WO2018022958A1 - Procédé et appareil pour ajuster la pression moyenne de colonne dans un système de chromatographie pour approcher une pression moyenne de colonne identifiée - Google Patents

Procédé et appareil pour ajuster la pression moyenne de colonne dans un système de chromatographie pour approcher une pression moyenne de colonne identifiée Download PDF

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Publication number
WO2018022958A1
WO2018022958A1 PCT/US2017/044291 US2017044291W WO2018022958A1 WO 2018022958 A1 WO2018022958 A1 WO 2018022958A1 US 2017044291 W US2017044291 W US 2017044291W WO 2018022958 A1 WO2018022958 A1 WO 2018022958A1
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Prior art keywords
chromatographic system
carbon dioxide
dioxide based
based separation
column pressure
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PCT/US2017/044291
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English (en)
Inventor
Michael O. FOGWILL
Jason F. Hill
Joseph D. Michienzi
Joshua A. SHREVE
Abhijit TARAFDER
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Waters Technologies Corporation
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Publication of WO2018022958A1 publication Critical patent/WO2018022958A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
    • B01D15/08—Selective adsorption, e.g. chromatography
    • B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
    • B01D15/16—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the conditioning of the fluid carrier
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
    • B01D15/08—Selective adsorption, e.g. chromatography
    • B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
    • B01D15/40—Selective adsorption, e.g. chromatography characterised by the separation mechanism using supercritical fluid as mobile phase or eluent

Definitions

  • the present disclosure relates to supercritical fluid chromatography (SFC) and/or a carbon dioxide based chromatography system. More specifically, the present disclosure relates to methods and systems for controlling the density of the mobile phase in the region of interest of a chromatographic system.
  • SFC supercritical fluid chromatography
  • carbon dioxide based chromatography system More specifically, the present disclosure relates to methods and systems for controlling the density of the mobile phase in the region of interest of a chromatographic system.
  • chromatographic system e.g., carbon dioxide based chromatography, SFC, high pressure liquid chromatography (HPLC), gas chromatography (GC)
  • HPLC high pressure liquid chromatography
  • GC gas chromatography
  • WO2014/201222 Al researchers at Waters Technologies Corporation disclosed a methodology for scaling SFC and/or carbon dioxide based chromatography methods between different systems and/or column configurations.
  • the methodology includes measuring an average mobile phase density from the density profile along the system during a first separation utilizing carbon dioxide as a mobile phase component and substantially duplicating the average density for a second separation to produce similar selectivity and retention factors.
  • the researchers at Waters Technologies Corporation also disclosed that the average of the pressure profile may be used as a close approximation to duplicate average of the density profiles between separations.
  • WO2015/023533 Al researchers at Waters Technologies Corporation disclosed apparatus for regulating the average mobile phase density or pressure in a carbon dioxide based chromatographic system.
  • the disclosed apparatus includes a controller, a set of pressure or density sensors and a set of instructions capable of determining the pressure drop across a column and adjusting at least one system component or parameter to achieve a predetermined average mobile phase density or pressure in the system.
  • researchers at Waters Technologies Corporation have discovered specific new ways to efficiently transfer a carbon dioxide based separation procedure from a first chromatographic system to a second system.
  • the present disclosure relates to methods and systems for efficiently transferring a carbon dioxide based separation procedure from a first chromatographic system to a second chromatographic system.
  • the methods involve identifying an average column pressure for the carbon dioxide based separation in the first chromatographic system;
  • determining a measured average column pressure for the carbon dioxide based separation in the second chromatographic system comprises calculating the measured average column pressure from a plurality of measurements proximate to the column in the second chromatographic system. In some embodiments, determining a measured average column pressure for the carbon dioxide based separation in the second chromatographic system comprises calculating the measured average column pressure from a plurality of measurements at the column in the second chromatographic system.
  • the method involves altering the flow rate of the mobile phase for the carbon dioxide based separation in the second chromatographic system to more closely match the identified average column pressure for the carbon dioxide based separation in the first chromatographic system.
  • Altering the flow rate may comprise increasing the flow rate of the mobile phase for the carbon dioxide based separation in the second chromatographic system to increase the measured average column pressure in the second chromatographic system.
  • Altering the flow rate may comprise decreasing the flow rate of the mobile phase for the carbon dioxide based separation in the second
  • Some embodiments involve repeating the steps of determining a measured average column pressure for the carbon dioxide based separation in the second
  • Some embodiments involve, iteratively or continually, repeatedly altering the flow rate of the mobile phase for the carbon dioxide based separation in the second chromatographic system until the measured average column pressure for the carbon dioxide based separation in the second chromatographic system substantially matches the identified average column pressure for the carbon dioxide based separation in the first chromatographic system.
  • the method further includes continually measuring the average column pressure over a composition-programmed gradient separation of the first chromatographic system and altering the flow rate of the second chromatographic system to substantially match the average column pressure at any point along the composition- programmed gradient separation of the second chromatographic system.
  • the method involves altering the composition of the mobile phase for the carbon dioxide based separation in the second chromatographic system to more closely match the identified average column pressure for the carbon dioxide based separation in the first chromatographic system.
  • Altering the composition of the mobile phase for the carbon dioxide based separation in the second chromatographic system may comprise selecting a co-solvent to adjust (i.e., modify) the viscosity of the mobile phase in the second chromatographic system.
  • Altering the composition of the mobile phase for the carbon dioxide based separation in the second chromatographic system may comprise adding a co-solvent to increase the average column pressure of the carbon dioxide based separation in the second chromatographic system by increasing the viscosity of the mobile phase. Altering the composition of the mobile phase for the carbon dioxide based separation in the second chromatographic system comprises adding a co-solvent to decrease the average column pressure of the carbon dioxide based separation in the second chromatographic system by decreasing the viscosity of the mobile phase.
  • Altering the composition of the mobile phase for the carbon dioxide based separation may comprise altering a portion of a cosolvent in the mobile phase in the second chromatographic system to adjust the viscosity of the mobile phase in the second chromatographic system to more closely match the identified average column pressure for the carbon dioxide based separation in the first chromatographic system.
  • Some embodiments involve repeating the steps of determining a measured average column pressure for the carbon dioxide based separation in the second
  • Some embodiments involve, iteratively or continually, repeatedly altering the composition of the mobile phase for the carbon dioxide based separation in the second chromatographic system until the measured average column pressure for the carbon dioxide based separation in the second chromatographic system substantially matches the identified average column pressure for the carbon dioxide based separation in the first chromatographic system.
