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HK1193068A - Methods and devices for open-bed atmospheric collection for supercritical fluid chromatography - Google Patents

Methods and devices for open-bed atmospheric collection for supercritical fluid chromatography Download PDF

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Publication number
HK1193068A
HK1193068A HK14106703.9A HK14106703A HK1193068A HK 1193068 A HK1193068 A HK 1193068A HK 14106703 A HK14106703 A HK 14106703A HK 1193068 A HK1193068 A HK 1193068A
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Hong Kong
Prior art keywords
flow stream
collector
fluid
sample
supercritical fluid
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HK14106703.9A
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Chinese (zh)
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HK1193068B (en
Inventor
Ziqiang Wang
Steve ZULLI
Daniel ROLLE
Chuping LUO
Harbaksh Sidhu
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Waters Technologies Corporation
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Publication of HK1193068A publication Critical patent/HK1193068A/en
Publication of HK1193068B publication Critical patent/HK1193068B/en

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Description

Method and apparatus for open-bed atmospheric collection of supercritical fluid chromatography
RELATED APPLICATIONS
Priority of united states provisional application number 61/498,458 filed on 17.6.2011, the entire contents of which are hereby incorporated by reference.
Technical Field
The present technology relates generally to methods and apparatus for open-bed atmospheric collection of supercritical fluid chromatography ("SFC"), and more particularly to methods and apparatus for open-bed atmospheric collection of SFC using XY-type fraction collectors (e.g., without a Z-moving collector arm).
Background
Open bed fraction collectors, such as XY type fraction collectors, have been widely used in preparative liquid chromatography equipment for flexibility, simplicity, availability, wide applicability, reliability and economy. The prior art collector may include a platform that can accommodate containers of various sizes and rack adapter configurations to hold tubes, bottles, containers, channel/funnel type fittings, and larger size containers for fraction collection. The collector may also have electronic components for automated control through a panel or via direct control (through sophisticated software communication protocols).
The actual collection of the chromatographic fractions is achieved by liquid line connections from the chromatographic instrument. After separation from the column/cartridge in the chromatography system, the fraction is transferred via a connecting tube to an XY type collector, flows through the robotic collector tip, and is collected in a container below the robotic collector tip. This type of container may be, for example, a glass tube, a bottle, a container and/or a channel adapter, which may allow fractions to be collected in larger sized containers such as large glass bottles. During the collection process, the mechanical collector arm can be moved by the operator along the receptacle according to preset methods to effect the separation and collection of the different fractions into their respective receptacles.
XY type collectors have wide applicability and can be used in a variety of chromatographic systems, from fast chromatography ("Flash"), low to medium pressure chromatography ("LPLC" and "MPLC", respectively) to high performance liquid chromatography ("HPLC"). The XY type collector can be controlled manually or by using preset methods from the panel or from programmed control via software for full automation of the chromatography system. XY type collectors, as the name implies, have adapter arms that can only travel in two dimensions, i.e. no Z-direction motion. Typically, the arm is placed over a grid-formation of an open collection vessel, such as a tube in which the sample is collected. In the case of many chromatographic devices such as "Flash", "LPLC", "MPLC" and "HPLC", no movement of the adapter arm in the Z dimension is required, since the eluate exiting the column can easily be directed downward into an open collection container under the influence of gravity alone, that is, the eluate is in the liquid or liquid-solid phase. Thus, advantages of XY type collectors include, but are not limited to, ease of use, reliability, economy, and flexibility.
Supercritical fluid chromatography ("SFC") is a high pressure, high performance chromatographic tool that can be used in place of liquid chromatography systems. Typically, today's SFC systems use a fluid (e.g., carbon dioxide) that is compressible above its supercritical point as a mobile phase (in many cases with a modified solvent) to perform the chromatographic separation and purification process. Generally, SFCs have higher efficiency, higher capacity and faster processing times than other chromatographic systems, such as HPLC. SFC can handle significantly more coarse purification and separation/purification in smaller units of measure and significantly reduce toxic organic solvent waste by using carbon dioxide. The process is therefore considered a green technology with high productivity and great economic impact.
