Method for high pressure gradient chromatography using pump stroke control

1. A method of generating a flow having a composition gradient, the method comprising:

generating a plurality of pump strokes for a first pump in a system having at least the first pump and a second pump, each of the pump strokes for the first pump delivering a volume contribution of a first liquid-in response to a displacement volume of the first pump, the pump strokes of the first pump being generated at a pump stroke frequency; and

generating a plurality of pump strokes for the second pump, each of the pump strokes for the second pump delivering a volume contribution of a second liquid in response to a displacement volume of the second pump, the pump strokes for the second pump being generated at the pump stroke frequency and being interspersed in time with the pump strokes of the first pump, an initiation of each of the pump strokes of the second pump being offset in time relative to an initiation of a respective one of the pump strokes of the first pump such that variations in the flow rates of the first and second pumps based on the initiations of the pump strokes do not overlap in time, wherein the volume contributions of the pump strokes of each of the first and second pumps are controlled according to a predetermined composition gradient of a flow comprising the first and second liquids.

2. The method of claim 1 wherein each of the pump strokes of the second pump is initiated midway in time between an initiation of an immediately preceding pump stroke of the first pump and an initiation of an immediately following pump stroke of the first pump.

3. The method of claim 1 wherein, for each of the pump strokes of the second pump, an initiation of the pump stroke occurs after an initiation of the pump stroke of the first pump by a constant delay time.

4. The method of claim 1 wherein a phase difference between a sequence of consecutive pump strokes for the first pump and a sequence of consecutive pump strokes for the second pump is approximately 180°.

5. The method of claim 1 wherein the first and second liquids are solvents and wherein the flow is a mobile phase gradient comprising the solvents.

6. A pump system, comprising:

a first pump configured to deliver volume contributions of a first liquid, each of the volume contributions occurring during a pump stroke of the first pump and being responsive to a displacement volume of the first pump;

a second pump configured to deliver volume contributions of a second liquid, each of the volume contributions occurring during a pump stroke of the second pump and being responsive to a displacement volume of the second pump; and

a processor in communication with the first and second pumps, the processor configured to control the first and second pumps to have a same pump stroke frequency and to be interspersed in time so that initiations of the pump strokes of the first and second pumps are offset in time such that variations in the flow rates of the first and second pumps based on the initiations of the pump strokes do not overlap in time, the processor changing the volume contributions of the first and second pumps in time according to a predetermined composition gradient of a flow comprising the first and second liquids.

7. The pump system of claim 6 wherein the first and second pumps are solvent pumps and wherein the flow is a mobile phase gradient.

8. The pump system of claim 7 further comprising a mixer having an inlet in communication with the first pump to receive the solvent from the first pump, an inlet in communication with the second pump to receive the solvent from the second pump, and an outlet to provide the flow comprising the first and second solvent.

9. The pump system of claim 6 wherein each of the first and second pumps is configured with two pump heads in a serial arrangement and wherein one of the pump heads is a primary pump and the other of the pump heads is an accumulator pump.

10. The pump system of claim 6 wherein each of the first and second pumps is configured with two pump heads in a parallel arrangement and wherein the pump strokes of one of the pump heads is configured to operate in opposite phase from the pump strokes of the other pump head.

11. The pump system of claim 6 wherein the processor is configured to change the pump stroke frequency of the first and second pumps.

12. The pump system of claim 6 wherein the processor is configured to control the first and second pumps so that each initiation of the pump strokes of the second pump occurs approximately midway between each initiation of an immediately preceding pump stroke of the first pump and each initiation of an immediately following pump stroke of the first pump.

13. The pump system of claim 6 wherein the processor is configured to control the first and second pumps so that for each of the pump strokes of the second pump, an initiation of the pump stroke occurs after an initiation of the pump stroke of the first pump by a constant delay time.

14. The pump system of claim 6 wherein the processor is configured to control the first and second pumps so that a phase difference between a sequence of consecutive pump strokes for the first pump and a sequence of consecutive pump strokes for the second pump is approximately 180°.

15. A computer program product for generating a flow having a composition gradient, comprising:

a non-transitory computer readable storage medium having computer readable program code embodied therewith, when executed on a computer, the computer readable program code performing:

generating a plurality of pump strokes for a first pump in a system having at least the first pump and a second pump, each of the pump strokes for the first pump delivering a volume contribution of a first liquid in response to a displacement volume of the first pump, the pump strokes for the first pump being generated at a pump stroke frequency; and

generating a plurality of pump strokes for the second pump, each of the pump strokes for the second pump delivering a volume contribution of a second liquid in response to a displacement volume of the second pump, the pump strokes for the second pump being generated at the pump stroke frequency and being interspersed in time with the pump strokes of the first pump, an initiation of each of the pump strokes of the second pump being offset in time relative to an initiation of a respective one of the pump strokes of the first pump such that variations in the flow rates of the first and second pumps based on the initiations of the pump strokes do not overlap in time, wherein the volume contributions of the pump strokes of each of the first and second pumps are controlled according to a predetermined composition gradient of a flow comprising the first and second liquids.