Methods, devices, and systems for mixing fluids

Abstract

Improved methods, devices, and systems for mixing fluids, including small volumes of fluid, are provided. Pressing a pipette tip against an inner surface of a mixing vessel allows pressure to be applied within the tip. Greater pressure may be built-up than would be possible without engaging the tip with the mixing vessel. Disengaging the tip allows fluid flow through the tip, providing improved fluid mixing as compared to methods lacking engagement of a pipette tip with an inner surface of a mixing vessel while applying pressure within the pipette tip. Mixing vessels having features on an inner surface that are configured to engage a pipette tip, and to occlude an orifice of a pipette tip, are provided. Sample analysis devices and systems including pipette tips and mixing vessels configured to engage each other for pressure application within the tip are provided.

1 - 10 . (canceled) 
     
     
         11 . A method of mixing fluids using an automatic sample analysis device, comprising:
 Providing an automatic sample analysis device comprising a mixing vessel having an interior surface, and a pipette having a tip with an orifice;   Pressing said pipette tip into said mixing vessel effective that said pipette tip contacts said interior surface effective to occlude said orifice;   Applying pressure to fluid within said pipette tip;   Displacing said pipette tip effective to remove said occlusion of said orifice and to allow fluid flow through said orifice,   Whereby fluid is mixed within said mixing vessel.   
     
     
         12 . The method of  claim 11 , wherein said pressure comprises positive pressure effective to expel fluid from said pipette tip through said orifice and into said mixing vessel. 
     
     
         13 . The method of  claim 11 , wherein said pressure comprises negative pressure effective to draw fluid from said mixing vessel and into said pipette tip through said orifice. 
     
     
         14 . The method of  claim 11 , comprising alternating application of positive pressure and of negative pressure, wherein said alternating comprises a) applying positive pressure following application of negative pressure, wherein applying positive pressure is effective to expel fluid from said pipette tip through said orifice and into said mixing vessel, or b) applying negative pressure following said application of positive pressure, wherein applying negative pressure is effective to aspirate fluid from said mixing vessel and into said pipette tip through said orifice. 
     
     
         15 - 39 . (canceled) 
     
     
         40 . A method of mixing fluids by an automatic sample analysis device, comprising:
 Pressing a tip of a pipette against an interior surface of a mixing vessel, said pipette having a tip, an interior containing a fluid, and an orifice in said tip providing access to said pipette interior, said mixing vessel having an interior with an interior surface, effective that said pipette tip contacts said interior surface effective to occlude said orifice, wherein said pipette is operably connected to an automated pipette mechanism, said automated pipette mechanism comprising part of an automatic sample analysis device; then   Applying pressure to the fluid within said pipette tip; then   Displacing said pipette tip effective to remove said occlusion of said orifice and to allow fluid flow through said orifice,   Whereby fluid is mixed within said mixing vessel.   
     
     
         41 . The method of  claim 40 , wherein said pressure comprises positive pressure effective to expel fluid from said pipette tip through said orifice and into said mixing vessel. 
     
     
         42 . The method of  claim 40 , wherein said pressure comprises negative pressure effective to draw fluid from said mixing vessel and into said pipette tip through said orifice. 
     
     
         43 . The method of  claim 40 , comprising alternating application of positive pressure and of negative pressure, wherein said alternating comprises a) applying positive pressure following application of negative pressure, wherein applying positive pressure is effective to expel fluid from said pipette tip through said orifice and into said mixing vessel, or b) applying negative pressure following said application of positive pressure, wherein applying negative pressure is effective to aspirate fluid from said mixing vessel and into said pipette tip through said orifice. 
     
     
         44 . The method of  claim 40 , wherein the interior surface of the mixing vessel has a protrusion which extends into the interior of the mixing vessel, wherein said protrusion is configured to engage and occlude an orifice of a pipette tip when a pipette tip is placed onto or over the protusion. 
     
     
         45 . The method of  claim 40 , wherein the interior surface of the mixing vessel has a depression which extends away from the rest of the interior of the mixing vessel, wherein said depression is configured to engage and occlude an orifice of a pipette tip when a pipette tip is placed onto or into the depression. 
     
     
         46 . The method of  claim 44 , wherein said pressure comprises positive pressure effective to expel fluid from said pipette tip through said orifice and into said mixing vessel. 
     
     
         47 . The method of  claim 44 , wherein said pressure comprises negative pressure effective to draw fluid from said mixing vessel and into said pipette tip through said orifice. 
     
     
         48 . The method of  claim 45 , wherein said pressure comprises positive pressure effective to expel fluid from said pipette tip through said orifice and into said mixing vessel. 
     
     
         49 . The method of  claim 45 , wherein said pressure comprises negative pressure effective to draw fluid from said mixing vessel and into said pipette tip through said orifice.