DEVICES, SYSTEMS AND METHODS FOR FLOW-COMPENSATING PUMP-INJECTOR SYNCHRONIZATION

• US 20090062966A1
• Filed: 08/19/2005
• Published: 03/05/2009
• Est. Priority Date: 08/24/2004
• Status: Active Grant

• Current Assignee: Waters Technologies Corporation (Waters Corporation)
• Original Assignee: Waters Investments Limited (Waters Corporation)
• Inventors: Heden, John, Lamoureux, John, Ciavarini, Steven J., Soares, Miguel, Pensak, Stanley P. JR.
• Granted Patent: US 7,917,250 B2
• Time in Patent Office: Days
• US Class Current: 700/285
• CPC Class Codes: G01N 30/34 of fluid composition, e.g. gradient G01N30/36 takes precedence
• CPC Class Codes: G01N 35/1097 characterised by the valves valves in general F16K

Abstract

Systems, devices, and methods to mitigate the pressure disturbance associated with the injection of low-pressure analyte samples into a high-pressure HPLC fluid stream (52), to enhance chromatographic performance related to retention time and reproducibility. The preferred embodiment coordinates the injection run with active pressure control of a binary solvent delivery system (30) to virtually eliminate the customary pressure drop when the low-pressure loop is brought on line. An additional benefit that enhances reproducibility is accomplished by forcing a consistent timing relationship between the injection run, the mechanical position of the delivery pump pistons, and the start and subsequent gradient delivery.

Claims

1. A device for controlling introduction of an analyte sample at a first pressure into a fluid stream at a higher second pressure, wherein the fluid stream is that of a system for analyzing the analyte sample and introduction occurs during a forced transfer operation involving a plurality of pumping actuators having one dominant flow pumping actuator and at least one non-dominant flow pumping actuator, to minimize an expectant pressure drop that occurs when the analyte sample is introduced into said fluid stream, the device comprising:

a first signaling means for providing a first signal to the plurality of pumping actuators;

memory for storing a pre-determined injector pre-inject time delay and a pre-determined pump time delay;

a time-measuring means for measuring a first amount of time after the first signal and a second amount of time after the first signal;

a comparator for comparing the first and second amounts of time, respectively, to the pre-determined injector pre-inject time delay and the pre-determined pump time delay stored in memory;

a second signaling means for providing a second signal to the dominant pumping actuator of the plurality of pumping actuators when the second amount of time equals the pre-determined pump time delay; and

a third signaling means for providing a third signal to an injector valve through which the analyte sample is introduced into the fluid stream of the system when the first amount of time equals the pre-determined injector pre-inject time delay;

wherein the first signal causes the dominant flow pumping actuator and the non-dominant flow pumping actuator to perform a first forced transfer operation concurrently and the second signal causes only the dominant flow pumping actuator to perform a second forced transfer operation.

2. The device as recited in claim 1, wherein the device is a processor, microprocessor or a software algorithm that is executable on a processor or microprocessor.

3. The device as recited in claim 1, further comprising means to synchronize a mechanical phase of each pumping actuator with at least one of an injection sequence and a start of a gradient run to enhance retention time reproducibility between a plurality of injection runs.

4. The device as recited in claim 1, wherein the second forced transfer operation overlaps an injection event occurring when the analyte sample is introduced into the fluid stream of the system for analyzing the analyte sample.

5. The device as recited in claim 1, wherein the device is structured and arranged to provide active pressure control during each forced transfer operation to minimize disturbance in the fluid stream during introduction of the analyte sample.

6. A piece of software for controlling introduction of an analyte sample at a first pressure into a fluid stream at a higher second pressure, wherein the fluid stream is that of a system for analyzing the analyte sample, during a forced transfer operation involving a plurality of pumping actuators having one dominant flow pumping actuator and at least one non-dominant flow pumping actuator, to minimize an expectant pressure drop that occurs when the analyte sample is introduced into the fluid stream, the piece of software having an algorithm that comprises:

providing a first signal to a plurality of pumps;

storing a pre-determined injector pre-inject time delay and a pre-determined pump time delay in memory;

measuring a first amount time after the first signal and a second amount of time after the first signal;

comparing the first and second amounts of time, respectively, to the pre-determined injector pre-inject time delay and the pre-determined pump time delay stored in memory;

providing a second signal to the dominant flow pumping actuator of the plurality of pumping actuators when the second amount of time equals the pre-determined pump time delay; and

providing a third signal to an injector valve through which the analyte sample is introduced into the fluid stream of the system when the first amount of time equals the pre-determined injector pre-inject time delay.

