The present disclosure generally relates to pressurized fluid systems used in chromatography or extraction systems. In particular, the present disclosure relates to systems and methods for extracting gaseous or highly compressible components from a mobile phase.
Chromatography involves the flowing of a mobile phase over a stationary phase to effect separation. To speed-up and enhance the efficiency of the separation, pressurized mobile phases are introduced. Carbon dioxide based chromatographic systems use CO2 as a component of the mobile phase flow stream, and the CO2 based mobile phase is delivered from pumps and carried through the separation column as a pressurized liquid. The CO2 based mobile phase is used to carry components of the analytes in a sample through the chromatography column and to a detection system.
Performing optical detection within a chromatography or extraction system raises a number of challenges, especially when dealing with a highly compressible mobile phase, such as a CO2-based mobile phase. Technology for avoiding pressure changes within an optical detector would be beneficial and highly desirable.
According to one aspect of the present technology, a method for extracting a gaseous component from a mobile phase is disclosed. The method includes pumping a compressible mobile phase through a column. The method also includes extracting a compressible portion of the mobile phase from the output of the column upstream of a detector using a separator. The method also includes directing the substantially liquid component of the mobile phase to the detector. In a non-limiting example, the detector is a low pressure liquid optical detector. In another non-limiting example, the compressible portion of the mobile phase is CO2 and the separator is a gas-liquid separator. In another non-limiting example, the method also includes decompressing the mobile phase downstream of the column and upstream of the gas-liquid separator using a back pressure regulator. In another non-limiting example, the method also includes directing the extracted gaseous CO2 to waste. In another non-limiting example, the method also includes preventing degassing of residual CO2 downstream of the detector using a back pressure regulator.
According to another aspect of the present technology, a method for extracting CO2 from a mobile phase is disclosed. The method includes pumping a CO2-based mobile phase through a column. The method also includes introducing a makeup fluid downstream of the column and upstream of a detector using a makeup pump. The method also includes extracting CO2 from the mobile phase upstream of the detector. The method also includes directing the substantially liquid component of the mobile phase to a detector. In a non-limiting example, the detector is a low pressure liquid optical detector. In another non-limiting example, the makeup pump is configured to pump a makeup fluid having a same composition as a mobile phase solvent exiting the column. In another non-limiting example, the method also includes decompressing the mobile phase downstream of the column and upstream of the gas-liquid separator using a back pressure regulator. In another non-limiting example, the method also includes controlling the introduction of the makeup fluid in order to maintain a constant liquid flow rate through the detector. In another non-limiting example, the method also includes controlling the introduction of the makeup fluid according to a flow gradient inverse to a modifier pump flow gradient. In another non-limiting example, the method also includes preventing degassing of residual CO2 downstream of the detector using a low pressure back pressure regulator.
According to another aspect of the present technology, a system for extracting CO2 from a mobile phase is disclosed. The system includes a mobile phase pump configured to pump a CO2-based mobile phase through a column. The system also includes a pressure control device configured to decompress the mobile phase downstream of the column. The system also includes a gas-liquid separator located downstream of the column and configured to extract CO2 from the mobile phase. The system also includes a detector located downstream of the gas-liquid separator and configured to analyze a substantially liquid portion of the mobile phase. In a non-limiting example, the system also includes a makeup pump configured to introduce a makeup fluid downstream of a column. In another non-limiting example, the makeup fluid has a same composition as a mobile phase solvent exiting the column. In another non-limiting example, the system also includes a computing device configured to control an operation of the makeup pump in order to maintain a constant fluid flow rate through the detector. In another non-limiting example, the system also includes a computing device configured to control an operation of the makeup pump in order to introduce the makeup fluid according to a flow gradient inverse to a modifier pump flow gradient. In another non-limiting example, the system also includes a back pressure regulator located downstream of the detector and configured to prevent degassing of residual CO2. In another non-limiting example, the pressure control device is a back pressure regulator.