SFC uses supercritical fluids such as carbon dioxide as the primary flow solvent. The supercritical CO2It is under controlled pressure as it flows in the SFC chromatography system. A pressure regulator, such as a back pressure regulator ("BPR"), may be used to control CO throughout the SFC system2And (4) pressure. The BPR is typically placed in the back section of the tubing of the chromatography system. Once the fluid passes through the BPR and is transferred to the collector, the fluid is depressurized and the supercritical CO is used2(and other compressible fluids) can be converted to a gaseous vapor and vented. Leaving a minimum liquid volume of sample fraction to be collected. Therefore, there is a natural phenomenon: as this decompression progresses, an aerosol (aerosol) of liquid is generated. The aerosol generated will carry the sample of interest from the separation process. Uncontrolled aerosols generated by this depressurization process can lead to sample loss and cross-contamination during post-separation collection and detection processesA problem and risk arises because the eluent is not simply dropped directly into a single open collection vessel, i.e., the eluent is at least partially aerosolized.
Due to this depressurization process that occurs when compressible fluids are used in SFC systems, existing collection designs for SFC chromatography use well-controlled collectors. For example, the collection site for the sample is enclosed within a container that can control any aerosol generated by pressure and size measures. Thus, prior art designs typically place the sample collection site inside a sealed container so that there is no physical opportunity for the aerosol to be released into the atmosphere under normal process conditions. The vessel may be made of, for example, stainless steel metal capable of withstanding the high pressures of an SFC process, or glass/polymer materials with reduced pressure control (e.g., venting) at reduced overpressure risk levels. The prior art designs require dedicated designs with significant investment in hardware and software. This hinders, among other things, the broader applicability and robustness of the collection system.
XY type collectors have not been used in SFC systems for several reasons. For example, XY type collectors include a collector arm positioned above the container, meaning that the collection location cannot be enclosed in a sealed collection container. Furthermore, the collection arm is not used to lower its tip into the container to limit the vertical movement (Z-movement, relative to the X-Y plane/horizontal movement) of the aerosol. This makes it difficult to integrate SFC devices with XY type collectors by their own design, even though such integration has many significant advantages (e.g., high productivity of SFC systems combined with flexibility, simplicity, availability, wide applicability, reliability and economy of XY type collectors).
Disclosure of Invention
The present technology relates to systems and methods for SFC that can incorporate standard XY type collectors (i.e., no Z-motion) suitable for other types of chromatography such as HPLC, MPLC, LPLC, and Flash chromatography. It also relates to SFC systems that can be coupled (manifold) to open-bed atmospheric XY type collectors without loss of sample and without cross contamination when supercritical fluids reach atmospheric (atmospheric) conditions.
The present technology enables the use of standard XY type fraction collectors in SFC. Such fraction collectors are known in the art for use in other chromatography systems and may incorporate a mechanical collector arm that can be moved along the vessel by an operator according to preset methods to effect separation and collection of the different fractions into their respective vessels. The present technology also enables the use of open bed collectors that do not require a dedicated collection vessel. For example, the present techniques do not require sealed containers made of stainless steel or some polymer or glass that can withstand high pressures.
In one aspect, the present technology features a supercritical fluid chromatography system. The system includes a pump for pumping a fluid containing a compressible fluid (e.g., CO)2) And a second pump for pumping a second flow stream comprising a modifier fluid (e.g., methanol). Typically, the modifier fluid is an incompressible fluid. The second pump is connected in parallel with the first pump. The column is located in the combined flow stream. The column is located downstream of the first and second pumps. The combined flow stream comprises the first flow stream, the second flow stream, and the sample. The detector is located downstream of the column. A gas-liquid separator is located downstream of the detector. The gas-liquid separator is configured to discharge a substantial portion of the compressible fluid while retaining a substantial portion of the sample to avoid sample loss and cross-contamination. An open-bed XY type collector is located after the gas-liquid separator.
A compressible fluid is a fluid that has a significant change in fluid density when high pressure is applied to it. In the case of SFC, the key difference between compressible and incompressible fluids is the way the different fluids behave when pressure is applied to them. In the case of an incompressible fluid such as water or methanol, applying pressure at one point will produce the same pressure at all other points in the system at once.
