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
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.
대표청구항▼
1. An automatic sample analysis device comprising a pipette, a programmable processor in communication with said pipette, a mixing vessel having an interior cavity having an interior surface, and a pipette tip having a lip defining an orifice, wherein said automatic sample analysis device has the pr
1. An automatic sample analysis device comprising a pipette, a programmable processor in communication with said pipette, a mixing vessel having an interior cavity having an interior surface, and a pipette tip having a lip defining an orifice, wherein said automatic sample analysis device has the programmable processor configured to mix fluids within the mixing vessel following occlusion of said orifice of the pipette tip against an inner surface of the mixing vessel, by instructing the pipette to apply pressure to fluid in the pipette tip during said occlusion, and then removing said pipette tip from contact with said inner surface of the mixing vessel, effective to remove said occlusion of said orifice effective that fluid flows through said orifice, whereby fluid is mixed within the mixing vessel. 2. The automatic sample analysis device of claim 1, wherein said mixing vessel comprises a feature configured to engage said pipette tip, effective that when the lip of said pipette tip is pressed against said interior surface, said orifice is occluded effective to prevent fluid flow through the orifice. 3. The automatic sample analysis device of claim 2, wherein said feature configured to engage the lip of said pipette tip of said fluid handling apparatus comprises a tapered indentation in said interior surface of said vessel. 4. The automatic sample analysis device of claim 3, wherein said tapered indentation in said interior surface of said vessel further comprises a convex feature extending towards the interior cavity of said mixing vessel, wherein said convex feature is configured to extend at least partially into said orifice effective to occlude the orifice. 5. The automatic sample analysis device of claim 2, wherein said feature configured to engage the lip of said pipette tip comprises a convex feature extending into said interior cavity of said mixing vessel and configured to extend at least partially into said orifice effective to occlude the orifice when the pipette tip is pressed against said interior surface, said orifice is occluded effective to prevent fluid flow through the orifice. 6. The automatic sample analysis device of claim 2, wherein said feature configured to engage the tip of said fluid handling apparatus comprises a conical or tapered feature extending from into the interior of the mixing vessel. 7. A system for mixing small volumes of fluid comprising: i) a fluid handling apparatus comprising a controller, a base in communication with the controller; at least one head operably connected with said base; at least one nozzle operably connected with said at least one head and having a pathway for fluid flow between said nozzle and said head; wherein said at least one head comprises mechanical and structural components operable with each nozzle, and wherein said at least one nozzle is configured to engage a pipette tip, effective that a pipette tip may be held by a nozzle; a pipette tip having an interior passage therethrough and comprising a proximal end configured to engage with a nozzle effective that said pipette tip may be held by the nozzle, and a distal end having a lip defining an orifice, wherein said orifice is continuous with and connected to said interior passage, wherein when a pipette tip is held by a nozzle, i) a continuous pathway for fluid flow is provided between the orifice of said pipette tip, the pipette tip interior passage, the nozzle holding the pipette tip, and the head associated with the nozzle; and ii) the pipette tip may be sealed to the nozzle effective that positive-pressure or suction within the pipette tip is effective to cause fluid flow into or out of the orifice of the pipette tip without dislodging the pipette tip from the nozzle; and a source of positive-pressure or suction in fluid contact with one or more of the pipette tip, the nozzle, the head, and the base, effective that said source may apply positive-pressure or suction within the pipette tip effective to cause fluid flow into or out of the orifice of the pipette tip, andii) a mixing vessel comprising an interior portion defined by an interior surface having an interior wall and a bottom, said interior portion having an engagement region, wherein said engagement region comprises a concave or convex feature configured to engage said lip of the pipette tip, effective that when the lip of the pipette tip is pressed against said concave or convex feature, the orifice is occluded effective to prevent fluid flow through the orifice;wherein the controller is configured to mix fluid within the mixing vessel following occlusion of the orifice of the pipette tip against the inner surface of the mixing vessel, by instructing the head to apply pressure to fluid in the pipette tip during said occlusion, and then removing said pipette tip from contact with said inner surface of the mixing vessel, effective to remove said occlusion of said orifice effective that fluid flows through said orifice, whereby fluid is mixed within the mixing vessel. 8. The system of claim 7, wherein said pipette tip may be releasably engaged with said at least one nozzle, effective that the pipette tip may be engaged with a nozzle, and may be disengaged from a nozzle. 9. The system of claim 8, wherein application of positive-pressure or suction within said interior passage of the pipette tip does not cause disengagement of the pipette tip. 10. The system of claim 7, wherein said at least one nozzle is movable with respect to the head to which it is operably connected, is movable with respect to the base to which it is operably connected, or both. 11. The system of claim 7, wherein said fluid handling apparatus comprises a component of an automatic sample analysis device, wherein said base is movable with respect to other components of the automatic sample analysis device. 12. The system of claim 7, wherein said engagement region of said interior surface of said mixing vessel comprises a concave feature. 13. The system of claim 12, wherein said concave feature comprises a tapered indentation in a wall or in the bottom of said vessel. 14. The system of claim 13, wherein said tapered indentation comprises a flat bottom configured to engage said tip and occlude said orifice. 15. The system of claim 7, wherein said engagement region of said interior surface of said mixing vessel comprises a convex feature. 16. The system of claim 15, wherein said convex feature comprises a feature extending from a wall or from the bottom of said mixing vessel into the interior of said vessel. 17. The system of claim 16, wherein said feature extending from a wall or from the bottom of said mixing vessel into the interior of said vessel comprises a flat portion. 18. The system of claim 16, wherein at least a portion of said feature extending from a wall or from the bottom of said mixing vessel into the interior of said vessel is configured to extend within said orifice when said pipette tip is pressed onto said wall or bottom of the mixing vessel.
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