The above aspects of the technology provide numerous advantages. For example, since the mobile phase is no longer pressurized, detectors can be directly borrowed from liquid chromatography and employed without modification. According to traditional techniques, such LC detectors can often require modifications, such as high pressure flow cells, for use in a CO2-based chromatography systems. Such detectors could include UV-Vis, PDA, fluorescence, refractive index, etc. An additional advantage to this system is a reduction in noise in the detector. Since, after removal of the compressible component, the mobile phase is nearly incompressible, pressure fluctuations no longer significantly contribute to baseline noise. Further, eddying within the optical path no longer results in large optical noise. Overall, this invention increases the signal and decreases the noise of optical detection when used with a CO2-based mobile phase.
It should be appreciated that all combinations of the foregoing concepts and additional concepts discussed in greater detail below (provided such concepts are not mutually inconsistent) are contemplated as being part of the inventive subject matter disclosed herein. In particular, all combinations of claimed subject matter appearing at the end of this disclosure are contemplated as being part of the inventive subject matter disclosed herein. It should also be appreciated that terminology explicitly employed herein that also may appear in any disclosure incorporated by reference should be accorded a meaning most consistent with the particular concepts disclosed herein.
One of ordinary skill in the art will understand that the drawings primarily are for illustrative purposes and are not intended to limit the scope of the inventive subject matter described herein. The drawings are not necessarily to scale; in some instances, various aspects of the subject matter disclosed herein may be shown exaggerated or enlarged in the drawings to facilitate an understanding of different features. In the drawings, like reference characters generally refer to like features (e.g., functionally similar and/or structurally similar elements).
The features and advantages of the present disclosure will become more apparent from the detailed description set forth below when taken in conjunction with the drawings.
Following below are more detailed descriptions of various concepts related to, and embodiments of, methodologies, apparatus and systems for extracting a gaseous component, such as CO2, from a mobile phase prior to detection within a chromatography or extraction system. It should be appreciated that various concepts introduced above and discussed in greater detail below may be implemented in any of numerous ways, as the disclosed concepts are not limited to any particular manner of implementation. Examples of specific implementations and applications are provided primarily for illustrative purposes.
As used herein, the term “includes” means includes but is not limited to, the term “including” means including but not limited to. The term “based on” means based at least in part on.
Optical detection involves passing light through a sample and measuring the amount of light absorbed by the sample. Example detectors include ultraviolet visible (UV-Vis) detectors and photodiode array (PDA) detectors. Each operate on Beer's law (Equation 1)
A=ε1C (1)
A is the dimensionless absorbance, ε is a molar absorptivity coefficient (L mol−1 cm−1), 1 is the light path (cm) length, and C is the concentration (mol L−1) of the analyte. Absorbtivity is an analyte-dependent physical constant. Accordingly, to increase absorbance, the path length of light within the detector cell can be increased, or the concentration of the analyte can be increased. Path length is often limited to by mechanical or manufacturing constraints and/or optimal volumes dictated by chromatographic performance. Concentration, on the other hand, is governed by amount injected and mobile phase flow rate. The amount injected and the mobile phase flow rate have an inverse relationship, so it can be challenging to optimize these parameters to improve detector response. For example, large flow rates allow for large injection volumes (pre-column dilution to avoid mass and volume overload). Additional detectors that can be used may include refractive index detectors and fluorescence detectors, which rely on different principles.
Optical detection is a concentration-sensitive detection technique. Accordingly, the response of the detector can increase if the concentration of an analyte is increased within the mobile phase. When operating with supercritical fluid chromatography (SFC) or other forms of CO2-based chromatography/extraction, one could conceivably leverage the compressible nature of the mobile phase to increase the concentration of the analyte in the mobile phase after the column and before the detector. In a non-limiting example of the present disclosure, the mobile phase is depressurized, the CO2 is removed, and the analyte is concentrated into the liquid portion of the mobile phase in order to concentrate the analyte in a CO2-based chromatography or extraction system. Such concentration can increase the response of an optical detector.