In a compressible flowIn the case of bodies, e.g. supercritical CO2Applying a force at one point in the system does not result in an immediate rise in pressure elsewhere in the system. Instead, the fluid proximate the application of force is compressed; that is, its density increases locally in response to the force. This compressed fluid then expands against the adjacent fluid particles, causing the adjacent fluid itself to compress. In many cases, the end result is the generation of pressure waves as a result of the movement of the locally dense fluid through the entire system.
In one or more embodiments of the above aspects, sample loss and cross-contamination are reduced by incorporating one or more devices that limit aerosolization (e.g., GLS). In one or more embodiments, the supercritical fluid chromatography system can further comprise a collector arm located downstream of the gas-liquid separator. In some embodiments, the supercritical fluid chromatography system includes a collector arm adapter (adapter) coupled to the collector arm. The collector arm adapter can be configured to further reduce aerosol when the combined flow stream is under atmospheric conditions. In some embodiments, the container stand is adjustable.
In some embodiments, the gas-liquid separator is made of stainless steel, a suitable polymer, or glass. In some embodiments, the back pressure regulator may be located upstream of the gas-liquid separator. In some embodiments, the compressible fluid is carbon dioxide (CO)2)。
The present technology also features methods of collecting a plurality of samples in Supercritical Fluid Chromatography (SFC). The method includes pumping a first flow stream comprising a compressible fluid and pumping a second flow stream comprising an incompressible fluid. The method further includes injecting the sample into the second flow stream, combining the first and second flow streams to form a combined flow stream, and then subjecting the flow stream to SFC conditions. The method further includes flowing the combined flow stream through a chromatography column and removing at least a portion of the compressible fluid from the combined flow stream, followed by collecting the sample in an open-bed XY-type collector.
In some embodiments, the compressible fluid used in the method is CO2. In some embodiments, aerosolization of the sample is prevented during collection of the sample in the open-bed XY collector.
The exemplary methods and apparatus of the present disclosure provide a number of advantages. For example, this technology significantly improves and expands the scope of SFC technology for use in various environments (settings), including the chemical industry and academic research laboratories. By eliminating various technical issues, such as cross-contamination, sample loss, and unsafe venting of compressed fluids, the present technology makes SFC a more robust and reliable method. Furthermore, the present technology makes SFC a more convenient method as it allows the use of standard open bed atmospheric XY type fraction collectors that have been used for other types of chromatography and are well known to those skilled in the art.
Drawings
The foregoing and other features and advantages provided by the present disclosure will be better understood by reference to the following description in conjunction with the accompanying drawings. The drawings are not necessarily to scale, emphasis instead generally being placed upon illustrating the principles of the technology.
FIG. 1 is a schematic of an SFC system having an open-bed XY-type collector, according to an exemplary embodiment of the present technique.
Fig. 2 shows a Waters fraction collector III ("WFCIII") apparatus, an XY type collector adapted for use with SFC instruments with a collector arm adapter and a gantry adapter installed, in accordance with an exemplary embodiment of the present technique.
FIG. 3A shows a collector arm adapter design on WFCIII according to an exemplary embodiment of the present technique.
Fig. 3B shows a schematic illustration of a collector arm adapter in accordance with an exemplary embodiment of the present technique.
FIG. 4 illustrates one embodiment of a stand adapter design on a WFCIII compatible with SFC instruments in accordance with an exemplary embodiment of the present technique.
FIG. 5 is a top view of a rack adapter design on a WFCIII compatible with SFC devices in accordance with exemplary embodiments of the present technique.
FIG. 6 is a schematic view of an embodiment of a gas-liquid separator useful in the present technology.
FIG. 7 shows a schematic diagram of an embodiment of a dripper for a gas-liquid separator of the present technology.
FIG. 8 shows another embodiment of a gas-liquid separator useful in the present technology.
Fig. 9 shows a schematic embodiment of an open bed atmospheric collection system.
