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

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.

1 - 68 . (canceled) 
     
     
         69 . A solvent delivery system for a liquid chromatography system, comprising:
 a first leg including a first pump for introducing a first solvent into the first leg;   a second leg including a second pump for introducing a second solvent into the second leg;   a mixing tee positioned at a junction between the first leg and the second leg for mixing the first solvent form the first leg with the second solvent from the second leg;   a controller comprising a processor for providing open loop feed forward control of the first pump and the second pump based on a parameter of stored energy in the liquid chromatography system.   
     
     
         70 . The solvent delivery system of  claim 69 , further comprising a first pressure sensor for measuring pressure in the first leg and a second pressure sensor for measuring pressure in the second leg, wherein the first pressure sensor and the second pressure sensor are configured to provide pressure measurements to the controller. 
     
     
         71 . The solvent delivery system of  claim 69 , wherein the parameter is a ratio of compressibility for the first solvent and the second solvent. 
     
     
         72 . The solvent delivery system of  claim 71 , wherein the controller is configured for controlling the first pump and the second pump based on the ratio of compressibility. 
     
     
         73 . The solvent delivery system of  claim 69 , further comprising a first flow sensor for measuring flow rate in the first leg and a second flow sensor for measuring flow rate in the second leg, wherein the first flow sensor and the second flow sensor are configured to provide flow rate measurements to the controller. 
     
     
         74 . The solvent delivery system of  claim 73 , wherein the controller is configured for determining a fluid capacitance of the first leg and a fluid capacitance of the second leg, wherein the fluid capacitance of the first leg is a product of a fluid compressibility constant for the first solvent and a captive fluidic volume in the first leg from the first pump to the first flow sensor and wherein the fluid capacitance of the second leg is a product of a fluid compressibility constant for the second solvent and a captive fluidic volume in the second leg from the second pump to the second flow sensor. 
     
     
         75 . The solvent delivery system of  claim 74 , wherein the controller is configured for generating a feedforward correction for the first pump as a product of a disturbance value for the first leg and the fluid capacitance of the first leg and the controller is configured for generating a feedforward correction for the second pump as a product of a disturbance value for the second leg and the fluid capacitance of the second leg. 
     
     
         76 . The solvent delivery system of  claim 75 , the disturbance value for the first leg is an estimate and the disturbance value for the second leg is an estimate. 
     
     
         77 . The liquid chromatography system of  claim 75 , wherein the disturbance value for the first leg is a measured value and the disturbance value for the second leg is a measured value. 
     
     
         78 . The solvent delivery system of  claim 75 , wherein the controller is configured to generate a control signal for the first pump that encodes a sum of the feedforward correction for the first pump and a feedback correction for the first pump, where the feedback correction for the first pump is a difference between a desired flow and a measured flow as measured by the first flow sensor. 
     
     
         79 . The solvent delivery system of  claim 75 , wherein the first pump has a plunger and the second pump has a plunger, wherein the controller is configured to correct the fluid capacitance for the first leg based on position of the plunger of the first pump before generating the feedforward correction for the first pump, and wherein the controller is configured to correct the fluid capacitance for the second leg based on position of the plunger of the second pump before generating the feedforward correction for the second pump. 
     
     
         80 . The solvent delivery system of  claim 69 , further comprising conduits or series restrictors in the first leg and/or the second leg to provide passive fluidic decoupling between the first pump and the second pump. 
     
     
         81 . A method, comprising:
 pumping a first solvent with a first pump in a first leg of a solvent delivery system;   pumping a second solvent with a second pump in a second leg of the solvent delivery system;   mixing the first solvent and the second solvent at a mixing tee positioned at a junction of the first leg and the second leg;   controlling the first pump and the second pump with a controller that provides open loop feed forward control of the first pump and the second pump based on a parameter of stored energy in the liquid chromatography system.   
     
     
         82 . The method of  claim 81 , wherein the parameter is a ratio of compressibility for the first solvent and the second solvent. 
     
     
         83 . The method of  claim 81 , further comprising:
 using a first flow sensor to measure flow rate in the first leg;   using a second flow sensor to measure flow rate in the second leg; and   providing flow rate measurements from the first flow sensor and the second flow sensor to the controller.   
     
     
         84 . The method of  claim 83 , wherein the controlling the first pump and the second pump with the controller comprises the controller determining a fluid capacitance of the first leg and a fluid capacitance of the second leg, wherein the fluid capacitance of the first leg is a product of a fluid compressibility constant for the first solvent and a captive fluidic volume in the first leg from the first pump to the first flow sensor and also comprises the controller determining the fluid capacitance of the second leg is a product of a fluid compressibility constant for the second solvent and a captive fluidic volume in the second leg from the second pump to the second flow sensor. 
     
     
         85 . The method of  claim 84 , wherein the controlling the first pump and the second pump with the controller comprises generating a feedforward correction for the first pump as a product of a disturbance value for the first leg and the fluid capacitance of the first leg and is configured for generating a feedforward correction for the second pump as a product of a disturbance value for the second leg and the fluid capacitance of the second leg. 
     
     
         86 . The method of  claim 85 , wherein the controlling the first pump and the second pump with the controller comprises generating a control signal with the controller for the first pump that encodes a sum of the feedforward correction for the first pump and a feedback correction for the first pump, where the feedback correction for the first pump is a difference between a desired flow and a measured flow as measured by the first flow sensor. 
     
     
         87 . The method of  claim 85 , wherein the first pump has a plunger and the second pump has a plunger and wherein the controlling the first pump and the second pump with the controller comprises correcting the fluid capacitance for the first leg with the controller based on position of the plunger of the first pump before generating the feedforward correction for the first pump, and correcting the fluid capacitance for the second leg with the controller based on position of the plunger of the second pump before generating the feedforward correction for the second pump. 
     
     
         88 . The method of  claim 81 , further comprising placing conduits or series restrictors in the first leg and/or the second leg to provide passive fluidic decoupling between the first pump and the second pump.