Dynamically adjusting set points for a heating/cooling element of a chromatography column using available information

12203,906

17/230325

April 14, 2021

The exemplary embodiments may determine a temperature set point for an outlet heater or cooler based on available information without requiring user input or requiring only minimal user input. The exemplary embodiments may estimate the temperature set point of the outlet heater based on available information, such as pressure delta along the column, temperature at the inlet of the chromatography column, and volumetric flow rate. In some instances, the estimate may be normalized for column dimensions, such as length and diameter. Tailing factor may also be used in determining the estimate. The estimate is not computationally burdensome and can be recalculated as the chromatography column is in use.

Waters Technologies Corporation (Milford, MA, US)

Waters Technologies Corporation (Milford, MA, US)

1. A chromatography system, comprising: a chromatography column having an inlet for receiving a mobile phase with an analyte and an outlet through which the mobile phase exits after flowing through the column; an outlet heater or cooler positioned to heat or cool at the outlet of the chromatography column; a controller for controlling an amount heating or cooling imparted by the heater or cooler, the controller configured for controlling the outlet heater or cooler to achieve a set point temperature for the outlet of the column, wherein the controller is configured to set the set point temperature for the outlet heater or cooler based on an estimate, wherein calculation of the estimate only requires values for a temperature at the inlet of the chromatography column, an offset value, an adjustment value, and a logarithmic function of a flow rate of the mobile phase and a pressure delta.

2. The chromatography system of claim 1 , further comprising an inlet heater or cooler positioned to impart heating or cooling to the mobile phase at or in proximity to the inlet of chromatography column.

3. The chromatography system of claim 1 , further comprising a vacuum insulating jacket for insulating at least a portion of the chromatography column.

4. The chromatography system of claim 1 , wherein the pressure delta is one of a pressure delta along the chromatography column or a pressure delta across the system.

5. The chromatography system of claim 1 , wherein the flow rate is a flow set for a pump in the chromatography system or is a flow rate through the column.

6. The chromatography system of claim 1 , further comprising an inlet sensor for sensing the temperature at or in proximity to the inlet of the chromatography column.

7. The chromatography system of claim 1 , wherein the flow rate and the pressure delta are used to estimate an amount of temperature increase or decrease realized by the mobile phase passing through the chromatography column.

8. The chromatography system of claim 1 , wherein the estimate is additionally based on at least one dimension of the chromatography column and/or peak asymmetry in chromatographic data for the chromatography column.

9. The chromatography system of claim 8 , wherein the at least one dimension of the liquid chromatography column comprises at least one of length of the chromatography column or diameter of the chromatography column.

10. The chromatography system of claim 1 , wherein the chromatography system further comprises an inlet heater or cooler positioned to heat or cool the mobile phase at the inlet of the chromatography column having a set point temperature and wherein the controller assumes that the temperature at the inlet of the chromatography column is the set point temperature for the inlet heater.

11. The chromatography system of claim 1 , wherein the chromatography system further includes a temperature sensor in proximity to the inlet and wherein the controller assumes that the temperature at the inlet of the chromatography column is the temperature sensed by the temperature sensor.

12. The chromatography system of claim 1 , wherein the chromatography column is a liquid chromatography column.

13. The chromatography system of claim 1 , wherein the chromatography column is supercritical fluid chromatography column.

14. The chromatography system of claim 1 , further comprising a control loop for maintaining the temperature at the outlet at the set point.

15. The chromatography system of claim 1 , wherein the controller estimates the set point temperature for the outlet heater or cooler (T out) as: T out =T in +(ln(ΔP×F v)+offset)/adjustment factor, where T in is the temperature of the mobile phase at the inlet of the chromatography column, ln is a natural logarithm, ΔP is the pressure delta of the chromatography column, Fv is the flow rate of the mobile phase through the chromatography column, offset is an offset value, and adjustment factor is a value.

16. A controller for controlling an outlet heater or cooler of a chromatography column, comprising: a processing logic for: receiving a temperature at an inlet to the chromatography column, receiving a magnitude of pressure delta, receiving a flow rate of mobile phase; determining a temperature set point of the outlet heater or cooler wherein the determining of the temperature set point requires only values for the temperature at the inlet to the chromatography column, an offset value, an adjustment factor, and a logarithmic function of the magnitude of the pressure delta and the flow rate of the mobile phase; and a signal generator for generating a control signal for controlling the temperature set point of the outlet heater or cooler.

17. The controller of claim 16 , wherein the received temperature at the inlet is one of a temperature of the mobile phase at or near the inlet, a temperature of the inlet, a temperature set point of a mobile phase heater or an inlet heater or a temperature of the inlet.

18. A method of setting a desired temperature set point for an outlet heater or cooler for imparting heating or cooling to an outlet of a chromatography column in a chromatography system, comprising: determining with processing logic an estimate of the desired set point for the outlet heater or cooler, wherein the determining requires only values for a volumetric flow rate, a change in pressure, an offset value, an adjustment factor, and a temperature at an inlet of the chromatography column; and setting the desired set point for the outlet heater or cooler via a control signal to be the determined estimate.

19. The method of claim 18 , wherein the change in pressure is across the column or across the system.

20. The method of claim 18 , wherein the determining the estimate comprises determining the estimate of the desired set point (Tout) as: T out= T in+(ln(Δ P×Fv)+offset)/adjustment factor, where Tin is the temperature of the mobile phase at the inlet of the chromatography column, ln is a natural logarithm, ΔP is the pressure delta of the chromatography column, Fv is the flow rate of the mobile phase through the chromatography column, offset is an offset value, and adjustment factor is a value.

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International Search Report and Written Opinion for International application No. PCT/US2021/027243, mailed on Jul. 20, 2021, 11 pages. cited by applicant
International Preliminary Report on Patentability for International Patent Application No. PCT/US2021/027243, mailed Oct. 7, 2022. cited by applicant

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