Detailed Description
To prevent sample loss and cross-contamination when collecting fractions for SFC, the present technology utilizes a gas-liquid separator (GLS) installed into the flow stream after the BPR, with the purpose of venting most of the gaseous carbon dioxide (CO)2) Or any supercritical fluid used in the process, while retaining the incompressible modification liquid in which the sample is dissolved. Despite CO2May be a common supercritical fluid for SFC, but other suitable supercritical fluids may be nitrous oxide (N)2O), sulfur hexafluoride (SF)6) Or chlorofluorocarbons (CFCs), such as freon. One of ordinary skill in the art can vary the size, geometry, and operational settings of the GLS to optimize the GLS for flow rates on the order of several mils/min to several hundred milliliters/min.
The GLS described in international publication number WO 2010/056313 (the contents of which are incorporated herein by reference in their entirety) comprises a chamber in which a special conical tube of gradually increasing inner diameter is inserted. The end of the conical tube is angled so that as the gas-liquid mixture flows out of the conical tube and into the larger chamber, the flow is directed at an angle tangential to the impact wall of the separator to impact the inner wall of the chamber.
Since the gas-liquid flow does not go vertically downwards as it leaves the conical tube, coalescence (coalescence) of the modified liquid with the sample begins inside the GLS. The point of impact and the angle of impact serve to direct the liquid stream into a downward spiral path toward the liquid exit point. At the same time, compressible fluids such as CO2Is discharged upon exiting the conical tube. The modified liquid and sample are able to drain toward the bottom of the GLS due to controlled coalescence of the modified liquid and sample inside the GLS as the compressible fluid drains.
In embodiments, after passing through the GLS, the modifying liquid has been contacted with a compressible fluid such as CO2Separate and therefore no longer in danger of being aerosolized. The modified liquid now behaves like any other mobile phase fluid common to other types of chromatography (such as HPLC, MPLC, LPLC or Flash chromatography). Thus, it can be collected using standard open bed XY type fraction collectors known to those skilled in the art without concern for sample loss or cross contamination.
Some embodiments of the present technology further comprise a collector arm adapter (see, e.g., fig. 3A) that can be attached to the XY type collector arm, downstream of the GLS. The function of such collector arm adapters is to suppress and/or reduce aerosol generation once the fluid stream is subjected to atmospheric conditions (e.g., the position of the fluid stream as it leaves the collector tip of the mechanical arm). For example, if trace amounts of residual CO remain in the flow stream after passing through the GLS2(e.g., 0.001% -1%, 0.01% -0.1%) then the collector arm adapter is suitable. The collector arm adapter includes a cover (cover) that surrounds a tip (tip) that dispenses the sample to the collector rack. The collector arm adapter creates an enclosure (enclosure) to trap any remaining aerosol, which may be trace residual CO left in the incompressible fluid after the combined stream passes through the GLS2And then produced. By coupling the GLS to the collector arm adapter, aerosols can be substantially confined between the space where the stream exits the collector and the receptacle below the collector at a significantly reduced scaleWithin a very limited range around the fluid flow stream. In some embodiments, the aerosol is completely diminished and not observed in this design.
The method can include an adjustable receptacle stand that can be coupled to the GLS and the collector arm adapter. In addition to the adjustable height of the stand, the corresponding size and opening of the receiving port of the container stand can accommodate a wide range of fluid flow characteristics to ensure high collection efficiency of the distillate stream.
The present technique also includes an optimization method for hardware development of a characteristic SFC instrument. The method includes designing the GLS and collector arm adapter according to actual SFC flow characteristics to optimize the ability to control gas emissions and aerosol abatement to a maximum extent. The GLS may be made of stainless steel, polymer, glass, or other types of materials compatible with the process. The geometry and size of the GLS may be commensurate with the actual flow rate to ensure proper exhaust flow while maintaining the majority of the fluid flow downward into the collector. The collector arm adapter (see, e.g., fig. 3A and 3B) can include various sizes and geometries depending on flow rate and composition for optimized aerosol confinement and abatement capability. The rack adapter (see, e.g., fig. 4 and 5) may include a design for adjustable height and for receiving and connecting various types of containers (from, e.g., tubes, bottles, kettles to large glass bottles) to ensure maximum collection efficiency, encapsulated liquid flow, and minimum aerosol generation.