  • composition of the mobile phase for the carbon dioxide based separation may be altered downstream of the column in the second chromatographic system. Such alteration may comprise adding a co-solvent into a flow downstream of the column.
  • the method further includes continually measuring the average column pressure over a composition-programmed gradient separation of the first chromatographic system and altering the flow rate of the second chromatographic system to substantially match the average column pressure at any point along the composition- programmed gradient separation of the second chromatographic system.
  • the method involves adding a restrictive element between the inlet of a first column downstream of the sample introduction and the inlet of the back pressure regulator downstream of the column in the second chromatographic system to more closely match the identified average column pressure for the carbon dioxide based separation in the first chromatographic system. More preferably the restrictive element may be added between the inlet of the first column and the inlet of the detector. The restrictive element may be added between an outlet of the first column and an inlet of a second column downstream of the sample introduction in the second chromatographic system. The restrictive element may be added between the outlet of the first column and the inlet of the detector in the second chromatographic system.
  • Some embodiments involve repeating the steps of determining a measured average column pressure for the carbon dioxide based separation in the second
  • Some such embodiments involve replacing a restrictive element between the inlet of a first column downstream of the sample introduction and the inlet of the back pressure regulator downstream of the column in the second chromatographic system to more closely match the identified average column pressure for the carbon dioxide based separation in the first chromatographic system. Some embodiments involve replacing a restrictive element between the inlet of a first column downstream of the sample introduction and the inlet of the detector downstream of the column in the second chromatographic system until the measured average column pressure for the carbon dioxide based separation in the second
  • chromatographic system substantially matches the identified average column pressure for the carbon dioxide based separation in the first chromatographic system.
  • the method further includes continually measuring the average column pressure over a composition-programmed gradient separation of the first chromatographic system and altering the flow rate of the second chromatographic system to substantially match the average column pressure at any point along the composition- programmed gradient separation of the second chromatographic system.
  • methods of the present disclosure may involve any combination of (a) altering the flow rate of the mobile phase for the carbon dioxide based separation in the second chromatographic system; (b) altering the composition of the mobile phase for the carbon dioxide based separation in the second chromatographic system; and/or (c) adding a restrictive element between the inlet of a first column downstream of the sample introduction and the inlet of the back pressure regulator downstream of the column in the second chromatographic system.
  • methods of the present disclosure may involve disclosed variations of any combination of the foregoing steps.
  • FIGS. 1A, IB, and 1C illustrate the effect of different columns and back pressure regulator (BPR) set points on average column pressure in chromatography systems.
  • FIG. 2A illustrates a method, using flow rates, for efficiently transferring a carbon dioxide based separation from a first chromatographic system in accordance with embodiments of the invention.
  • FIG. 2B illustrates the effect of different mobile phase flow rates on average column pressure in a chromatography system in accordance with embodiments of the invention.
  • FIG. 3A illustrates a method, using mobile phase composition, for efficiently transferring a carbon dioxide based separation from a first chromatographic system in accordance with embodiments of the invention.
  • FIG. 3B illustrates the effect of different mobile phase compositions on average column pressure in a chromatography system in accordance with embodiments of the invention.
  • FIG. 4 illustrates a chromatography system in accordance with embodiments of the invention in which the mobile phase composition may be altered downstream of the outlet of the column.
  • FIG. 5A illustrates a method, using a restrictive element, for efficiently transferring a carbon dioxide based separation from a first chromatographic system in accordance with embodiments of the invention.
  • FIG. 5B illustrates a chromatography system in accordance with embodiments of the invention in which a restrictive element may be selected between an outlet of a first column and an inlet of a second downstream column.
  • FIG. 6 illustrates a chromatography system in accordance with embodiments of the invention in which a restrictive element may be selected between an outlet of a column and an inlet of a downstream detector.
  • chromatographic system refers to a combination of instruments or equipment, e.g., a pump, a column, a detector, and accompanying accessories that may be used to perform a separation to detect target analytes.
  • the present disclosure relates to carbon dioxide based separation in a chromatographic system having a pump, a column located downstream of the pump, a detector located downstream of the column, a back pressure regulator located downstream of the detector, and a first sensor and a second sensor.
  • a chromatographic system having a pump, a column located downstream of the pump, a detector located downstream of the column, a back pressure regulator located downstream of the detector, and a first sensor and a second sensor.
  • the sensors may be pressure sensors for measuring mobile phase pressure in the system.
  • Mobile phase pressure measurements may be used, along with measured or estimated mobile phase temperatures, to estimate the mobile phase density.
  • the first sensor may be contained in or connected to an outlet of a pump, may be contained in or connected to an inlet of a column, or positioned anywhere in between.
  • the second sensor may be contained in or connected to an inlet of a back pressure regulator, may be contained in or connected to an outlet of the column, or positioned anywhere in between.
  • the mobile phase density or pressure in the system may be at equilibrium when the first and second mobile phase density or pressure measurements are measured by the first and second sensors, or when the flow rate or composition is altered or the restrictive element is added or replaced.
  • the mobile phase density or pressure in the system is not at equilibrium when the first and second mobile phase density or pressure measurements are measured by the first and second sensors, or when the flow rate or composition is altered or the restrictive element is added or replaced.
  • the present disclosure relates to carbon dioxide based separation in a chromatographic system having a controller, a first sensor and a second sensor both in signal communication with the controller, and a set of instructions utilized by the controller.
  • the controller is capable of averaging the first and the second mobile phase pressure measurements to determine a measured average mobile phase pressure value.
  • the controller is capable of determining a measured average column pressure from the measured mobile phase pressure values.
  • the measured average mobile phase pressure value determined by the controller is a measured average column pressure or at least a close approximation thereof. In some such
  • the controller is capable of comparing the measured average column pressure value with an identified average column pressure. In some such embodiments, the controller is capable of altering a flow rate or composition of the mobile phase to more closely match an identified average column pressure. In some such embodiments, the controller suggests an restrictive element to be added or replaced to more closely match an identified average column pressure.
  • the present disclosure may be useful for transferring separations between analytical scale chromatographic systems, preparative scale chromatographic systems, and combinations thereof.
  • the present disclosure may be useful in transferring a separation from an analytical scale chromatographic system to a preparative scale
  • Chromatographic systems for which the present disclosure may be applicable may comprise UPC and/or SFC columns including both chiral and achiral stationary phases.
