Solvent delivery system for liquid chromatography that maintains fluid integrity and pre-forms gradients

Patent metadata

Field	Value
Publication number	US-9103814-B2
Application number	US-28058507-A
Country	US
Kind code	B2
Filing date	Mar 16, 2007
Priority date	Mar 17, 2006
Publication date	Aug 11, 2015
Grant date	Aug 11, 2015

Abstract

A solvent delivery subsystem for a chromatography device performs relatively low pressure, high flow mixing of solvents to form a gradient and subsequent high pressure, low flow delivery of the gradient to the separation column. The mixing of the gradient is independent and does not interfere with the gradient delivery. To form the gradient, the outputs of an aqueous pump and an organic pump are mixed to fill a storage capillary while a downstream point from the storage capillary is vented to atmosphere. After gradient formation, the vent to atmosphere is closed, the solvent delivery system rises to high pressure, and only the aqueous pump runs for gradient delivery. To maintain integrity of the fluid stream, the solvent delivery system uses feed forward compensation and controls at least one parameter selected from the group consisting of pressure and flow in the conduit means to follow a gradual ramp.

First claim

What is claimed is:

1. A system for providing a gradient to a nano-flow capillary liquid chromatography device, the system comprising:
an aqueous pump for producing a first output and for delivering the gradient;
an organic pump for producing a second output mixed with the first output to produce a solution;
a processing device for controlling the pumps;
a storage capillary for forming the gradient from a portion of the solution;
a fitting connected to the storage capillary, wherein the fitting forms a first outlet connected to the nano-flow capillary liquid chromatography device and a second outlet; and
a valve connected to the second outlet and controlled by the processing device designed to form the gradient in the storage capillary by opening the valve to direct resident fluid to waste while the aqueous and organic pumps run to form the gradient, wherein to deliver the gradient to the nano-flow capillary liquid chromatography device, and closing the valve so that the aqueous pump runs to deliver the gradient and the organic pump is offline.

2. A system as recited in claim 1 , further comprising:
a first inline pressure transducer and a first flow transducer for receiving the first output; and
a second inline pressure transducer and a second flow transducer for receiving the second output; wherein each transducer is in communication with the processing device to provide closed-loop feedback control.

3. A system as recited in claim 1 , wherein the storage capillary is sized to minimize backpressure and dispersion to preserve integrity of the formed gradient.

4. A system as recited in claim 1 , further comprising fluid combining fitting for mixing the first and second outputs into one fluid stream.

5. A system as recited in claim 1 , wherein the nano-flow capillary liquid chromatography device includes a separations column, an injector for receiving the gradient and directing the gradient to the separations column, and a thermally managed compartment for housing the separations column and the injector, and wherein the storage capillary, the fitting and the valve are co-located in the thermally managed compartment.

6. A system as recited in claim 1 , further comprising a transport line that connects the fitting to a sample injector of the nano-flow capillary liquid chromatography device.

7. A system as recited in claim 6 , wherein the transport line is a capillary tube.

8. A system as recited in claim 6 , wherein the gradient is formed and delivered to flow along a path without changing direction.

9. A system as recited in claim 6 , wherein the fitting is a T-shaped fitting arranged so that during delivery, the gradient flows from the inlet to the first outlet without changing direction.

10. A system for providing a gradient to a nano-flow capillary liquid chromatography device, the system comprising:
an aqueous pump for producing a first output and for delivering the gradient;
an organic pump for producing a second output mixed with the first output to produce a solution;
a processing device for controlling the pumps;
a storage capillary for receiving a gradient formed from both the aqueous and organic pump at low pressure;
a fitting connected to the storage capillary, wherein the fitting forms a first outlet connected to the nano-flow capillary liquid chromatography device and a second outlet; and
a valve connected to the second outlet and controlled by the processing device designed to form the gradient in the storage capillary by opening the valve to direct resident fluid to waste while the aqueous and organic pumps run to form the gradient, wherein to deliver the gradient to the nano-flow capillary liquid chromatography device, and closing the valve so that the aqueous pump runs to deliver the gradient at high pressure and the organic pump is not active.

11. A system as recited in claim 10 , further comprising:
a first inline pressure transducer and a first flow transducer for receiving the first output; and
a second inline pressure transducer and a second flow transducer for receiving the second output; wherein each transducer is in communication with the processing device to provide closed-loop feedback control,
wherein the storage capillary is sized to minimize backpressure and dispersion to preserve integrity of the gradient.

12. A system as recited in claim 10 , further comprising fluid combining fitting for mixing the first and second outputs into one fluid stream.

13. A system as recited in claim 10 , wherein the nano-flow capillary liquid chromatography device includes a separations column, an injector for receiving the gradient and directing the gradient to the separations column, and a thermally managed compartment for housing the separations column and the injector, and wherein the storage capillary, the fitting and the valve are co-located in the thermally managed compartment.

14. A system as recited in claim 10 , further comprising a transport line that connects the fitting to a sample injector of the nano-flow capillary liquid chromatography device.

15. A system as recited in claim 10 , wherein the gradient is formed and delivered to flow along a path in a single direction.

16. A system as recited in claim 10 , wherein the fitting is a T-shaped fitting arranged so that during delivery, the gradient flows from the inlet to the first outlet in a straight direction.

Assignees

• Ciavarini Steven J
• Pensak Jr Stanley P
• Finch Jeffrey W
• Fadgen Keith
• Liu Hongji
• Waters Technologies Corp

Inventors

• Ciavarini Steven J
• Pensak Jr Stanley P
• Finch Jeffrey W
• Fadgen Keith
• Liu Hongji

Classifications

• G01N30/34 Primary

  of fluid composition, e.g. gradient (G01N30/36 takes precedence) · CPC title

• G01N2030/326

  pumps · CPC title

• G05D11/132

  by controlling the flow of the individual components (G05D11/133 takes precedence) · CPC title

• G01N30/32

  of pressure or speed (G01N30/36 takes precedence) · CPC title