Method of mixing by intermittent centrifugal force

• US 7,147,362 B2
• Filed: 10/15/2003
• Issued: 12/12/2006
• Est. Priority Date: 10/15/2003
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Schembri, Carol T., Caren, Michael P.
• Primary Examiner(s): SORKIN, DAVID L
• Application Number:
  US10/687,276
• Publication Number:
  US 20050083781A1
• Time in Patent Office: 1,154 Days
• Field of Search: 366/131, 366/135, 366/150.1, 366/213, 366/214, 366/220, 366/225, 366/228, 366/235, 366/DIG.1, 366/DIG.3, 435/4, 435/6, 435/287.2, 435/303.3, 422/72, 422/209
• US Class Current: 366/135
• CPC Class Codes: B01F 2215/0431 Numerical size values, e.g. diameter of a hole or conduit, area, volume, length, width, or ratios thereof
• CPC Class Codes: B01F 25/4317 Profiled elements, e.g. profiled blades, bars, pillars, columns or chevrons
• CPC Class Codes: B01F 25/431971 Mounted on the wall
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 35/71 Feed mechanisms with proportioning B01F35/80
• CPC Class Codes: B01F 35/71725 using centrifugal forces
• CPC Class Codes: B01F 35/71805 using valves, gates, orifices or openings
• CPC Class Codes: B01F 35/7547 using valves, gates, orifices or openings
• CPC Class Codes: B01J 2219/00326 Movement by rotation
• CPC Class Codes: B01J 2219/0052 in the shape of elongated tubes
• CPC Class Codes: B01J 2219/00657 One-dimensional arrays
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0806 Standardised forms, e.g. compact disc [CD] format
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 2035/00237 : Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 2035/0449 : using centrifugal transport of liquid
• CPC Class Codes: Y10S 366/01 : Micromixers: continuous laminar flow with laminar boundary mixing in the linear direction parallel to the fluid propagation with or without conduit geometry influences from the pathway
• CPC Class Codes: Y10S 366/03 : Micromixers: variable geometry from the pathway influences mixing/agitation of non-laminar fluid flow

Abstract

An apparatus for mixing fluids comprises a housing having at least a portion of its interior, for example, a channel, with capillary dimensions and at least one structural member in the interior adjacent an end of the channel. The dimensions of and placement of the structural member are sufficient such that intermittent application of centrifugal force to the interior of the housing causes movement of the fluid therein. The housing may comprise a mixing chamber or area that is in fluid communication with the interior. The apparatus may comprise a mechanism adapted to generate centrifugal force within the housing to cause movement of fluid in the interior of the housing without exit of fluid therefrom.

Claims

1. A method for mixing a fluid, said method comprising:

(a) introducing a fluid into a housing of an apparatus, said apparatus comprising;

(i) a housing having an interior comprising an interior channel with capillary dimensions, said interior channel comprising a plurality of biopolymer features arranged in a predetermined manner on an interior surface thereof,

(ii) an opening at a proximal end of said interior channel,

(iii) a chamber at a distal end of said interior channel,

(iv) a structural member in said interior channel adjacent said distal end, the dimensions of and placement of said structural member being sufficient such that intermittent application of centrifugal force to said interior channel causes movement of said fluid between said interior channel and said chamber, and

(v) a mechanism that intermittently generates centrifugal force on the interior of said housing to cause movement of said fluid in said channel, and

(b) generating intermittent centrifugal force to cause repetitive movement of said fluid between said interior channel and said chamber sufficient to cause mixing of said fluid by agitation.

2. A method according to claim 1 wherein said intermittent centrifugal force is generated by rotating said mechanism.

3. A method according to claim 1 wherein said interior channel comprises a linear array of biopolymer features.

4. A method according to claim 3 wherein said linear array is a linear microarray.

5. A method according to claim 4 wherein said linear microarray comprises more than one thousand features.

6. A method according to claim 1 wherein said biopolymer features are polynucleotides or polypeptides.

7. A method according to claim 1 wherein said method is a method for conducting hybridization reactions.

8. A method for conducting chemical reactions, said method comprising:

(a) introducing a fluid sample into a housing of an apparatus, said apparatus comprising;

(i) a housing having an interior comprising an interior channel with capillary dimensions, said interior channel comprising a linear array of biopolymer features arranged in a predetermined manner on an interior surface thereof,

(ii) an opening at a proximal end of said interior channel,

(iii) a chamber at a distal end of said interior channel,

(iv) a structural member in said interior channel adjacent said distal end, the dimensions of and placement of said structural member being sufficient such that intermittent application of centrifugal force to said interior channel causes movement of said fluid between said interior channel and said chamber, and

(v) a mechanism that intermittently generates centrifugal force on the interior of said housing to cause movement of said fluid in said channel, and

(b) incubating said fluid sample in said housing under conditions for carrying out said chemical reactions and during said incubation generating intermittent centrifugal force to cause repetitive movement of said fluid sample between said linear array and said chamber sufficient to cause mixing of said fluid sample by agitation.

9. A method according to claim 8 wherein said intermittent centrifugal force is generated by rotating said housing.

10. A method according to claim 8 wherein said linear array is a linear microarray.

11. A method according to claim 10 wherein said linear microarray comprises more than one thousand features.

12. A method according to claim 8 wherein said biopolymer features are polynucleotides or polypeptides.

13. A method according to claim 8 wherein said method is a method for conducting hybridization reactions.

14. A method for conducting hybridization reactions, said method comprising:

(a) introducing a fluid sample into an opening at a proximal end of a housing comprising a linear microarray of biopolymer features for hybridizing to analytes in said sample, said housing having an interior with internal capillary dimensions, a mixing area separate from said linear array at a distal end of said housing and a structural member in said housing adjacent said distal end, the dimensions of and placement of said structural member being sufficient such that intermittent application of centrifugal force to said housing causes motion of said fluid therein, and

(b) incubating said fluid sample in said housing under conditions for carrying out said hybridization reactions and during said incubation generating intermittent centrifugal force to cause repetitive reciprocal movement of said fluid sample between said linear array and said mixing area such that said fluid sample is mixed by agitation.

15. A method according to claim 14 wherein said intermittent centrifugal force is generated by rotating said housing.

16. A method according to claim 14 further comprising, subsequent to said incubation, increasing said centrifugal force sufficient to cause said fluid to exit said interior.

17. A method according to claim 16 further comprising introducing a wash fluid into said housing and generating intermittent centrifugal force sufficient to cause agitation of said wash fluid but insufficient to cause said wash fluid to exit said housing.

18. A method according to claim 17 further comprising increasing said centrifugal force sufficient to cause said fluid to exit said interior.

19. A method according to claim 14 further comprising examining said linear array for the results of said hybridization reactions.

20. A method according to claim 19 comprising forwarding data representing a result obtained from said examining.

21. A method according to claim 20 wherein the data is transmitted to a remote location.

22. A method according to claim 19 comprising receiving data representing a result of an interrogation obtained by said examining.

23. A method according to claim 14 wherein said housing is part of a microfluidic system.

24. A method according to claim 14 wherein said housing is a channel in a microfluidic system.

25. A method according to claim 14 wherein said features are polynucleotides or polypeptides.

26. A method according to claim 14 wherein said linear microarray comprises more than one thousand features.