  • the distinction between different chromatographic systems may include any change in the system configuration that results in a change in the overall operating average mobile phase density or average column pressure.
  • the distinction between different chromatographic systems may be the use of different instruments such as a carbon dioxide based analytical chromatography system, for example a system commercially available from Waters Technologies Corporation (Milford, MA) and branded as an ACQUITY® UPC 2 system versus a carbon dioxide based preparative chromatography system, for example a system commercially available from Waters Technologies Corporation (Milford, MA) and branded as a Prep 100 SFC system.
  • the distinction may also be a change in one or more components on the same instrument, e.g., a change in system configuration.
  • the distinction may be a change in column configuration, e.g. length, internal diameter or particle size, or a change in tubing, e.g., length or internal diameter, a change in a valve, e.g., the addition or removal of a valve, or the addition or removal of system components such as detectors, column ovens, etc..
  • the present disclosure may be applied to any change or distinction, e.g. instrument, column particle size, column length, etc., between different chromatographic systems which results in greater than about a 10% change in overall operating average mobile phase density or average column pressure. More preferably, the present disclosure may be applied to any change or distinction which results in greater than about a 5% change in overall operating average mobile phase density or average column pressure. Even more preferably, the present disclosure may be applied to any change or distinction which results in greater than about a 1% change in overall operating average mobile phase density or average column pressure.
  • any change or distinction e.g. instrument, column particle size, column length, etc.
  • the present disclosure relates to efficiently transferring carbon dioxide based separations between systems.
  • the phrase "efficiently transferring" of a carbon dioxide based separation refers to the concept of transferring a carbon dioxide based separation, methodology, or method parameters between chromatographic systems while maintaining the chromatographic integrity of the separation, e.g., preserving retention factors and selectivity of at least one target analyte, preferably two or more target analytes.
  • An efficiently transferred separation is one that substantially reproduces the chromatographic integrity of the separation obtained on the first chromatographic system on the second chromatographic system.
  • an efficiently transferred carbon dioxide based separation is one wherein the second carbon dioxide based separation performed on the second chromatographic system has a target analyte, or target analytes, having substantially the same retention factor (k') or selectivity as the first carbon dioxide based separation performed on the first system.
  • the term “retention factor” or “k”' refers to the ratio of time an analyte is retained in the stationary phase to the time it is retained in the mobile phase under either isocratic or gradient conditions.
  • the difference in retention factor for any given target analyte between a first and a second separation should be minimized.
  • the difference in retention factor for a target analyte between a first and a second separation is less than about 10%. More preferably, the difference in retention factor for a target analyte between a first and a second separation is less than about 5%. Even more preferably, the difference in retention factor for a target analyte between a first and a second separation is less than about 1%.
  • the difference in retention factor for each target analyte, respectively, between a first and a second separation should also be minimized.
  • Multiple target analytes may include 2 or more target analytes, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.
  • all or a majority of the target analytes have substantially the same retention factor between the first and second separations. Because all analytes respond differently to system changes, not all of the target analytes may have substantially the same retention factor between the first and second separations.
  • the difference in retention factor for each multiple target analyte, respectively, between a first and a second separation is less than about 10%.
  • the difference in retention factor for each multiple target analyte, respectively, between a first and a second separation is less than about 5%. Even more preferably, the difference in retention factors for each multiple target analyte, respectively, between a first and a second separation is less than about 1%.
  • the term "selectivity" or “selectivity factor” or “a” refers to the degree of separation of two analytes in a separation.
  • the selectivity between two target analytes between a first and a second separation should be maintained.
  • the change in selectivity for two target analytes between a first and a second separation is less than about 10%. More preferably, the change in selectivity for two target analytes between a first and a second separation is less than about 5%. Even more preferably, the change in selectivity for two target analytes between a first and a second separation is less than about 1%.
  • carbon dioxide based separation and “carbon dioxide based separation procedure” refer to method parameters and/or settings used with a particular carbon dioxide based chromatographic system to control or effect a separation of target analytes.
  • the mobile phase in a carbon dioxide based separation includes at least, in part, carbon dioxide.
  • FIG. 1A illustrates a chromatographic system 100 featuring a pump 110, a column 120, a detector 130, and a post-detector back pressure regulator (BPR) 140.
  • BPR post-detector back pressure regulator
  • a sample is introduced into chromatographic system 100 of FIG. 1A upstream of the column.
  • FIG. 1A also includes a pressure diagram 160 that includes a line 162 that illustrates the pressure with respect to the system position.
  • the pressure diagram 160 of FIG. 1A also illustrates the set point ⁇ of the BPR 140 and the average column pressure P A -
  • FIG. IB illustrates a chromatographic system 150 featuring a pump 110, a column 125, a detector 130, and a post-detector BPR 140.
  • a sample is introduced into chromatographic system 150 of FIG. IB upstream of the column.
  • FIG. IB also includes a pressure diagram 160 that includes a line 164 that illustrates the pressure with respect to the system position.
  • the pressure diagram 160 of FIG. IB also illustrates the set point ⁇ of the BPR 140 and the average column pressure ⁇ .
  • FIG. IB share the BPR set point ⁇ . But chromatographic system 100 and chromatographic system 150 differ in that the particle diameter of their respective columns. The particle diameter of column 125 of FIG. IB is greater than that of column 120 of FIG. 1A.
  • Columns differences between chromatographic system are not limited to differences in particle diameter.
  • Column stationary phases may differ in regard to chemistry, base particle, ligand, bonding density, endcapping, pore size, etc.
  • Column manufacturers typically produce columns having the same stationary phase, e.g., same chemistry, same base particle, same ligand, same bonding density, same endcapping and same pore size, in several different particle size and column dimension configurations.
  • the two different separation systems have a first and a second respective column, wherein the first and second columns have similar stationary phases.
  • the similar stationary phases may have, at least, same chemistry, same base particle, same ligand, same bonding density, same endcapping or same pore size.
  • the present invention is applicable where similar stationary phases have the same chemistry.
  • the pressure diagrams 160 of FIGS. 1A and IB illustrate an effect of the difference in the column particle diameter between the two chromatographic systems 100 and 150.
  • FIGS. 1A and IB share the BPR set point P X
  • lines 162 and 164 illustrates that the smaller particle diameter produces a greater pressure drop across column 120 than the greater particle diameter produces across column 125.