7. The piece of software as recited in claim 6, wherein the algorithm ensures that the second forced transfer operation overlaps an injection event occurring when the analyte sample is introduced into the fluid stream of the system.

8. The piece of software as recited in claim 6, wherein the algorithm provides active pressure control during at least one forced transfer operation to minimize disturbance to the fluid stream during the injection event.

9. The piece of software as recited in claim 6, wherein the software algorithm further includes synchronizing a mechanical phase of each pumping actuator with at least one of an injection sequence and a start of a gradient run to enhance retention time reproducibility between a plurality of injection runs.

10. A system for controlling introduction of an analyte sample at a first pressure during active pressure control of a dominant flow pumping actuator, to minimize an expectant pressure drop that occurs when the analyte sample is introduced into a fluid stream at a second higher pressure of a system for analyzing said analyte sample, the control system comprising:

a control device for receiving pressure measurements and for providing signals for active pressure control;

a plurality of pumping actuators to provide high-pressure mixing of gradients of a plurality of solvents into a fluid stream of the system , wherein each of the plurality of pumping actuators is in fluid communication with a flow-combining device, and wherein

a dominant flow pumping actuator that is further in fluid communication with a first solvent source; and

one or more non-dominant flow pumping actuators that are further in fluid communication with a one or more solvent sources; and

an autosampler that is structured and arranged at an injector, to provide signals to the control device.

11. The system as recited in claim 10, wherein each of the dominant flow pumping actuator and one or more non-dominant flow pumping actuator includes:

a primary pumping actuator having a chamber and a piston that is disposed downstream of and in fluid communication with a solvent source; and

an accumulator pumping actuator having a chamber and a piston that is disposed downstream of and in series with the primary pumping actuator and upstream of an injector.

12. The system as recited in claim 11, wherein the system further includes a check valve that is disposed between the primary pumping actuator and the solvent source, wherein

in an open position, the check valve provides fluid communication between the primary pumping actuator and the solvent source so that the piston can intake solvent from the solvent source and store said solvent in the chamber, and

in a closed position, the check valve isolates the primary pumping actuator from the solvent source to prevent solvent in said chamber from flowing back into said solvent source when the piston of said primary pumping actuator compresses said solvent in said chamber or delivers said solvent to the chamber of the accumulator pumping actuator.

13. The system as recited in claim 11, wherein the system further includes a check valve that is disposed between the primary pumping actuator and the accumulator pumping actuator, wherein

in an open position, the check valve provides fluid communication between the chamber of the primary pumping actuator and the chamber of the accumulator pumping actuator so that the piston of the primary pumping actuator can deliver solvent to said chamber of said accumulator pumping actuator, and

in a closed position, the check valve isolates the chamber of the accumulator pumping actuator from the primary pumping actuator to prevent solvent in said chamber of said accumulator pumping actuator from flowing back into the chamber of said primary pumping actuator when the piston of said accumulator pumping actuator delivers said solvent to the system.

14. The system as recited in claim 11, wherein one or more of the chambers includes a pressure transducer that is disposed at an outlet thereof for providing pressure measurements to the device controller.

15. The system as recited in claim 10, wherein the flow-combining device is a T-section.

16. The system as recited in claim 10, wherein the flow-combining device is a mixer that can blend the two or more solvents prior to their introduction into the fluid stream.

17. The system as recited in claim 11, wherein the system is structured and arranged so that during a first forced transfer operation, the primary pistons of the dominant flow pumping actuator and the non-dominant flow pumping actuator compress their aspirated solvent;

re-fill their associated accumulator chambers; and

, further, deliver compressed solvent to the injector.

18. The system as recited in claim 11, wherein the system is structured and arranged so that during a second forced transfer operation, the primary piston of the dominant flow pumping actuator compresses its aspirated solvent;

re-fills its associated accumulator chamber; and

, further, delivers compressed solvent to the injector.

19. The system as recited in claim 11, wherein the system is structured and arranged so that active pressure control ensures that there is no overlap between a control period of the dominant flow pumping actuator and a control period of the non-dominant pump during a second forced transfer operation.

20. The system as recited in claim 19, wherein overlap between the control periods of the dominant flow pumping actuator and the non-dominant flow pumping actuator is avoided by advancing the control period of one of said pumping actuators having a longer pump cycle than the other of said pumping actuators.

21. The system as recited in claim 19, wherein during active pressure control, the dominant flow pumping actuator provides a greater share of solvent at the starting condition of a system run.

