Dispensing method and apparatus for dispensing very small quantities of fluid

Abstract

A fluid dispensing system and method includes a pump to aspirate and expel sample fluid, a fluid dispensing tip, and a metering station. The fluid dispensing tip includes a working fluid and an air gap where the air gap separates the working fluid from the sample fluid. The metering station receives a drop of sample fluid that is at least twice as large as the pre-determined volume to ultimately be dispensed. The fluid dispensing tip then withdraws the predetermined volume of fluid from the sample fluid. Precise volumes are ascertained by prior knowledge of the geometry of the fluid dispensing tip and by using an imaging device to monitor an interface of either the sample fluid or working fluid with the air gap within the fluid dispensing tip. The system and method are capable of accurately dispensing very small volumes of sample fluid on the order of 10 picoliters. In addition, the system and method do not require large volumes of sample fluid to prime a pump mechanism.

I claim:  
     
         1 . An apparatus for dispensing specified volumes of fluid, the apparatus comprising: 
 a fluid dispensing tip, said fluid dispensing tip being configured to contain 1 picoliter to 10 nanoliters of a sample fluid at an end, an air gap positioned above the sample fluid, and a working fluid positioned above said air gap;    a pump adapted to maintain said working fluid in said fluid-dispensing tip and adapted to aspirate a first volume of said sample fluid into said fluid dispensing tip and expel said first volume of said sample fluid from said fluid dispensing tip,    a metering station having an inert surface positioned to receive a drop of said sample fluid from said fluid-dispensing tip; and    means for selectively retrieving a second volume of said sample fluid from said drop on said metering station which is smaller than said first volume and dispensing said second volume of said sample fluid at a desired location.    
     
     
         2 . The apparatus of  claim 1  wherein said means for selectively retrieving includes an imaging device focused on at least one of an interface between said sample fluid and said air gap and said interface between said air gap and said working fluid.  
     
     
         3 . The apparatus of  claim 1  wherein said second volume ranges from 1 picoliter to 10 nanoliters.  
     
     
         4 . The apparatus of  claim 1  wherein said second volume is on the order of 10 picoliters.  
     
     
         5 . The apparatus of  claim 1  wherein said fluid dispensing tip is transparent  
     
     
         6 . The apparatus of  claim 1  wherein said metering station has a drop receiving surface constructed from polytetrafluoroethylene.  
     
     
         7 . The apparatus of  claim 1  wherein said fluid dispensing tip has a relatively larger volume area for containing said working fluid compared to said end which receives said first volume of said sample fluid.  
     
     
         8 . An apparatus for dispensing specified volumes of fluid, comprising: 
 a transparent fluid dispensing tip adapted to contain a working fluid,    a pump adapted to maintain said working fluid in said transparent fluid dispensing tip and adapted to aspirate a volume of fluid into said transparent fluid dispensing tip such that a bottom surface of said working fluid, a top surface of an aspirated fluid, and an air gap between said bottom surface of said working fluid and said top surface of an aspirated fluid are positioned in said transparent fluid dispensing tip, and    an imaging device for providing an image of at least one of an interface between said air gap and said working fluid and said air gap and said aspirated fluid.    
     
     
         9 . A method for dispensing specified volumes of fluid, comprising the steps of: 
 aspirating a sample fluid into a fluid dispensing tip which contains a working fluid, said aspirating step being performed such that said working fluid and said sample fluid are separated by an air gap,    dispensing a first volume of said sample fluid onto a metering station surface to form a drop on said metering station surface;    aspirating a portion of said drop from said metering station surface into said fluid dispensing tip, said portion constituting a second volume of said sample fluid which is smaller than said first volume; and    dispensing said portion from said fluid dispensing tip.    
     
     
         10 . The method of  claim 9  wherein said first volume of said sample fluid dispensed in said first dispensing step is at least twice as large as the second volume of said sample fluid aspirated in said second aspirating step.  
     
     
         11 . The method of  claim 9  further comprising the step of applying vibrations to said fluid dispensing step during at least one of said two aspirating steps and said two dispensing steps.  
     
     
         12 . The method of  claim 9  wherein said second aspirating step includes iteratively applying suction and expelling fluid from said fluid dispensing tip until a desired second volume of sample fluid is positioned within said fluid dispensing tip.  
     
     
         13 . The method of  claim 9  wherein said second volume of sample fluid ranges from 1 picoliter to 10 nanoliters.  
     
     
         14 . The method of  claim 13  wherein said second volume of sample fluid is on the order of 10 picoliters.  
     
     
         15 . The method of  claim 9  further comprising the step of imaging an interface between said air gap and said working fluid.  
     
     
         16 . The method of  claim 9  further comprising the step of imaging an interface between said air gap and said sample fluid.  
     
     
         17 . A method for dispensing a predetermined volume of a fluid, comprising the steps of 
 aspirating a fluid into a transparent fluid dispensing tip, said fluid dispensing tip housing a working fluid and an air gap, said air gap being positioned between said working fluid and said fluid aspirated in said aspirating step,    adjusting a fluid in said fluid dispensing tip to a predetermined volume by visually monitoring a position of said air gap; and    dispensing said predetermined volume of said fluid aspirated in said aspirating step.