  • the greater column particle diameter in column 125 produces a lesser pressure drop than the smaller particle diameter produces across column 120.
  • the average column pressure P A of the carbon dioxide based separation in the chromatographic system 100 of FIG. 1A is greater than the average column pressure P B of the carbon dioxide based separation in the chromatographic system 150 of FIG. IB .
  • FIG. 1C illustrates a chromatographic system 175 featuring a pump 110, a column 125, a detector 130, and a post-detector BPR 145.
  • BPR 145 of FIG. 1C may be the same as BPR 140 of FIGS. 1A and IB.
  • a sample is introduced into chromatographic system 175 of FIG. 1C upstream of the column.
  • FIG. 1C also includes a pressure diagram 160 that includes a line 166 that illustrates the pressure with respect to the system position.
  • the pressure diagram 160 of FIG. 1C also illustrates the set point Pz of the BPR 145 and the average column pressure Pc.
  • FIG. 1C illustrates that chromatographic system 175 uses a different set point for its BPR (i.e., Pz) than that used in FIGS. 1A and IB (i.e., P x ).
  • the set point of the BPR has been selected to address the difference between the column particle diameter.
  • the set point of BPR 145 in FIG. 1C is greater than that of BPR 140 of FIG. IB (i.e., P z > ⁇ ).
  • the set point of BPR 145 produces a greater average column pressure in chromatographic system 175 as compared to chromatographic system 150.
  • the average column pressure Pc of FIG. 1C is substantially the same as the average column pressure P A of FIG. 1A (i.e., Pz ⁇ ⁇ ).
  • the retention characteristics of analytes in the separation of FIG. 1A would be expected to substantially match those in the separation of FIG. 1C.
  • the inventors of the present disclosure recognized that, using average pressure as a close approximation for average density, the effect of mobile phase density on solubility and analyte retention can be normalized by substantially duplicating the average column pressure from a separation method in a first chromatographic system in a separation method in a second chromatographic system.
  • the inventors were aware that settings related to the post-detector back pressure regulator (BPR) may be changed to substantially match an average column pressure in another chromatographic system. But the inventors recognized that an average column pressure may be achieved in different SFC and/or a carbon dioxide based chromatographic systems without changing the settings related to post-detector BPR.
  • FIG. 2A illustrates a method 202 for efficiently transferring a carbon dioxide based separation procedure from a first
  • step 212 of FIG. 2A an average column pressure for a separation in a first chromatographic system is identified.
  • the identified average column pressure will be that for successful carbon dioxide based separation on the first
  • This average column pressure may be known and therefore readily available for identification. For example, where its separation is successful, the average column pressure ⁇ for chromatographic system 100 of FIG. 1A may be identified by mere reference to the known value. To the extent that the average column pressure for a successful separation in the first chromatographic system is not known, the column pressure in the first system may be measured (e.g., by one or more sensors) and its average may be determined in step 212.
  • Step 222 of FIG. 2A involves a second chromatographic system.
  • the second chromatographic system in step 222 differs from the first chromatographic system in step 212.
  • FIG. 2B illustrates a chromatographic system 200 featuring pump 110, column 125, detector 130, and post-detector BPR 140— similar to FIG. IB.
  • a sample is introduced into chromatographic system 200 of FIG. 2B upstream of the column.
  • Chromatographic system 200 of FIG. 2B which features the same column 125 as the system of FIG. IB, may be the second chromatographic system of step 222.
  • chromatographic system 100 differ in the particle diameter in their respective columns.
  • the particle diameter of column 125 of FIG. 2B is greater than that of column 120 of FIG. 1 A.
  • the difference in the column particle diameters results in a change in the overall operating average mobile phase density of average column pressure.
  • a measured average column pressure for a separation in a second chromatographic system is determined.
  • Step 222 involves averaging a plurality of measurements.
  • measurements may be taken between the outlet of pump 110 and the inlet of column 125 and between the outlet of column 125 and the inlet of BPR 140.
  • measurements are taken at the outlet of pump 110 and at the inlet of BPR 140.
  • measurements are taken at the inlet of column 125 and at the inlet of BPR 140.
  • measurements are taken at the inlet and outlet of column 125.
  • Pressure diagram 260 of FIG. 2B illustrates pressure with respect to system position for two different flow rates. As pressure diagram 260 illustrates, the pressure in a typical chromatographic system predominately drops between the inlet and the outlet of the column. In step 222, pressure measurements may be taken at any point in the system included in line 264 or line 266 can be used to determine the average column pressure.
  • Line 264 in pressure diagram 260 of FIG. 2B illustrates pressure with respect to system position at mobile phase flow rate 1. Any of the points along line 264 may represent measurements. Because flow rate 1 is the flow rate applied to column 125 in FIG. IB, lines 164 and 264 illustrates the same pressure drop across column 125. Based on line 264, pressure diagram 260 of FIG. 2B illustrates that flow rate 1 produces an average column pressure P B for system 200. Due to the similarities between system 150 and system 200, pressure diagram 260 indicates that flow rate 1 produces the same average column pressure P B as illustrated in FIG. IB.
  • the measured average column pressure for carbon dioxide based separation in a second chromatographic system is compared to the identified average column pressure for carbon dioxide based separation in the first chromatographic system. Due to the smaller particle diameter of column 120, the average column pressure P A of the carbon dioxide based separation in the chromatographic system 100 of FIG. 1A is greater than the average column pressure P B . In other words, the average column pressure P B for separation at flow rate 1 in system 200 is less than the average column pressure P A for separation in system 100 of FIG. 1A. In a typical first comparison, the average column pressures do not substantially match and the difference would not be acceptable. For the purpose of this disclosure, we presume that the difference between the average column pressures P A and P B is not acceptable.
  • step 242 of FIG. 2A the flow rate of the mobile phase for the carbon dioxide based separation in the second chromatographic system is altered to more closely match the identified average column pressure for carbon dioxide based separation in the first chromatographic system.
  • the inventors recognized that increasing the mobile phase flow rate will increase the pressure between the outlet of the pump and the inlet of the column whereas decreasing the flow rate will decrease that pressure.
  • the BPR set point represents the lower limit of the column pressure.
  • Measurements used to determine the average column pressure in the second chromatographic system represented by at least two points on line 264 of FIG. 2B, also provide information that is useful in selecting a new flow rate.