22. The system as recited in claim 21, wherein the dominant flow pumping actuator provides either an aqueous solvent or a solvent that is weaker that the solvent provided by the non-dominant flow pumping actuator.

23. The system as recited in claim 17, wherein the autosampler provides a first signal to the control device to initiate the first forced transfer operation.

24. The system as recited in claim 23, wherein the autosampler provides the first signal to the control device at some pre-determined, fixed time period prior to activating the injector to enable pump synchronization.

25. The system as recited in claim 24, wherein the pre-determined, fixed time period is sufficiently large to bring one of the dominant flow pumping actuator and the non-dominant flow pumping actuator into active pressure control coincident with introducing the analyte sample into the fluid stream.

26. The system as recited in claim 18, wherein the autosampler provides a second signal to the control device to initiate the second forced transfer operation.

27. The system as recited in claim 26, wherein the autosampler provides the second signal to the control device at some pre-determined, fixed time period prior to activating the injector to enable pump synchronization.

28. The system as recited in claim 27, wherein the pre-determined, fixed time period is sufficiently large to bring the dominant flow pumping actuator into active pressure control coincident with introducing the analyte sample into the fluid stream.

29. The system as recited in claim 18, wherein the system for analyzing said analyte sample is a high-performance liquid chromatography device.

30. A method of providing active pressure control to a system for controlling introduction of an analyte sample at a first pressure into a solvent fluid stream at a second higher pressure from one of a plurality of pumping actuators to minimize an expectant pressure drop that occurs when the analyte sample at a lower pressure is introduced into a system for analyzing said analyte sample, the method comprising:

preparing the analyte sample for introduction into the fluid stream;

initiating a first forced transfer operation, wherein the first forced transfer operation includes at least one of synchronizing a delivery stroke of a plurality of accumulator actuator pistons among the plurality of pumping actuators and synchronizing a mechanical phase of the plurality of accumulator actuator pistons;

initiating a second forced transfer operation, wherein the second forced transfer operation is applied only to the dominant flow pumping actuator while the non-dominant primary pumping actuator is in its rest state; and

activating an injector valve to introduce said analyte sample into the fluid stream of the system.

31. The method as recited in claim 30, wherein the first forced transfer operation is initiated at a first, pre-determined, fixed time delay prior to activating the injector valve.

32. The method as recited in claim 30, wherein the first forced transfer operation is initiated prior to the injection step to synchronize the dominant flow pumping actuator with the non-dominant flow pumping actuator.

33. The method as recited in claim 30, wherein the step of initiating a second forced transfer operation overlaps the step of activating the injector valve to introduce the analyte sample into the fluid stream of the system.

34. A device for controlling introduction of an analyte sample at a first pressure into a fluid stream at a higher second pressure, wherein the fluid stream is that of a system for analyzing the analyte sample, during a forced transfer operation involving a plurality of pumping actuators having one dominant flow pumping actuator and at least one non-dominant flow pumping actuator, to minimize an expectant pressure drop that occurs when the analyte sample is introduced into the fluid stream of the system, the device comprising:

memory for storing a pre-determined injector pre-inject time delay and a pre-determined pump time delay;

a time-measuring means for measuring a first amount of time after a first signal and a second amount of time after the first signal;

a comparator for comparing the first and second amounts of time, respectively, to the pre-determined injector pre-inject time delay and the pre-determined pump time delay stored in memory; and

a controller that;

provides the first signal to the plurality of pumps;

provides a second signal to the dominant pump of the plurality of pumps when the second amount of time equals the pre-determined pump time delay; and

provides a third signal to an injector valve through which the analyte sample is introduced into the fluid stream of the system when the first amount of time equals the pre-determined injector pre-inject time delay.

35. The device as recited in claim 34, wherein the first signal causes the dominant flow pumping actuator and the non-dominant flow pumping actuator to perform a first forced transfer operation concurrently and the second signal causes only the dominant flow pumping actuator to perform a second forced transfer operation.

36. The device as recited in claim 34, wherein the device further comprising means to synchronize a mechanical phase of each pumping actuator with at least one of an injection sequence and a start of a gradient run to enhance retention time reproducibility between a plurality of injection runs.

37. The device as recited in claim 34, wherein the second forced transfer operation overlaps an injection event occurring when the analyte sample is introduced into the fluid stream of the system.

38. The device as recited in claim 34, wherein the device is structured and arranged to provide active pressure control during each forced transfer operation to minimize disturbance in the fluid stream during introduction of the analyte sample into said fluid stream.