The present technology may also include optimization methods for method development. The process may include optimizing process parameters, such as pressure settings on the GLS, which may be on the order of a few psi to 50-60 bar, in combination with geometries and dimensions specifically tailored for optimal performance of gas-liquid separation and venting. The method further includes adjusting the collector arm adapter in terms of its size and spatial arrangement on the robotic arm for optimal aerosol control efficiency.
The present technology also includes various integrations of the use of the method and apparatus for fraction collection purposes. Such developments with XY-type collectors include, but are not limited to, routine fraction collection from high-efficiency SFC, secondary collection in addition to conventional fraction collection in SFC, fraction collection for high-flow, high-speed supercritical fluid flash chromatography, and any other type of pressurized liquid process where there is a potential risk of aerosol generation during collection.
One such embodiment of the above-described technique is shown in fig. 1, with fig. 1 showing a mass-directed SFC100 (MD-SFC 100) production system 100. The components of the system are interconnected by suitable conduits 101, the conduits 101 being capable of withstanding the extreme pressures and temperatures necessary to achieve supercritical conditions without corrosion or other safety issues. In one embodiment, the system comprises CO2Supply 105, followed by flow meter 106 to control CO through the system2And (4) flowing. There is also a separate reservoir 111 containing a modifier solvent, such as methanol. In some embodiments, there is a separate for the CO2And modifier solvent pumps 110, 115. In some embodiments, there is a Waters 2767 sample manager 120 (including sample injection 116 and open bed collector 160). There is also an in-line heater 125, a separation column 126 surrounded by a column furnace 127. In some embodiments, there is an adjustable distributor 128 that directs a portion of the stream to a mass spectrometer detector 135 and the remaining portion of the stream to a UV/PDA detector 130. In some embodiments, there is an automatic BPR 131 located downstream of the UV/PDA detector. There is a make-up pump 132 downstream of the BPR, and a heat exchanger 133. In some embodiments, GLS 140 is used to remove compressible fluids (e.g., 100% removal, 99.98% removal, 99.8% removal, 99% removal) from the combined flow stream and vent it without aerosolization and corresponding sample loss and cross-contamination. After connection point 141, a portion of the stream is directed to waste vessel 150, while the remaining stream is directed to fraction collector 160 (shown here as a Waters 2767 fraction collector) and Waters Fraction Collector (WFCIII) 155. In this configuration, a Waters Fraction Collector (WFCIII), XY type fraction collector, was integrated as the second collector. WFCIII is laterally perpendicular (plumb) to Waters 2767 fraction collector 160 and is controlled by Waters Masslynx software controlling the entire chromatography system 100. In one embodiment, Waters 2767 fraction collector 160 is the main fraction collector and is responsible for collecting the majority of the fraction. In one embodiment, the WFCIII may optionally be used as a secondary fraction collector 155. The purpose of the optional secondary collector 155 is to collect any fractions missed by the primary collector 160. For example, a fault or other unforeseen condition in the software may prevent the primary collector from collecting all of the fractions, and thus there may be a secondary collector to collect any uncollected fractions. Thus, in certain embodiments, only one fraction collector (e.g., Waters 2767 fraction collector 160) may be used, while in certain embodiments multiple fraction collectors may be used.
In other embodiments (not shown), the system 100 may be combined with other fluids for performing SFC. That is, other compressible fluids that can be processed to form a supercritical phase for chromatography can be used in place of CO2. For example, in one embodiment, nitrous oxide (N) may be used2O). Alternatively, in one embodiment, other compressible fluids may be used, such as sulfur hexafluoride (SF)6) Or chlorofluorocarbons (CFCs) such as freon.