  • the pressure at the outlet of the column of the second system may not change significantly, or at all, as a result of altering the flow rate. Accordingly, although it may affect the pressure between the outlet of the pump and the inlet of the column and between the outlet of the column and the BPR inlet to a lesser degree, the inventors recognized that the mobile phase flow rate will chiefly affect the pressure between the inlet and the outlet of the column. Armed with this understanding, the flow rate of the mobile phase for the carbon dioxide based separation in the second chromatographic system can be readily altered to more closely match the identified average column pressure for carbon dioxide based separation in the first chromatographic system.
  • step 242 of FIG. 2A the flow rate of system 200 is altered to address the difference between the average column pressure P A of the carbon dioxide based separation in the chromatographic system 100 of FIG. 1 A and the average column pressure P B in system 200 of FIG. 2B, which is caused by the difference in the column particle diameters.
  • flow rate 1 is altered to higher, flow rate 2 because the average column pressure P B for separation at flow rate 1 in system 200 is less than the identified average column pressure P A for separation in system 100.
  • Pressure diagram 260 of FIG. 2B illustrates the effect of different flow rates on the pressure characteristics of chromatographic system 200 in accordance with
  • Pressure diagram 260 of FIG. 2B includes lines 264, 266 that illustrates the pressure with respect to system position at different flow rates. Pressure diagram 260 of FIG. 2B also illustrates a single BPR set point ⁇ for both flow rates. The chromatographic systems of FIGS. 1A, IB, and 2B share BPR set point ⁇ .
  • method 202 may further include determining a new measured average column pressure in step 222 after altering the flow rate in step 242.
  • Line 266 in pressure diagram 260 of FIG. 2B illustrates pressure with respect to system position at mobile phase flow rate 2. Any of the points along line 266 may represent column pressure measurements for flow rate 2. Based on line 266, pressure diagram 260 of FIG. 2B illustrates that flow rate 2 produces an average column pressure P FR2 for system 200.
  • a comparison of lines 266 and 264 illustrates that flow rate 2 (line 266) produces a greater pressure at the outlet of pump 110 than flow rate 1 (line 264).
  • the comparison of lines 266 and 264 also illustrates that flow rate 2 (line 266) produces a greater pressure drop across column 125 as compared to flow rate 1 (line 264).
  • the average column pressure P FR2 produced by flow rate 2 is greater than the average column pressure P B produced by flow rate 1.
  • FIG. 2B illustrates that increasing the mobile phase flow rate increases the average column pressure.
  • FIG. 2B also illustrates that decreasing the mobile phase flow rate decreases the average column pressure.
  • method 202 may further include comparing the new measured average column pressure to the identified average column pressure in step 232 after altering the flow rate in step 242.
  • the average column pressure P FR2 produced by flow rate 2 in system 200 of FIG. 2B is closer to the identified average column pressure P A than the average column pressure P B produced by flow rate 1.
  • FIG. 2B illustrates that the mobile phase flow rate can be altered to more closely match a target average column pressure in a chromatography system.
  • the average column pressure P FR2 produced by flow rate 2 in system 200 of FIG. 2B substantially matches the average column pressure P A of FIG. 1A. Accordingly, by altering the flow rate as illustrated in FIG. 2B, even without adjusting the BPR set point, the average column pressure of a first chromatographic system can be substantially matched by the average column pressure in the second chromatographic system. Thus, the retention characteristics of analytes in the separation of FIG. 1A would be expected to substantially match those in the separation of FIG. 2B.
  • Method 202 may further include continually measuring the average column pressure over a composition-programmed gradient separation of the first chromatographic system and altering the flow rate of the second chromatographic system to substantially match the average column pressure at any point along the composition-programmed gradient separation of the second chromatographic system.
  • the gradient slope in the second chromatographic system 200 may not be the same as the first system.
  • Conventional method transfer techniques may be employed to transfer the gradient method between systems.
  • composition of the mobile phase can be used to change the pressure characteristics of a chromatographic system.
  • composition of the mobile phase can be used to adjust the average column pressure in a chromatographic system.
  • FIG. 3A illustrates a method 302 for efficiently transferring a carbon dioxide based separation procedure from a first chromatographic systems to a second
  • step 312 of FIG. 3A an average column pressure for a separation in a first chromatographic system is identified.
  • Step 312 is similar to step 212, and the variations described above with respect to FIG. 2A apply.
  • the average column pressure P A for the successful separation in first chromatographic system 100 of FIG. 1A is again identified by mere reference to the know value.
  • step 322 of FIG. 3 A involves a second
  • FIG. 3B illustrates a chromatographic system 300 featuring pump 110, column 125, detector 130, and post-detector BPR 140— similar to FIG. IB.
  • a sample is introduced into chromatographic system 300 of FIG. 3B upstream of the column.
  • Chromatographic system 300 of FIG. 3B which features the same column 125 as the system of FIG. IB, may be the second chromatographic system of step 322.
  • Chromatographic system 300 and chromatographic system 100 differ in the particle diameter in their respective columns.
  • the particle diameter of column 125 of FIG. 3B is greater than that of column 120 of FIG. 1A.
  • the difference in the column particle diameters results in a change in the overall operating average mobile phase density of average column pressure.
  • step 322 of FIG. 3 A a measured average column pressure for a separation in a second chromatographic system 300 is determined.
  • Step 322 is similar to step 222, and the variations described above with respect to FIG. 2A apply.
  • Line 364 in pressure diagram 360 of FIG. 3B illustrates pressure with respect to system position using mobile phase composition 1. Any of the points along line 364 may represent measurements. Because composition 1 is the composition applied to column 125 in FIG. IB, lines 164 and 364 illustrates the same pressure drop across column 125. Based on line 364, pressure diagram 360 of FIG. 3B illustrates that composition 1 produces an average column pressure P B for system 300. Due to the similarities between system 150 and system 300, pressure diagram 360 indicates that composition 1 produces the same average column pressure P B as illustrated in FIG. IB.
  • step 332 of FIG. 3A involves comparing the measured average column pressure for carbon dioxide based separation in the second chromatographic system with the identified average column pressure for carbon dioxide based separation in the first chromatographic system. Due to the smaller particle diameter of column 120, the average column pressure P A of the carbon dioxide based separation in the chromatographic system 100 of FIG. 1A is greater than the average column pressure P B . In other words, the average column pressure P B for separation with composition 1 in system 300 is less than the average column pressure P A for separation in system 100 of FIG. 1A. In a typical first comparison, the average column pressures do not substantially match and the difference would not be acceptable. For the purpose of this disclosure, we presume that the difference between the average column pressures P A and P B is not acceptable.
