Method and apparatus for high-speed microfluidic dispensing using text file control

• US 20040219688A1
• Filed: 01/26/2004
• Published: 11/04/2004
• Est. Priority Date: 01/09/1998
• Status: Abandoned Application

• Current Assignee: BioDot, Inc. (ATS Corp.)
• Original Assignee: BioDot, Inc. (ATS Corp.)
• Inventors: Tisone, Thomas C., Churchill, Carl, Miledi, Rico
• Application Number:
  US10/765,001
• Publication Number:
  US 20040219688A1
• Time in Patent Office: Days
• US Class Current: 436/180
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00351 Means for dispensing and evacuation of reagents
• CPC Class Codes: B01J 2219/00367 capillary
• CPC Class Codes: B01J 2219/00369 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00599 Solution-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00695 Synthesis control routines, e.g. using computer programs
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01L 3/0203 : Burettes, i.e. for withdrawing and redistributing liquids through different conduits
• CPC Class Codes: B01L 3/0265 : using valves to interrupt or meter fluid flow, e.g. using solenoids or metering valves
• CPC Class Codes: B05B 1/02 : designed to produce a jet, spray, or other discharge of particular shape or nature, e.g. in single drops, or having an outlet of particular shapeB05B1/26, B05B1/28, B05B1/34 take precedence
• CPC Class Codes: B05B 1/3053 : the actuating means being a solenoid
• CPC Class Codes: B05B 12/06 : for effecting pulsating flow nozzles, spray head or outlet with means for generating a discharge of pulsating nature B05B1/08
• CPC Class Codes: B05B 13/0221 : characterised by the means for moving or conveying the objects or other work, e.g. conveyor belts B05B13/0207 takes precedence; conveyors in general B65G
• CPC Class Codes: B05B 9/0413 : with reciprocating pumps, e.g. membrane pump, piston pump, bellow pump B05B9/0409 takes precedence
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 50/08 : Liquid phase synthesis, i.e. wherein all library building blocks are in liquid phase or in solution during library creation; Particular methods of cleavage from the liquid support
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 2035/1041 : Ink-jet like dispensers
• CPC Class Codes: G01N 35/1002 : Reagent dispensers
• CPC Class Codes: G01N 35/1016 : Control of the volume dispensed or introduced
• CPC Class Codes: G01N 35/109 : with two horizontal degrees of freedom
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

The invention relates to methods and systems for high-speed precision dispensing and/or aspirating of microfluidic quantities of reagents and other liquids. The operation of the systems is controlled by data accessed from a customized user-defined text file. Advantageously, the use of such text file control allows high-speed precision dispensing of one or more reagents with a wide dynamic range of dispense volumes in complex combinatorial patterns, ratios and arrays onto or into multiple predetermined locations of a desired target or substrate. This is particularly advantageous when a large number of permutations of different reagent and permutations of reagent volume ratios are involved. The systems may be operated in a high frequency modulated mode to further improve accuracy and reliability.

Claims

1. A method for high-speed precise dispensing of microfluidic quantities of a reagent onto or into a target, comprising:

providing a dispenser adapted to form droplets of said reagent;

providing a positive displacement pump in fluid communication with said dispenser for metering precise quantities of said reagent to said dispenser;

providing a controller for controlling and coordinating the volume of said reagent dispensed at predetermined locations on or in said target; and

creating a user-defined text file containing lists of white space delimited numbers defining a dispense pattern that is to be formed on or in said target, said text file being accessible by said controller through a software program such that rapid and accurate dispensing is performed.

2. The method of claim 1, further comprising aspirating said reagent from a receptacle prior to dispensing of said reagent.

3. The method of claim 1, wherein said software program has programmed into it a preset droplet dispense volume which cumulatively determines the total volume dispensed at each of said locations.

4. The method of claim 1, wherein said dispenser comprises a solenoid valve adapted to be opened and closed at a predetermined frequency.

5. The method of claim 4, wherein said valve is operated at a frequency such that its operation is mechanically modulated so that it remains open in oscillation to facilitate ejection of a predetermined volume of said reagent.

6. The method of claim 5, wherein said predetermined volume is in the range from about 1 nL to about 100 nL.

7. The method of claim 5, wherein said predetermined volume is dispensed in the form of multiple droplets of variable size.

8. The method of claim 1, wherein said text file is created by a transformation of data using spreadsheet formulas.

9. The method of claim 1, wherein said white space comprises a tab.

10. The method of claim 1, wherein said white space comprises a carriage return.

11. A method for high speed precise dispensing of a microfluidic quantity of a reagent onto or into a target, comprising the steps of:

positively displacing a precise quantity of said reagent to a dispenser;

forming a volume of said reagent for ejection from said dispenser onto or into said target by opening and closing a solenoid valve at a frequency such that its operation is mechanically modulated so that it remains open in oscillation to facilitate ejection of said volume, said volume being of an integral multiple of said precise quantity and less than or equal to said microfluidic quantity; and

controlling and coordinating said volume of said reagent dispensed at a predetermined location on or in said target.

12. The method of claim 11, wherein said volume is in the range from about 2 nL to about 20 nL.

13. The method of claim 11, wherein said volume is in the range from about 1 nL to about 100 nL.

14. The method of claim 11, wherein said volume is in the range from about 0.1 nL to about 1000 nL.

15. The method of claim 11, wherein said volume is dispensed in the form of multiple droplets.

16. The method of claim 15, wherein said volume is dispensed in the form of multiple droplets of varying size.

17. The method of claim 11, wherein said volume is dispensed in the form of a jet.

18. The method of claim 11, wherein said frequency at which said solenoid valve is operated is about 6000 Hz.

19. The method of claim 11, further comprising aspirating said reagent from a receptacle prior to dispensing of said reagent.

20. The method of claim 11, further comprising creating a user-defined text file to define a reagent dispense pattern or array that is to be formed on or in said target.

21. The method of claim 20, wherein said text file comprises a list of tab-delimited numbers.

22. The method of claim 20, wherein said text file is created by a transformation of raw data in a spreadsheet template.

23. The method of claim 20, wherein said text file is accessible by a controller to control and coordinate said volume of said reagent.

24. The method of claim 11, wherein the volume of said reagent is formed substantially outside said dispenser.