Fig. 2 shows a WFCIII apparatus, which is an XY type collector mounted with a collector arm adapter 230 (e.g., collector arm adapter 305 of fig. 3A) and a gantry adapter 220 (e.g., gantry adapter 405 of fig. 4 and 505 of fig. 5) for an SFC instrument (e.g., part number 155 of fig. 1). In such embodiments, the collector operates according to standards set by instrumental methods from UV, mass spectrometry, and/or evaporative light scattering detectors ("ELSDs") and other signals to collect fractions of the compounds of interest. The WFCIII collector can be fully integrated and controlled by running software that controls the entire chromatography system. The WFCIII runs in a complementary fashion with the Waters 2767 collector to ensure higher collection efficiency, or the Waters 2767 collector acts as a stand-alone collector. WFCIII can be triggered by a line of injection (line of injection), a mass spectrum from the system, peak-based (peak-based) signals from UV, ELSD or any type of detector, or different types of algorithmic combinations of these signals, or it can collect fractions by time-windowing, time-division mode of peak triggering, or any other manual mode that can be controlled by preset methods. The configuration in this embodiment may ensure high collection efficiency and may reduce the risk of potential sample loss from random failures. This configuration can also enrich the multifunctional collection feature (feature) to further expand the applicability, robustness, economy and flexibility of SFC instruments for more chromatographic applications including but not limited to high throughput analysis and purification, chiral analysis, flash chromatography for drugs, natural products, food analysis, environmental monitoring, petroleum analysis and/or alternative energy development.
The collector arm adapter 305 of fig. 3A is an optional component. Without discharging all CO2Or the fluid may be compressed and a small portion retained, the adaptor arm 305 may prevent sample loss/cross-contamination by limiting the space around the exit tip.
Fig. 3B shows a schematic of the internal geometry of the collector arm adapter (i.e., adapter 305) depicted in fig. 3A. Fluid enters through inlet 355 and flows through outlet 360. Any aerosol resulting from this transfer is collected by the enclosure portion 365. In one embodiment, inlet portion 355 has a length of 8 millimeters. In one embodiment, the length of the outlet portion 360 is 6 millimeters. In one embodiment, the enclosure element 365 has a length of 14 millimeters.
While the collector arm adapter 305 is an optional element that may enhance performance, the GLS is a necessary component. GLS rejects a significant portion (e.g., 100%, 99%) of the CO from the combined flow stream2
The gas-liquid separator (e.g., GLS 140) used in the system of fig. 1 is shown in more detail in fig. 6. The separator includes an inlet flow port 650, a gas exhaust 655, a top cover 660, an outer vessel 670, a bottom cover 680, a liquid outlet port 685 and a drain port 690. A special conical tube with gradually increasing inner diameter, called a dripper, is inserted into the separator. The dripper nozzle 667, through which the flow leaves the dripper to the separator, the outlet, is wider than the diameter of the dripper where the flow enters 666 (the inlet). The size of the drippers is optimized for the flow rate of the system, which helps to merge the aerosol into a uniform (unified) flow. Typically, the ratio of the outlet diameter to the inlet diameter is 2-100 to 1. The ratio of the outlet diameter to the inlet diameter is about 2-4 to 1, preferably about 3 to 1, for flow rates up to about 100 grams/minute. This ratio can be adjusted to accommodate flow rates up to 1000 grams/minute.
The dripper shown in fig. 7, e.g. dripper 665 of fig. 6, has an angle of 10 to 80 degrees with respect to the downward-directed vertical axis of the separator. In other words, the outlet of the dripper is neither straight downwards nor directly sideways, but is interposed between the two. The angle is in the vertical direction and is not a chamfer.
Another embodiment of GLS is shown in fig. 8. A feed stream is introduced into the GLS through input port 805. As the fluid passes through the dripper 810, it exits through the dripper nozzle 815. The incompressible fluid collects on the inner wall 820 and falls under gravity towards the sump 825 and eventually flows through the outlet 830. At the same time, the compressible fluid escapes through the gas vent 835.
The GLS may be located anywhere downstream of the BPR, most effectively upstream of the fraction collector. In the embodiment shown in fig. 1, the GLS is located after the heat exchanger. In another embodiment, multiple gas-liquid separators may be located after connection point 141.
Fig. 9 shows a schematic embodiment of an open bed atmospheric collection system. Showing the collector arm adapter operating in combination with the rack adapter to deliver the sample to the receptacle. The fluid flows through GLS 905 (i.e., GLS 140 in fig. 1). After a portion of the sample is collected by the main fraction collector 910 (i.e., the Waters 2767 fraction collector 160 from fig. 1), a portion of the sample passes through the collector arm adapter 920, i.e., the component 305 shown in fig. 3A. Any remaining trace aerosols are collected by the rack adapter 930 (i.e., component 220 in fig. 2, component 405 in fig. 4, and component 505 in fig. 5). The fraction then enters vessel 940.