  • step 342 of FIG. 3A the composition of the mobile phase for the carbon dioxide based separation in the second chromatographic system is altered to more closely match the identified average column pressure for carbon dioxide based separation in the first chromatographic system.
  • the inventors recognized that a mobile phase with a more viscous composition will increase the pressure between the outlet of the pump and the inlet of the column whereas a less viscous composition will decrease that pressure.
  • the BPR set point represents the lower limit of the column pressure.
  • Measurements used to determine the average column pressure in the second chromatographic system represented by at least two points on line 364 of FIG. 3B, also provide information that is useful in selecting a new flow rate.
  • the pressure at the outlet of the column of the second system may not change significantly, or at all, as a result of altering the composition. Accordingly, although it may affect the pressure between the outlet of the pump and the inlet of the column and between the outlet of the column and the BPR inlet to a lesser degree, the inventors recognized that the mobile phase composition will chiefly affect the pressure between the inlet and the outlet of the column. Armed with this understanding, the composition of the mobile phase for the carbon dioxide based separation in the second chromatographic system can be readily altered to more closely match the identified average column pressure for carbon dioxide based separation in the first chromatographic system.
  • step 342 of FIG. 3A the composition of system 300 is altered to address the difference between the average column pressure P A of the carbon dioxide based separation in the chromatographic system 100 of FIG. 1 A and the average column pressure P B in system 300 of FIG. 3B, which is caused by the difference in the column particle diameters.
  • composition 1 is altered to higher- viscosity, composition 2 because the average column pressure P B for separation at flow rate 1 in system 300 is less than the identified average column pressure P A for separation in system 100.
  • Pressure diagram 360 of FIG. 3B illustrates the effect of different mobile phase compositions on the pressure characteristics of chromatographic system 300 in accordance with embodiments of the invention.
  • Pressure diagram 360 of FIG. 3B includes lines 364, 366 that illustrates the pressure with respect to system position with different mobile phase compositions.
  • Pressure diagram 360 of FIG. 3B also illustrates a single BPR set point ⁇ for both flow rates.
  • the chromatographic systems of FIGS. 1A, IB, and 3B share BPR set point ⁇ .
  • method 302 may further include determining a new measured average column pressure in step 322 after altering the flow rate in step 342.
  • Line 366 in pressure diagram 360 of FIG. 3B illustrates pressure with respect to system position at mobile phase composition 2. Any of the points along line 366 may represent column pressure measurements for composition 2. Based on line 366, pressure diagram 360 of FIG. 3B illustrates that composition 2 produces an average column pressure Pc 2 for system 300.
  • a comparison of lines 366 and 364 illustrates that composition 2 (line 366) produces a greater pressure at the outlet of pump 110 than composition 1 (line 364).
  • the comparison of lines 366 and 364 also illustrates that composition 2 (line 366) produces a greater pressure drop across column 125 as compared to composition 1 (line 364).
  • the average column pressure Pc 2 produced by composition 2 is greater than the average column pressure P B produced by composition 1.
  • FIG. 3B illustrates that increasing the mobile phase viscosity increases the average column pressure.
  • FIG. 3B also illustrates that decreasing the mobile phase viscosity decreases the average column pressure.
  • method 302 may further include comparing the new measured average column pressure to the identified average column pressure in step 332 after altering the composition in step 342.
  • the average column pressure Pc 2 produced by composition 2 in system 300 of FIG. 3B is closer to the identified average column pressure P A than the average column pressure P B produced by composition 1.
  • FIG. 3B illustrates that the mobile phase composition can be altered to more closely match a target average column pressure in a chromatography system.
  • the average column pressure Pc 2 produced by composition 2 in system 300 of FIG. 3B substantially matches the average column pressure P A of FIG. lA. Accordingly, by altering the composition as illustrated in FIG. 3B, even without adjusting the BPR set point, the average column pressure of a first chromatographic system can be substantially matched by the average column pressure in the second chromatographic system. Thus, the retention characteristics of analytes in the separation of FIG. 1A would be expected to substantially match those in the separation of FIG. 3B.
  • altering the mobile phase composition may have an effect on the separation. But that effect can be minimized by selecting a mobile phase component with very similar properties to the existing mobile phase. For example, a mobile phase consisting of 20% methanol and 80% carbon dioxide will have lower viscosity, but similar polarity to a mobile phase consisting of 20% methanol, 40% carbon dioxide, and 40% heptane.
  • FIG. 4 illustrates a chromatography system in accordance with embodiments of the invention in which the mobile phase composition is altered downstream of the outlet of the column.
  • FIG. 4 illustrates a chromatographic system 400 featuring a pump 110, a column 125, and a post-detector BPR 140.
  • a sample is introduced into the chromatographic systems of FIG. 4 upstream of the column 125.
  • Chromatographic system 400 of FIG. 4 features the same column 125 as system 150 of FIG. IB and system 300 of FIG. 3B.
  • the set point P x of the BPR 140 in system 400 of FIG. 4 is the same as that in FIGS. IB and 3B.
  • chromatographic system 400 of FIG. 4 includes makeup pump 455 between column 125 and detector 130. Makeup pump 455 pumps mobile phase comprising a different composition into system 400 at its location.
  • system 100 of FIG. 1 may be the first chromatographic system of step 322
  • system 400 of FIG. 4 may be the second
  • FIG. 4 illustrates the effect on the average column pressure in a chromatography system of altering the mobile phase composition by adding mobile phase fluid downstream of the column.
  • the addition of fluid changes the composition of the mobile phase downstream of the column 125 and increases the viscosity of the downstream mobile phase composition.
  • the mobile phase composition downstream of makeup pump 455 has a higher viscosity than the mobile phase composition upstream of makeup pump 455. It also increases the overall viscosity of the mobile phase in chromatographic system 400.
  • the pressure profile 460 of FIG. 4 illustrates, the increased viscosity of the altered composition produces a greater pressure drop across the post-column system tubing and therefore a higher average column pressure for the system.
  • the average column pressure Pc 3 produced by modifying the mobile phase composition with makeup pump 455 in system 400 of FIG. 4 is closer to the identified average column pressure P A than the average column pressure produced without modifying the mobile phase composition. Accordingly, FIG. 4 illustrates that the mobile phase composition can be altered to more closely match a target average column pressure in a chromatography system.