In a non-limiting example, the mobile phase can be decompressed using a BPR 407 after separation. As the lower pressure CO2 transitions to a gas, it loses its miscibility with the liquid portion (modifier) of the mobile phase. In the example embodiment shown in
In step 503, a makeup pump introduces a makeup fluid to the mobile phase downstream of the column and upstream of a detector. In a non-limiting example, the makeup pump can be controlled using a computer or other programmable processing device in order to introduce the makeup fluid at a particular flow rate downstream of the column. The makeup fluid can be introduced before a BPR, at the BPR, post-BPR, in a gas-liquid separator, or after the gas-liquid separator, according to various embodiments. In a non-limiting example, the makeup fluid has the same composition as the mobile phase solvent. In another example embodiment, the flow rate can be maintained with a reverse gradient or be used to ensure appropriate analyte transport when low or no liquid co-solvent is present, and the makeup fluid can be added post-column so as not to interfere with the separation performance of the system.
In step 505, CO2 is extracted from the mobile phase upstream of the detector. In some embodiments, a BPR is configured to decompress the mobile phase downstream of the column and upstream of the gas-liquid separator. The gas-liquid separator component may be a conventional momentum separator style gas-liquid separator, or it may be any device or feature which separates decompressed CO2 from the liquid portion of the mobile phase. The gas-liquid separator can also be configured direct the extracted CO2 to waste in some embodiments.
In step 507, the substantially liquid mobile phase, which includes the introduced makeup fluid, is directed to an optical detector. Because the mobile phase has been depressurized and the gaseous CO2 has been extracted in step 505, the detector can be a low pressure liquid optical detector. In a non-limiting example, the makeup pump can be controlled in order to introduce the makeup fluid at a rate configured to maintain a constant liquid flow rate through the detector. The makeup pump can also be controlled to introduce the makeup fluid according to a flow gradient inverse to a modifier pump flow gradient. In some embodiments, a low pressure BPR can be used to prevent degassing of residual CO2 downstream of the detector. That is, the low pressure BPR is set to control pressure upstream of itself at a high enough pressure to ensure that any residual CO2 remains dissolved in the non-compressible component of the mobile phase. Because the goal is to maintain the gas dissolved in the mobile phase, on a few hundred PSI need be applied (e.g., between about 100-500 PSI).
The memory 602 can be configured to store processor-executable instructions 608 and a computation module 610. In an example method, as described in connection with
In describing example embodiments, specific terminology is used for the sake of clarity. For purposes of description, each specific term is intended to at least include all technical and functional equivalents that operate in a similar manner to accomplish a similar purpose. Additionally, in some instances where a particular example embodiment includes a plurality of system elements, device components or method steps, those elements, components or steps can be replaced with a single element, component or step. Likewise, a single element, component or step can be replaced with a plurality of elements, components or steps that serve the same purpose. Moreover, while example embodiments have been shown and described with references to particular embodiments thereof, those of ordinary skill in the art will understand that various substitutions and alterations in form and detail can be made therein without departing from the scope of the disclosure. Further still, other aspects, functions and advantages are also within the scope of the disclosure.
Example flowcharts are provided herein for illustrative purposes and are non-limiting examples of methodologies. One of ordinary skill in the art will recognize that example methodologies can include more or fewer steps than those illustrated in the example flowcharts, and that the steps in the example flowcharts can be performed in a different order than the order shown in the illustrative flowcharts.
While various inventive embodiments have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and/or structures for performing the function and/or obtaining the results and/or one or more of the advantages described herein, and each of such variations and/or modifications is deemed to be within the scope of the inventive embodiments described herein. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be examples and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the inventive teachings is/are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific inventive embodiments described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that inventive embodiments may be practiced otherwise than as specifically described. Inventive embodiments of the present disclosure are directed to each individual feature, system, article, material, kit, and/or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and/or methodologies, if such features, systems, articles, materials, kits, and/or methodologies are not mutually inconsistent, is included within the inventive scope of the present disclosure.
Also, the technology described herein may be embodied as a method, of which at least one example has been provided. The acts performed as part of the method may be ordered in any suitable way. Accordingly, embodiments may be constructed in which acts are performed in an order different than illustrated, which may include performing some acts simultaneously, even though shown as sequential acts in illustrative embodiments.
This application claims the benefit of and priority to U.S. Provisional Patent Application No. 62/782,579 filed Dec. 20, 2018 titled “SYSTEM AND METHOD FOR EXTRACTING CO2 FROM A MOBILE PHASE,” the entire contents of which is hereby incorporated by reference in its entirety.
Number | Date | Country | |
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62782579 | Dec 2018 | US |