The techniques described above can be adapted for XY type fraction collectors without Z-motion (e.g., motion in the vertical direction) for the preparation of SFC applications. The technology can modify the existing XY fraction collector without Z-direction movement, so that the collector meets the requirements of technology and use safety in the SFC system. Aerosol can create safety issues when generated outside of the SFC system. Furthermore, by reducing the presence of aerosols, the present techniques significantly reduce sample loss and cross-contamination when collecting fractions.
The present technology significantly improves and expands the scope of SFC technology for use in a variety of environments, including the chemical industry and academic research laboratories. By eliminating various technical issues such as cross-contamination, sample loss, and unsafe venting of compressed fluids, the present technology makes SFC a more robust and reliable method. Furthermore, the present technology makes SFC a more convenient method as it allows the use of standard open bed atmospheric XY type fraction collectors that have been used for other types of chromatography and are well known to those skilled in the art.
The present technique can be used in any process where there is a risk of generating unwanted aerosols. The flow conditions of the system can be optimized to cut down on aerosols generated by depressurization of the pressurized fluid to ensure collection efficiency and safe operation under atmospheric conditions.
While various aspects of the disclosed apparatus and methods have been shown and described, modifications may occur to those skilled in the art upon reading the specification. The present application includes such variations.

Claims (11)

1. A supercritical fluid chromatography system comprising:
a first pump for pumping a first flow stream comprising a compressible fluid;
a second pump for pumping a second flow stream comprising modifier fluid, the second pump being in parallel with the first pump;
a column located in a combined flow stream, the column located downstream of the first pump and the second pump, the combined flow stream comprising the first flow stream, the second flow stream, and the sample;
a detector located downstream of the column;
a gas-liquid separator downstream of the detector, the gas-liquid separator configured to discharge a majority of the compressible fluid while retaining a majority of the sample to avoid sample loss and cross-contamination; and
an open-bed XY-type collector located after the gas-liquid separator.
2. The supercritical fluid chromatography system of claim 1 further comprising a collector arm located downstream of said gas-liquid separator.
3. The supercritical fluid chromatography system of claim 2, further comprising a collector arm adapter coupled to the collector arm, the collector arm adapter configured to reduce aerosols when the combined flow stream is at atmospheric conditions.
4. The supercritical fluid chromatography system of claim 1 further comprising an adjustable container stand coupled to the XY type collector.
5. The supercritical fluid chromatography system of claim 1, wherein the gas-liquid separator is made of stainless steel, polymer, or glass.
6. The supercritical fluid chromatography system of claim 1 further comprising a back pressure regulator located upstream of said gas-liquid separator.
7. The supercritical fluid chromatography system of claim 1, wherein the compressible fluid is carbon dioxide (CO)2)。
8. A method for collecting a plurality of samples in Supercritical Fluid Chromatography (SFC), the method comprising:
pumping a first flow stream comprising a compressible fluid;
pumping a second flow stream comprising an incompressible fluid;
injecting the sample into the second flow stream;
combining the first flow stream and the second flow stream to form a combined flow stream;
subjecting the flow stream to SFC conditions;
flowing the combined flow stream through a chromatography column;
removing at least a portion of said compressible fluid from the combined flow stream; and
the samples were collected in an open-bed XY type collector.
9. The method of claim 8, wherein the compressible fluid is CO2
10. The method of claim 8, wherein aerosolization of the sample is prevented during collection of the sample in the open-bed XY collector.
11. The method of claim 8, wherein removing at least a portion of the compressible fluid from the combined flow stream comprises removing at least 99% of the compressible fluid.
HK14106703.9A 2011-06-17 2012-06-15 Methods and devices for open-bed atmospheric collection for supercritical fluid chromatography HK1193068B (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US61/498458 2011-06-17

Publications (2)

Publication Number Publication Date
HK1193068A true HK1193068A (en) 2014-09-12
HK1193068B HK1193068B (en) 2018-01-19

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