  • the average column pressure Pc 3 produced by modifying the mobile phase composition with makeup pump 455 in system 400 of FIG. 4 substantially matches the average column pressure P A of FIG. 1A. Accordingly, by altering the composition as illustrated in FIG. 4, even without adjusting the BPR set point, the average column pressure of a first chromatographic system can be substantially matched by the average column pressure in the second chromatographic system. Thus, the retention characteristics of analytes in the separation of FIG. 1A would be expected to substantially match those in the separation of FIG. 4.
  • the makeup fluid flow rate and composition can be programmed to compensate for continuously varying post-column pressure drops encountered across composition- programmed gradient separations.
  • the inventors further recognized that restrictive elements may be placed in the post-column tubing to increase the effect of the changing the
  • a restrictive element can be used to change the pressure characteristics of a chromatographic system.
  • a restrictive element can be added to adjust the average column pressure in a
  • restrictive elements include a short length of straight tubing featuring an inner diameter smaller than that of the upstream tubing, a tapered restrictor, a pinched restrictor, a fritted restrictor, an integral restrictor, and a crimped restrictor (e.g., a restriction formed by crimping a metal tube that reduces its inner diameter).
  • FIG. 5A illustrates a method 502 for efficiently transferring a carbon dioxide based separation procedure from a first chromatographic systems to a second
  • step 512 of FIG. 5A an average column pressure for a separation in a first chromatographic system is identified.
  • Step 512 is similar to step 212, and the variations described above with respect to FIG. 2A apply.
  • the average column pressure P A for the successful separation in first chromatographic system 100 of FIG. 1A is identified by mere reference to the know value.
  • step 522 of FIG. 5A involves a second
  • FIG. 5B illustrates a
  • FIG. 5B illustrates a chromatography system 500 including two columns 125 A, 125B. Columns 125 A and 125B of system 500 may together be substantially similar in many regards to column 125 in system 100. As FIG. 5 illustrates, a restrictive element 555 may be included between an outlet of the first column 125A and an inlet of the second column 125B in accordance with embodiments of the invention to couple the two columns. The inclusion of two columns affects the profile of the chromatographic system 500 of FIG. 5. In this illustrative example, chromatographic system 500 of FIG. 5B is the second chromatographic system of step 522.
  • a measured average column pressure for a separation in a second chromatographic system 500 is determined.
  • Step 522 is similar to step 222, and the variations described above with respect to FIG. 2A apply.
  • measurements may additionally be taken between any of the plurality of columns.
  • system 500 of FIG. 5B measurements may be taken between the outlet of pump 110 and the inlet of column 125 A, between the outlet of column 125A and the inlet of column 125B, and between the outlet of column 125B and the inlet of BPR 140.
  • measurements of system 500 are taken at the outlet of pump 110 and at the inlet of BPR 140.
  • measurements of system 500 are taken between the sample introduction and the inlet of column 125A and between the outlet of column 125B and the inlet of BPR 140. In some embodiments, measurements of system 500 are taken between the sample introduction and the inlet of column 125 A, between the outlet of column 125A and the inlet of column 125B, and between the outlet of column 125B and the inlet of BPR 140. In some embodiments, measurements of system 500 are taken between the sample introduction and the inlet of column 125 A, at the outlet of column 125 A, at the inlet of column 125B, and at the inlet of BPR 140. In some embodiments, measurements of system 500 are taken upstream of the inlet of column 125 A, and between the outlet of column 125B and the inlet of detector 130. In some embodiments,
  • measurements of system 500 are taken at the inlet and the outlet of column 125A and at the inlet and the outlet of column 125B. In some embodiments, measurements of system 500 are taken at the inlet of column 125 A and upstream of the outlet of column 125B. As discussed above with respect to step 222, step 522 involves averaging a plurality of measurements.
  • step 532 of FIG. 5A involves comparing the measured average column pressure for carbon dioxide based separation in the second chromatographic system with the identified average column pressure for carbon dioxide based separation in the first chromatographic system. Due to differences between column 120 and columns 125A and 125B, the average column pressure P A of the carbon dioxide based separation in the chromatographic system 100 of FIG. 1A is greater than the average column pressure of system 500 without restrictive element 555. In other words, the average column pressure for separation in system 500 without restrictive element 555 is less than the average column pressure P A for separation in system 100 of FIG. 1A. In a typical first comparison, the average column pressures do not substantially match and the difference would not be acceptable. For the purpose of this disclosure, we presume that the difference between the average column pressures is not acceptable. [0091] In step 542 of FIG. 5 A, a restrictive element is added to the second
  • the BPR set point represents the lower limit of the column pressure.
  • the inventors recognized that addition of a restrictive element will increase the pressure drop at the location of the restrictive element. For example, the inventors recognized that addition of a restrictive element will increase the pressure drop between the outlet of the column 125A and the inlet of the column 125B.
  • the inventors recognized that the pressure at the outlet of the column of the second system may not change significantly, or at all, as a result of adding a restrictive element upstream.
  • a restrictive element is added between the inlet of the first column downstream of the sample introduction and the inlet of the back pressure regulator downstream of the column in the second chromatographic system to more closely match the identified average column pressure for the carbon dioxide based separation in the first chromatographic system.
  • a restrictive element is added between the inlet of the first column downstream of the sample introduction and the inlet of the detector downstream of the column in the second chromatographic system.
  • a restrictive element may be added between any of the plurality of columns.
  • restrictive element 555 is added to system 500 to address the difference between the average column pressure P A of the carbon dioxide based separation in the chromatographic system 100 of FIG. 1A and the measured average column pressure in system 500 without restrictive element 555.
  • method 502 may further include determining a new measured average column pressure in step 522 after adding a restrictive element in step 542.
  • Pressure diagram 560 of FIG. 5B plots pressure with respect to system position.
  • Line 566 in pressure diagram 560 of FIG. 5B illustrates the pressure with respect to positions within chromatographic system 500 in accordance with embodiments of the invention. Any of the points along line 566 may represent column pressure measurements for system 500.
  • pressure diagram 560 illustrates that system 500 including restrictive element 555 as illustrated of FIG. 5B produces an average column pressure P R2 .
  • Pressure diagram 560 of FIG. 5B also illustrates a single BPR set point ⁇ .
  • the chromatographic systems of FIGS. 1A, IB, and 5B share BPR set point P x .
  • Line 566 illustrates that columns 125 A, 125B each produce a pressure drop.
