State-variable control system

Abstract

The invention relates to a state-variable feedback control system for monitoring and optimally controlling the operation of a microfluidic aspirate dispense-system. A steady state operating pressure is determined from the fluid, flow and/or operational characteristics of the system. Measurements from one or more pressure sensors are part of the control strategy to derive information for active feedback control and/or to achieve the desired operating pressure. Advantageously, the control system adds to the versatility of the aspirate-dispense system, for example, by permitting rapid dispensing of drops of different size. The control system also desirably facilitates efficient, repeatable and accurate performance and reduces wastage of valuable reagents or fluid.

What is claimed is:  
     
         1 . A method of active feedback control to monitor and control the operation of a liquid reagent delivery system for transferring predetermined quantities of reagent from a reagent source to predetermined locations on or in a target, comprising: 
 providing a finite state machine controller for controlling the operation of a positive displacement pump and a solenoid-actuated dispenser hydraulically arranged in series with said positive displacement pump and for controlling relative motion between said reagent source, said target and said dispenser;    determining a steady state dispense pressure based on the fluid dynamical characteristic equations of said delivery system;    operating said positive displacement pump to substantially overcome elastic compliance within said delivery system and build pressure within said delivery system to said steady state dispense pressure;    operating said positive displacement pump and opening and closing said dispenser at a predetermined frequency to dispense said reagent in the form of one or more droplets;    providing relative motion between said dispenser and said target to dispense said droplets at said predetermined locations on or in said target;    monitoring said pressure within said delivery system using a pressure sensor and comparing it to said steady state dispense pressure; and    actively adjusting said pressure in response to any substantial deviation of said pressure from said steady state dispense pressure to generally maintain said steady state pressure within said delivery system.    
     
     
         2 . The method of  claim 1 , wherein said method further comprises aspirating said reagent from said reagent source into said dispenser.  
     
     
         3 . The method of  claim 1 , wherein said method further comprises estimating and monitoring the Reynolds number.  
     
     
         4 . The method of  claim 1 , wherein said method further comprises estimating and monitoring the Weber number.  
     
     
         5 . The method of  claim 1 , wherein said method further comprises estimating and monitoring the elastic compliance.  
     
     
         6 . The method of  claim 1 , wherein said method further comprises estimating the density (ρ) of said reagent.  
     
     
         7 . The method of  claim 1 , wherein said method further comprises estimating the viscosity (μ) of said reagent.  
     
     
         8 . The method of  claim 1 , wherein said method further comprises adjusting said steady state dispense pressure to dispense droplets of varying size.  
     
     
         9 . The method of  claim 1 , wherein said method further comprises adjusting said steady state dispense pressure to dispense droplets of varying exit velocity.  
     
     
         10 . The method of  claim 9 , wherein said method further comprises estimating and monitoring the exit velocity.  
     
     
         11 . A method of providing active feedback control during the operation of a fluid handling system for transferring fluid from one or more sources to one or more targets, said fluid handling system comprising a dispenser hydraulically coupled to a direct current fluid source, an apparatus for providing relative motion between said dispenser and said one or more sources and said one or more targets, and a finite state machine controller for controlling the operation of said fluid handling system, said method comprising: 
 computing or estimating a generally steady state dispense pressure from the fluid and/or flow diagnostics of said system;    stabilizing system pressure within said system to set it at said steady state dispense pressure by actuating said direct current fluid source and/or said dispenser;    operating said direct current fluid source, said dispenser and said apparatus to deposit predetermined quantities of said fluid at predetermined locations;    monitoring said system pressure using one or more pressure sensors; and    adjusting said system pressure and/or operational parameters in response to any substantial deviations of said system pressure from said steady state dispense pressure to provide accurate dispensing.    
     
     
         12 . The method of  claim 11 , wherein depositing said quantities of said fluid comprises dispensing said quantities in the form of one or more droplets.  
     
     
         13 . The method of  claim 12 , wherein said method further comprises selecting a dispense volume for each of said droplets.  
     
     
         14 . The method of  claim 11 , wherein computing or estimating a generally steady state dispense pressure comprises estimating the fluid density (ρ).  
     
     
         15 . The method of  claim 14 , wherein computing or estimating a generally steady state dispense pressure comprises estimating the fluid viscosity (μ).  
     
     
         16 . The method of  claim 15 , wherein the density and viscosity are estimated using transient pressure measurements.  
     
     
         17 . The method of  claim 11 , wherein computing or estimating a generally steady state dispense pressure comprises: 
 estimating the capillary flow resistance (Rc) and orifice flow resistance (Ro) of a nozzle through which said fluid is dispensed; and    calculating the fluid pressure drop through the nozzle during generally steady state dispensing to estimate the steady state dispense pressure (Pss) using the relationship:      Pss=QRc +( QRo ) 2      where, Q is the flow rate.    
     
     
         18 . The method of  claim 11 , wherein computing or estimating a generally steady state dispense pressure comprises: 
 estimating the resistance to fluid flow through the system by perturbing or modulating the flow rate about the desired flow rate to estimate the capillary flow resistance (Rc) and orifice flow resistance (Ro); and    calculating the fluid pressure drop during dispensing to estimate the steady state dispense pressure (Pss) using the relationship:      Pss=QRc +( QRo ) 2      where, Q is the flow rate.    
     
     
         19 . The method of  claim 11 , wherein said method further comprises adjusting said steady state dispense pressure to dispense fluid droplets of varying size and/or exit velocity.  
     
     
         20 . The method of  claim 11 , wherein said method further comprises aspirating said fluid from said one or more sources.  
     
     
         21 . The method of  claim 11 , wherein said method further comprises estimating and monitoring the Reynolds number.  
     
     
         22 . The method of  claim 11 , wherein said method further comprises estimating and monitoring the Weber number.  
     
     
         23 . The method of  claim 11 , wherein said method further comprises estimating and monitoring compliance within said system.