Patent Application
20200200720
The present disclosure generally relates to flow cells for pressurized chromatography or extraction systems. In particular, the present disclosure relates to optical detector flow cells.
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, an optical flow cell is disclosed. The optical flow cell includes an inlet portion configured to receive a highly compressible fluid. The optical flow cell also includes an inlet transition portion having an internal volume and internal geometry configured to receive the highly compressible fluid from the inlet portion. The optical flow cell also includes an optical path portion configured to receive the highly compressible fluid from the inlet transition portion and direct the highly compressible fluid along an optical flow path. The internal volume and the internal geometry of the inlet transition portion are configured to minimize turbulence and eddies within the highly compressible fluid as it travels through the optical flow path. In a non-limiting example, an internal thickness of the inlet transition portion is configured to reduce turbulence and eddies within the highly compressible fluid as it travels through the optical flow path. In another non-limiting example, the inlet portion is configured to introduce the highly compressible fluid into the inlet transition portion at an angle configured to reduce turbulence and eddies within the highly compressible fluid. In another non-limiting example, the inlet transition portion has an annular internal geometry configured to direct the highly compressible fluid along an annular flow path. In another non-limiting example, the annular internal geometry is oriented around a central axis of the optical path portion. In another non-limiting example, the optical flow cell also includes an end portion configured to direct the annular flow path inward toward a central axis of the inlet transition portion and reverse a flow direction of the highly compressible fluid prior to directing the highly compressible fluid along the optical flow path. In another non-limiting example, the inlet transition portion has a substantially spiraling internal geometry. In another non-limiting example, the inlet transition portion has a greater internal volume proximal to the optical flow portion than proximal to the inlet portion. In another non-limiting example, the optical flow cell also includes a light source configured to direct light along the optical flow path. In another non-limiting example, the inlet transition portion is a gasket.
According to another aspect of the present technology, another optical flow cell is disclosed. The optical flow cell includes an inlet portion configured to receive a highly compressible fluid. The optical flow cell also includes an annular inlet transition portion having a substantially cylindrical internal volume and configured to receive the highly compressible fluid from the inlet portion. The optical flow cell also includes an optical path portion configured to receive the highly compressible fluid from the annular inlet transition portion and direct the highly compressible fluid along an optical flow path. In a non-limiting example, the optical flow cell also includes a conical portion configured to direct the highly compressible fluid toward a central axis of the optical path portion. In another non-limiting example, at least a part of the optical path portion is disposed within a cavity defined by the annular inlet transition portion. In another non-limiting example, the optical flow cell also includes an end portion configured to direct the highly compressible fluid inward toward a central axis of the inlet transition portion and reverse a flow direction of the highly compressible fluid prior to directing the highly compressible fluid along the optical flow path. In another non-limiting example, the inlet transition portion is a gasket.
According to another aspect of the present disclosure, another optical flow cell is disclosed. The optical flow cell includes an inlet portion configured to receive a highly compressible fluid. The optical flow cell also includes an inlet transition portion having a spiraling internal geometry and configured to receive the highly compressible fluid from the inlet portion. The optical flow cell also includes an optical path portion configured to receive the highly compressible fluid from the inlet transition portion and direct the highly compressible fluid along an optical flow path. In a non-limiting example, the inlet transition portion has a larger internal volume proximal to the optical path portion than proximal to the inlet portion. In another non-limiting example, the inlet transition portion is a gasket.
The above aspects of the technology provide numerous advantages. For example, the various designs and geometries disclosed herein can prevent eddies within the CO2-based mobile phase and therefore prevent localized pressure changes and changes in the refractive index of the fluid due to density variation. Overall, this invention increases the signal to noise ratio 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 optical detector flow cells for use within a chromatography 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 flow cell containing 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=εlC (1)
A is the dimensionless absorbance, ε is a molar absorptivity coefficient (L mol−1 cm−1), l 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). Optimizing the response of optical detectors can be achieved by maximizing the signal to noise ratio generated by the amount injected. Accordingly, in addition to efforts to maximize the signal generated, efforts to reduce the baseline noise of the detector have a very impactful effect on detector performance.
Changes in the refractive index (RI) of a fluid inside the optical path of the detector cell can also result in undesired detector noise. Such changes are tolerable if they occur infrequently, or change slowly. However, changes in fluid RI on the time scale of a chromatographic peak are very undesirable for low-noise, sensitive detection. In comparison to liquid chromatography (LC), supercritical fluid chromatography (SFC) employing a highly compressible, often CO2-based, mobile phase has a greater number of possible variables affecting the RI of the mobile phase. For example, the RI is related to the density of the mobile phase. Since density is controlled by temperature and pressure, these parameters have a direct influence on the RI of the mobile phase. Accordingly, pressure and temperature fluctuations can contribute to high levels of detector noise and must be managed in for CO2-based chromatography with optical detection.
Modern CO2-based chromatography systems are often designed to reduce system pressure noise and to thermally pre-condition the mobile phase prior to entry into the flow cell. However, the optical detector flow cells are largely unchanged from the LC cells they were derived from. Most commonly, the cell is modified with an increased pressure rating to accommodate the pressurized nature of the SFC mobile phase.
An example of the formation of flow eddies or turbulence is shown in
One skilled in the art will recognize that the flow direction and the direction of the light through the flow cell can be in the same direction or in opposite directions. The optical bore may be a taper slit or a straight-through design. The outlet cross sectional area of the optical bore may be matched to the inlet cross sectional area for optimal light throughput. The inlet and outlet cross sections may not be the same geometry. For example, the inlet may have a round cross section while the outlet may have a rectangular cross section.
An important aspect of flow cell design is to minimize swept and unswept volumes in the chromatographic mobile phase flow path. Minimizing these volumes is important to maintain chromatographic peak fidelity. Further, inlet and outlet tubing can be arranged in a ‘knitted’ geometry. Such consecutive left and right turns help to minimize band broadening due to longitudinal diffusion in a laminar flow profile.
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.
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. 62/782,585 filed Dec. 20, 2018 titled “OPTICAL DETECTOR FLOW CELL FOR CO2-BASED CHROMATOGRAPHY,” the entire contents of which is hereby incorporated by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 62782585 | Dec 2018 | US |