  • Line 566 further illustrates that the inclusion of restrictive element 555 in system 500 produces a greater pressure drop between the inlet of first column and the outlet of the second column.
  • the pressure drop across the columns 125A, 125B allows the pressure upstream of the inlet of column 125A to be higher while still meeting the BPR set point ⁇ downstream of column 125B.
  • FIG. 5B illustrates that adding restrictive element 555 increases the average column pressure for system 500.
  • FIG. 5B suggests that a restrictive element can be selected to produce the desired pressure drop, and therefore the resulting average column pressure.
  • method 502 may further include comparing the new measured average column pressure to the identified average column pressure in step 532 after adding the restrictive element in step 342.
  • the average column pressure P R2 produced by system 500 with restrictive element 555 as illustrated in FIG. 5B is closer to the identified average column pressure P A than the average column pressure produced by system 500 without restrictive element 555.
  • FIG. 5B illustrates that a restrictive element may be added to a system to more closely match a target average column pressure in a chromatography system.
  • the average column pressure P R2 produced by system 500 with restrictive element 555 as illustrated in FIG. 5B substantially matches the average column pressure P A of FIG. 1A. Accordingly, by adding the restrictive element 555 as illustrated in FIG. 5B, even without adjusting the BPR set point, the average column pressure of a first chromatographic system can be substantially matched by the average column pressure in the second chromatographic system. Thus, the retention characteristics of analytes in the separation of FIG. 1A would be expected to substantially match those in the separation of FIG. 5B.
  • FIG. 6 illustrates a chromatographic system that may be used as the second system in another example of step 522 of method 502 of FIG. 5A.
  • FIG. 6 illustrates a chromatographic system 600 featuring pump 110, detector 130, and post-detector BPR 140 with set point P x .
  • FIG. 6 illustrates a chromatography system 600 including column 125, which includes particles with larger diameters than column 120 of system 100.
  • the inclusion of column 125 affects the profile of the chromatographic system 600 of FIG. 6.
  • a restrictive element 655 may be included between an outlet of column 125 and an inlet of detector 130 in accordance with embodiments of the invention.
  • step 522 of FIG. 5A a measured average column pressure for a separation in a second chromatographic system 600 is determined. Step 522 is similar to step 222, and the variations described above with respect to FIG. 2A apply.
  • step 532 of FIG. 5A involves comparing the measured average column pressure for carbon dioxide based separation in system 600 with the identified average column pressure for carbon dioxide based separation in system 100. Due to differences between column 120 and column 125, the average column pressure P A of the carbon dioxide based separation in the chromatographic system 100 of FIG. 1A is greater than the average column pressure of system 600 without restrictive element 655. In other words, the average column pressure for separation in system 600 without restrictive element 655 is less than the average column pressure P A for separation in system 100 of FIG. 1A. In a typical first comparison, the average column pressures do not substantially match and the difference would not be acceptable. For the purpose of this disclosure, we presume that the difference between the average column pressures is not acceptable.
  • restrictive element 655 is added to system 600 to more closely match the identified average column pressure P A for carbon dioxide based separation in the first chromatographic system.
  • restrictive element 655 is added between the outlet of column 125 and the inlet of detector 140 in system 600. The results of the separation in system 100 and system 600 may be compared to determine whether the procedure has been efficiently transferred to system 600.
  • method 502 may further include determining a new measured average column pressure in step 522 after adding restrictive element 655 in step 542.
  • Pressure diagram 660 of FIG. 6 plots pressure with respect to system position.
  • Line 666 in pressure diagram 660 of FIG. 6 illustrates the pressure with respect to positions within chromatographic system 600 in accordance with embodiments of the invention. Any of the points along line 666 may represent column pressure
  • pressure diagram 660 illustrates that system 600 including restrictive element 655 as illustrated of FIG. 6 produces an average column pressure P R3 .
  • Pressure diagram 660 of FIG. 6 also illustrates a single BPR set point ⁇ .
  • the chromatographic systems of FIGS. 1A, IB, and 6 share BPR set point ⁇ .
  • Line 666 further illustrates that the inclusion of restrictive element 655 in system 600 produces a pressure drop between the outlet of column 125 and the inlet of detector 140.
  • the pressure drop across restrictive element 655 allows the pressure upstream of detector 140 to be higher while still meeting the BPR set point ⁇ downstream.
  • FIG. 6 illustrates that adding restrictive element 655 increases the average column pressure for system 600.
  • FIG. 6 suggests that a restrictive element can be selected to produce the desired pressure drop, and therefore the resulting average column pressure.
  • method 502 may further include comparing the new measured average column pressure to the identified average column pressure in step 532 after adding the restrictive element in step 542.
  • the average column pressure P R3 produced by system 600 with restrictive element 655 as illustrated in FIG. 6 is closer to the identified average column pressure P A than the average column pressure produced by system 600 without restrictive element 655.
  • FIG. 6 illustrates that a restrictive element may be added to a system to more closely match a target average column pressure in a chromatography system.
  • the average column pressure P R3 produced by system 600 with restrictive element 655 as illustrated in FIG. 6 substantially matches the average column pressure P A of FIG. 1A. Accordingly, by adding the restrictive element 655 as illustrated in FIG. 6, even without adjusting the BPR set point ⁇ , the average column pressure of a first chromatographic system can be substantially matched by the average column pressure in the second chromatographic system. Thus, the retention characteristics of analytes in the separation of FIG. 1A would be expected to substantially match those in the separation of FIG. 6.

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Abstract

L'invention concerne des procédés permettant de transférer une procédure de séparation à base de dioxyde de carbone d'un premier système chromatographique à un second système chromatographique. Une pression de colonne moyenne pour la séparation dans le premier système est identifiée. Une pression de colonne moyenne mesurée pour la séparation dans le second système est déterminée. La pression de colonne moyenne mesurée est comparée à la pression de colonne moyenne identifiée. Pour correspondre plus étroitement à la pression moyenne de colonne identifiée, les procédés impliquent une ou plusieurs des étapes suivantes : (a) modification du débit de la phase mobile dans le second système ; (b) modification de la composition de la phase mobile dans le second système ; et/ou (c) ajout d'un élément restrictif entre les entrées d'une première colonne et le détecteur dans le second système.
PCT/US2017/044291 2016-07-29 2017-07-28 Procédé et appareil pour ajuster la pression moyenne de colonne dans un système de chromatographie pour approcher une pression moyenne de colonne identifiée WO2018022958A1 (fr)

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