Method and apparatus for acoustically controlling liquid solutions in microfluidic devices

• US 6,948,843 B2
• Filed: 03/20/2001
• Issued: 09/27/2005
• Est. Priority Date: 10/28/1998
• Status: Expired due to Term

• Current Assignee: Covaris, Inc.
• Original Assignee: Covaris, Inc.
• Inventors: Laugharn, James A. Jr., Garrison, Brevard S.
• Primary Examiner(s): SOOHOO, TONY GLEN
• Application Number:
  US09/812,723
• Publication Number:
  US 20020009015A1
• Time in Patent Office: 1,652 Days
• Field of Search: 366/101, 366/108, 366/114, 366/127, 366/DIG.4, 366/347, 366/116, 134/181, 134/1, 422/128
• US Class Current: 366/127
• CPC Class Codes: B01F 2101/23 Mixing of laboratory samples e.g. in preparation of analysing or testing properties of materials
• CPC Class Codes: B01F 2101/44 Mixing of ingredients for microbiology, enzymology, in vitro culture or genetic manipulation
• CPC Class Codes: B01F 2215/0427 Numerical distance values, e.g. separation, position
• 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 2215/045 Numerical flow-rate values
• CPC Class Codes: B01F 2215/0454 Numerical frequency values
• CPC Class Codes: B01F 2215/0468 Numerical pressure values
• CPC Class Codes: B01F 2215/0477 Numerical time values
• CPC Class Codes: B01F 23/40 Mixing liquids with liquids; Emulsifying
• CPC Class Codes: B01F 31/80 Mixing by means of high-frequency vibrations above one kHz, e.g. ultrasonic vibrations
• CPC Class Codes: B01F 31/87 transmitting the vibratory energy by means of a fluid, e.g. by means of air shock waves
• CPC Class Codes: B01F 33/05 Mixers using radiation, e.g. magnetic fields or microwaves to mix the material B01F23/2133, B01F23/238, B01F23/55, B01F33/3031, B01F33/3032 take precedence
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 33/40 Mixers using gas or liquid agitation, e.g. with air supply tubes
• CPC Class Codes: B01F 33/403 for mixing liquids B01F33/402, B01F33/405, B01F33/406 take precedence
• CPC Class Codes: B01F 35/20 Measuring; Control or regulation
• CPC Class Codes: B01F 35/21 Measuring
• CPC Class Codes: B01F 35/2202 Controlling the mixing process by feed-back, i.e. a measured parameter of the mixture is measured, compared with the set-value and the feed values are corrected
• CPC Class Codes: B01F 35/71 Feed mechanisms with proportioning B01F35/80
• CPC Class Codes: B01F 35/712 for feeding fluids
• 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 19/008 : Processes for carrying out reactions under cavitation conditions
• CPC Class Codes: B01J 19/0093 : Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 19/10 : employing sonic or ultrasonic vibrations
• CPC Class Codes: B01J 2219/00308 : interchangeably mounted in racks or blocks
• 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 2219/00486 : by sonication or ultrasonication
• CPC Class Codes: B01J 2219/00495 : Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/00659 : Two-dimensional arrays
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/00783 : Laminate assemblies, i.e. the reactor comprising a stack of plates
• CPC Class Codes: B01J 2219/00889 : Mixing micromixers B01F33/30
• CPC Class Codes: B01L 2400/0433 : vibrational forces
• CPC Class Codes: B01L 2400/0436 : acoustic forces, e.g. surface acoustic waves [SAW]
• 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: B01L 3/5085 : for multiple samples, e.g. microtitration plates
• CPC Class Codes: B01L 7/52 : with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G10K 15/00 : Acoustics not otherwise provided for

Abstract

Acoustic energy is used to control motion in a fluid. According to one embodiment, the invention directs acoustic energy at selected naturally occurring nucleation features to control motion in the fluid. In another embodiment, the invention provides focussed or unfocussed acoustic energy to selectively placed nucleation features to control fluid motion. According to one embodiment, the invention includes an acoustic source, a controller for controlling operation of the acoustic source, and one or more nucleation features located proximate to or in the fluid to be controlled.

Claims

1. A method of imparting motion to a fluid to impart motion to a biological sample located in the fluid, said method comprising,

providing an acoustic source for generating a focused acoustic field, wherein said acoustic source generates a wavetrain substantially converging in a focal zone having a diameter less than or equal to 2 cm, and directing said focused acoustic field to at least one nucleation feature located proximate to the sample located in the fluid to impart motion to the fluid and to the sample located in the fluid proximate to said nucleation feature.

2. The method of claim 1, wherein said step of directing said acoustic field further comprises, adjusting a relative position between said acoustic source and said at least one nucleation feature to bring at least one nucleation feature within a focal zone of said acoustic source.

3. The method of claim 1, wherein said fluid contacts a first surface, and said first surface includes said at least one nucleation feature.

4. The method of claim 3, wherein said at least one nucleation feature includes at least one of a pit, crevice, scratch, groove and ridge in said first surface.

5. The method of claim 3, wherein said fluid has a volume between about 0.1 p1 and about 10 ml.

6. The method of claim 3, wherein said first surface is a surface of a microchamber.

7. The method of claim 1, wherein said fluid is contained in a microchamber.

8. The method of claim 1, wherein said motion imparted to said fluid is of sufficient magnitude to cause a mixing action in said fluid.

9. The method of claim 1 comprising, prior to said step of directing said acoustic field, positioning said at least one nucleation feature proximate to said sample.

10. The method of claim 1, wherein said fluid is contained in a microvessel.

11. An apparatus for imparting motion to a fluid to impart motion to a biological sample located in the fluid, said apparatus comprising,

an acoustic source for generating a focused acoustic field, wherein said acoustic source generates a wavertrain substantially converging in a focal zone having a diameter less than or equal to 2 cm, and

a controller adapted to control operation of said focused acoustic source, wherein said apparatus directs said acoustic field and focuses said field to at least one nucleation feature located proximate to the sample located in the fluid to impart motion to the fluid and to the sample located in the fluid proximate to said nucleation feature.

12. The apparatus of claim 11, wherein said acoustic source is further adapted to provide said direction of said acoustic field, and to provide said acoustic field as a focused acoustic field to said at least one nucleation feature.

13. The apparatus of claim 11 further comprising, a positioning mechanism for adjusting a relative position between said acoustic source and said at least one nucleation feature, to bring said at least one nucleation feature within a focal zone of said acoustic source.

14. The apparatus of claim 11, wherein said fluid contacts a first surface and said at said first surface includes said at least one nucleation feature.

15. The apparatus of claim 14, wherein said first surface is a surface of a microchamber.

16. The apparatus of claim 14, wherein said at least one nucleation feature includes at least one of a pit, crevice, scratch, groove and ridge in said first surface.

17. The apparatus of claim 14, wherein said fluid has a volume between about 0.1 pl and about 10 ml.

18. The apparatus of claim 11, wherein said fluid is contained in a microchamber.

19. The apparatus of claim 11, wherein said motion imparted to said fluid is of sufficient magnitude to cause a mixing action in said fluid.

20. The apparatus of claim 11, wherein said apparatus is further adapted to direct said acoustic field with sufficient specificity to promote mixing of a portion of said fluid proximate to said sample.

21. The apparatus of claim 11, wherein said fluid is contained in a microvessel.