Precision small volume fluid processing apparatus and method

• US 6,218,193 B1
• Filed: 06/30/1998
• Issued: 04/17/2001
• Est. Priority Date: 09/19/1995
• Status: Expired due to Fees

• Current Assignee: Genetools, Inc., University of Washington
• Original Assignee: University of Washington
• Inventors: Meldrum, Deirdre, Seubert, Ronald, Friedman, Neal A., Kraft, Ray
• Primary Examiner(s): LUDLOW, JAN M
• Application Number:
  US09/107,242
• Time in Patent Office: 1,022 Days
• Field of Search: 436/179, 436/180, 436/52, 436/53, 436/54, 422/100, 422/81-82
• US Class Current: 436/180
• CPC Class Codes: B01F 2215/0409 Relationships between different variables defining features or parameters of the apparatus or process
• CPC Class Codes: B01F 31/65 the materials to be mixed being directly submitted to a pulsating movement, e.g. by means of an oscillating piston or air column
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 33/3021 the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets
• CPC Class Codes: B01F 33/30351 using hydrophilic/hydrophobic surfaces
• CPC Class Codes: B01F 35/71 Feed mechanisms with proportioning B01F35/80
• CPC Class Codes: B01F 35/712 for feeding fluids
• CPC Class Codes: B01F 35/714 for feeding predetermined amounts B01F35/88 takes precedence
• CPC Class Codes: B01F 35/7172 using capillary forces
• CPC Class Codes: B01F 35/718 using vacuum, under pressure in a closed receptacle or circuit system
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2200/143 Quality control, feedback systems
• CPC Class Codes: B01L 2300/0838 Capillaries
• CPC Class Codes: B01L 2300/18 Means for temperature control
• CPC Class Codes: B01L 2400/0478 pistons
• CPC Class Codes: B01L 3/02 Burettes; Pipettes
• CPC Class Codes: B01L 3/022 Capillary pipettes, i.e. having very small bore B01L3/0224 - B01L3/0237 take precedence
• CPC Class Codes: B01L 3/0262 using touch-off at substrate or container
• CPC Class Codes: B01L 3/0268 using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: B01L 3/06 Crystallising dishes
• CPC Class Codes: B01L 9/065 : specially adapted for capillary tubes
• CPC Class Codes: G01N 2035/00237 : Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: Y10T 436/118339 : with formation of a segmented stream
• CPC Class Codes: Y10T 436/119163 : with aspirator of claimed structure
• CPC Class Codes: Y10T 436/25625 : Dilution
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

A high precision, small volume fluid processing system employs open ended capillary tubes to meter, aliquot and mix small volumes of sample fluid and reagents. The system has an automatic mechanism for moving the capillary tubes as well as automated sub-systems for incubating and mixing fluids within the capillary tubes.

Claims

1. A method of mixing discrete fluid segments in a constant-diameter, straight capillary tube that has first and second open ends, comprising:

introducing a first fluid volume into the first end of the capillary tube, so as to form a first fluid segment within the tube;

introducing a second fluid volume into the first end of the capillary tube, while simultaneously drawing a partial vacuum at the second end of the capillary tube, so as to move the first fluid segment further into the capillary tube and form a second fluid segment within the capillary tube, separated from the first fluid segment by an air gap; and

oscillating the fluid segments within the capillary tube in opposite directions and at different velocities to cause the fluid segments to mix within the capillary tube.

2. The method of claim 1, wherein the first fluid segment is a sample fluid segment and the second fluid segment is a reagent fluid segment.

3. The method of claim 1, comprising oscillating the fluid segments within the capillary tube by a velocity V₁ in a first direction, and a velocity V₂ in the opposite direction, wherein velocity V₁ is at least approximately three times velocity V₂.

4. The method of claim 1, comprising connecting the capillary tube to a precision linear actuator and operating the precision linear actuator to oscillate the fluid segments within the capillary tube.

5. The method of claim 4, comprising using a computer to operate the precision linear actuator.

6. The method of claim 1, comprising using a hydrophilic capillary tube.

7. The method of claim 6, wherein the first fluid segment is a sample fluid segment and the second fluid segment is a reagent fluid segment.

8. The method of claim 6, comprising oscillating the fluid segments within the capillary tube by a velocity V₁ in a first direction, and a velocity V₂ in the opposite direction, wherein velocity V₁ is approximately three times velocity V₂.

9. The method of claim 6, comprising connecting the capillary tube to a precision linear actuator and operating the precision linear actuator to oscillate the fluid segments within the capillary tube.

10. The method of claim 9, comprising using a computer to operate the precision linear actuator.