rate: 0.25 mL/min.
Suppressor: Thermo Scientific Dionex ADRS 600 2-mm.
Suppressor current: 62 mA.
Regenerant flow rate: 0.25 mL/min during 0-15 min, 0 mL/min during 15-25 min, 1.5 mL/min during 25-60 min.
Compartment temperature: 25° C.
Multimeter: Fluke 289 True-RMS Data Logging Multimeter.
Detector: conductivity.
Data recording: Thermo Scientific Dionex Chromeleon 7.
Experimental Conditions.
IC system: Thermo Scientific Dionex ICS-6000.
Eluent: 100 mM KOH.
Eluent flow rate: 0.25 mL/min.
Suppressor: Thermo Scientific Dionex ADRS 600 2-mm.
Suppressor current: 62 mA.
Regenerant flow rate: 0.25 mL/min.
Compartment temperature: 25° C.
Multimeter: Fluke 289 True-RMS Data Logging Multimeter.
Detector: conductivity.
Data recording: Thermo Scientific Dionex Chromeleon 7.
A pressure transducer from an ICS-5000+DP pump was connected to the eluent outlet of the suppressor Dionex ERD 500 2-mm. A series of backpressure tubing were connected to the outlet of the conductivity detector to apply varied backpressure to the simulate obstruction of the eluent flow at the downstream of the suppressor. The conductivity detector was used to monitor the effect of elevated backpressure on suppression efficiency (not a direct indication of how much salt broke through). Backpressure tubing that applies 300, 400, 500, and 600 psi at the flow rate of 0.25 mL/min was connected to the outlet of the conductivity detector for approximately 1 min at each pressure value, with approximately 4 min interval between each pressure exertion. As shown by the plotted data in
Experimental Conditions.
IC system: Thermo Scientific Dionex ICS-6000.
Eluent: 10 mM NaOAc/100 NaOH.
Eluent flow rate: 0.25 mL/min.
Suppressor: Thermo Scientific Dionex ERD 500 2-mm.
Suppressor current: 150 mA.
Regenerant flow rate: 1.5 mL/min.
Compartment temperature: 30° C.
Detector: conductivity.
Pressure sensor: transducer from ICS-5000+DP.
Data recording: Thermo Scientific Dionex Chromeleon 7.
Those having skill in the art, with the knowledge gained from the present disclosure, will recognize that various changes can be made to the disclosed apparatuses and methods in attaining these and other advantages, without departing from the scope of the present disclosure. As such, it should be understood that the features described herein are susceptible to modification, alteration, changes, or substitution. For example, it is expressly intended that all combinations of those elements and/or steps which perform substantially the same function, in substantially the same way, to achieve the same results are within the scope of the embodiments described herein. Substitutions of elements from one described embodiment to another are also fully intended and contemplated. The specific embodiments illustrated and described herein are for illustrative purposes only, and not limiting of that which is set forth in the appended claims. Other embodiments will be evident to those of skill in the art. It should be understood that the foregoing description is provided for clarity only and is merely exemplary. The spirit and scope of the present disclosure is not limited to the above implementation and examples but is encompassed by the following claims. All publications and patent applications cited above are incorporated by reference in their entirety for all purposes to the same extent as if each individual publication or patent application were specifically and individually indicated to be so incorporated by reference.
The present application claims the priority benefit from U.S. Patent Application Ser. No. 63/363,535, filed Apr. 25, 2022, which is hereby incorporated by reference herein in its entirety for all purposes.
| Number | Date | Country | |
|---|---|---|---|
| 63363535 | Apr 2022 | US |
