Precision small volume fluid processing apparatus

• US 5,785,926 A
• Filed: 09/19/1995
• Issued: 07/28/1998
• Est. Priority Date: 09/19/1995
• Status: Expired due to Fees

• Current Assignee: Genetools, Inc., University of Washington, Washington University In St Louis
• Original Assignee: Genetools, Inc., University of Washington
• Inventors: Seubert, Ronald, Wiktor, Peter, Olson, Maynard V., Meldrum, Deirdre, Hannaford, Blake, Snow, Donald B., Friedman, Neal A., Kraft, Ray
• Primary Examiner(s): LUDLOW, JAN M
• Application Number:
  US08/531,215
• Time in Patent Office: 1,043 Days
• Field of Search: 422/100, 422/82, 422/99, 435/287.1, 435/287.2, 435/289.1, 435/303.1, 73/864.11, 73/864.14, 73/864.22, 73/864.24, 73/864.25
• US Class Current: 422/518
• 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 high precision, small volume fluid processing system, comprising:

a sample fluid station;

a reagent fluid dispensing device;

a sample fluid handling device having a single open ended capillary tube fluidly connected to a precision linear actuator;

monitoring means for determining position information of ends of a fluid segment in the capillary tube;

positioning means for precisely positioning the fluid sample handling device in a reference plane with respect to the reagent fluid dispensing device and the sample fluid station; and

,

control means, operatively connected to the linear actuator and the positioning means, for positioning the capillary tube and operating the actuator to receive within the capillary tube both a precisely metered volume of sample fluid from the sample fluid station and at least one precisely metered volume of at least one reagent fluid from the reagent dispensing device.

2. The system of claim 1, wherein the linear actuator has a computer controllable motor rotatably connected to a precision lead screw, and wherein the capillary tube is removably and sealingly connected to the lead screw through an adaptor sized to removably receive the capillary tube in a friction fit.

3. The system of claim 2, wherein the adaptor has a housing defining a dead air volume and a cap portion having a stop ring and an "O" ring for sealingly receiving one of the open ends of the capillary tube, the cap portion further having a radially directed pressure relief vent.

4. The system of claim 1, wherein the monitoring means includes a light emitter/detector array having a plurality of sequentially arranged optical elements proximal to the capillary tube.

5. The system of claim 4, wherein the emitter/detector array has a plurality of charge coupled devices thereon.

6. The system of claim 1, wherein the capillary tube has an exterior, substantially transparent resistive coating thereon, and wherein the system includes controlled voltage generating means for causing a current to flow through the coating to heat the tube and wherein the system includes an air flow means, cooperatively interconnected with the controlled voltage generating means for incubating the capillary tube in a controlled manner.

7. The system of claim 6, wherein the coating is a layer of resistive material.

8. The system of claim 1, wherein the capillary tube has an enlarged diameter central interior portion defining a mixing chamber.

9. The system of claim 1, wherein the reagent fluid dispensing device is a ballistic fluid dispensing device.

10. The system of claim 1, wherein the reagent fluid dispensing device is a reagent fluid handling device having an open ended dispensing capillary tube fluidly connected to a precision linear actuator, wherein the linear actuator has a computer controllable stepper motor rotatably connected to a precision lead screw, and wherein the dispensing capillary tube is connected to the lead screw through an adaptor.

11. A high precision, small volume fluid aliquoting system, comprising:

a sample fluid station;

a receiving capillary tube having at least one open end;

a sample fluid handling device having a single aliquoting capillary tube having one end fluidly connected to a precision linear actuator, including control means for aspirating and handling a precisely metered volume of sample fluid through an open end of the aliquoting capillary tube; and

,

positioning means cooperatively coupled with the control means for precisely positioning the fluid sample handling device in a reference plane with respect to the sample fluid station and the receiving capillary tube so that the open ends of the receiving and aliquoting tubes can be precisely positioned adjacent one another for transferring a precise volume of sample fluid from the aliquoting capillary tube to the receiving capillary tube.

12. The system of claim 11, wherein the system includes a monitoring device for determining position information of ends of a fluid segment in the aliquoting capillary tube, and wherein the linear actuator has a computer controllable motor rotatably connected to a precision lead screw, and wherein the aliquoting capillary tube is connected to the lead screw through an adaptor.

13. The system of claim 12, wherein the adaptor has a housing defining a dead air volume and cap portion having a stop ring and an "O" ring for sealingly receiving one of the open ends of the aliquoting capillary tube, the cap portion further having a radially directed pressure relief vent.