Flow focusing method and system for forming concentrated volumes of microbeads, and microbeads formed further thereto

• US 8,551,763 B2
• Filed: 10/10/2008
• Issued: 10/08/2013
• Est. Priority Date: 10/12/2007
• Status: Expired due to Fees

• Current Assignee: Fio Corporation
• Original Assignee: Fio Corporation
• Inventors: Fournier-Bidoz, Sebastien, Chan, Warren Che Wor
• Primary Examiner(s): Haq, Shafiqul
• Application Number:
  US12/682,710
• Publication Number:
  US 20110081643A1
• Time in Patent Office: 1,824 Days
• Field of Search: None
• US Class Current: 435/286.5
• CPC Class Codes: B01F 23/41 Emulsifying
• CPC Class Codes: B01F 33/3011 using a sheathing stream of a fluid surrounding a central stream of a different fluid, e.g. for reducing the cross-section of the central stream or to produce droplets from the central stream
• CPC Class Codes: B01F 33/453 using supported or suspended stirring elements
• CPC Class Codes: B01F 33/4534 using a rod for supporting the stirring element, e.g. stirrer sliding on a rod or mounted on a rod sliding in a tube
• CPC Class Codes: B01J 13/04 by physical processes, e.g. drying, spraying
• CPC Class Codes: B29C 48/2552 provided in the feeding, melting, plasticising or pumping zone, e.g. screw, barrel, gear-pump or ram
• CPC Class Codes: C08J 3/14 by precipitation from solutions C08J3/122 takes precedence
• CPC Class Codes: C08J 3/21 the polymer being premixed with a liquid phase
• CPC Class Codes: C12Q 1/701 Specific hybridization probes
• CPC Class Codes: C12Q 1/706 for hepatitis

Abstract

In a method and system for forming concentrated volumes of microbeads, a polymer solution and/or suspension includes a polymer dissolved and/or dispersed in a medium. Streams of a focusing fluid and of the polymer solution and/or suspension flow towards a fluid bath, and into intersection with one another, so &s to focus the polymer solution and/or suspension. The polymer solution and/or suspension stream forms microbeads in the fluid bath. Some of the focusing fluid is drawn from the fluid bath, so as to concentrate the microbeads in die fluid bath. The system includes a flow focusing apparatus and a liquid-containing cell. The focusing apparatus includes polymer and focusing nozzles. The cell contains the fluid bath and has an outlet port, through which the focusing fluid is drawn from the fluid bath.

Claims

1. A method of forming one or more concentrated volumes of microbeads, the method comprising the steps of:

(a) flowing, a focused stream of a polymer solution, polymer suspension, or polymer solution and suspension towards a fluid bath, with the polymer solution, polymer suspension, or polymer solution and suspension comprising a polymer dissolved, dispersed, or dissolved and dispersed in a medium;

(b) flowing a focusing stream of a focusing fluid towards the fluid bath, and into intersection with the focused stream;

(b.1) after step (b), maintaining the fluid bath under stirring so that the focusing fluid and the polymer solution continue to be mixed and intermingled;

(c) after step (b), flowing the focusing stream and the focused stream into the fluid bath and allowing the microbeads to, thus, form and solidify in the fluid bath;

(d) flowing a volume of the focusing fluid from the fluid bath while leaving the microbeads in the fluid bath, so as to concentrate the microbeads in the fluid bath; and

(e) recycling at least part of the volume of the focusing fluid, flowing from the fluid bath in step (d), as at least part of the focusing stream flowing into intersection with the focused stream in step (b).

2. The method according to claim 1, wherein in step (d), the fluid bath is controlled so as to be maintained at a substantially constant liquid level.

3. The method according to claim 2, wherein the substantially constant liquid level is maintained by balancing respective flow rates for the focused stream in step (a), the focusing stream in step (b), and the focusing fluid in step (d).

4. The method according to claim 1, wherein in step (d), the volume of the focusing fluid flows through one or more filters.

5. The method according to claim 4, wherein in step (d), the filters retain the microbeads in the fluid bath.

6. The method according to claim 4, wherein in step (d), the filters retain a substantially monodisperse set of the microbeads in the fluid bath.

7. The method according to claim 4, wherein in step (d), the filters divide the microbeads into one or more collections of microbeads, with each of the collections including a respectively monodisperse set of the microbeads.

8. The method according to claim 1, wherein at least one of steps (a) and (b) is performed within an interior chamber of a flow focusing body.

9. The method according to claim 8, wherein steps (a) and (b) are both performed within the interior chamber of the flow focusing body, with an outlet portion of the flow focusing body being located below a liquid level of the fluid bath, and wherein in step (c), the focusing stream and the focused stream flow out from the outlet portion of the flow focusing body.

10. The method according to claim 9, wherein in step (b), the focused stream is focused by the focusing fluid, and wherein in step (c), the focusing stream and the focused stream flow out from the outlet portion as a single flow stream.

11. The method according to claim 10, wherein in step (c), the focusing stream substantially surrounds the focused stream in the single flow stream.

12. The method according to claim 1, further comprising a preliminary step, before step (a), of providing the fluid bath within a sealed liquid-containing cell.

13. The method according to claim 12, wherein at least one of steps (a) through (c) is performed within the liquid-containing cell.

14. The method according to claim 12, wherein in the preliminary step, the liquid-containing cell additionally contains a volume of a gas at a predetermined pressure.

15. The method according to claim 14, wherein in the preliminary step, a gas pressure source pressurizes the gas, via an inlet valve, in the sealed liquid-containing cell.

16. The method according to claim 14, further comprising step (c.1), after the preliminary step, of releasing a portion of the gas or the fluid bath, via a pressure safety valve, when the pressure exceeds a predetermined maximum safety pressure for the sealed liquid-containing cell.

17. The method according to claim 14, wherein the gas comprises an inert gas.

18. The method according to claim 14, wherein the pressure of the gas in the preliminary step is predetermined, in balance with respective flow rates for the focused stream in step (a) and the focusing stream in step (b), to maintain the fluid bath at a substantially constant liquid level.

19. The method according to claim 1, wherein in step (b.1), a stirring bar maintains the fluid bath under stirring, and wherein the stirring bar comprises an electric stirring bar or a magnetic stirring bar.

20. The method according to claim 1, further comprising step (d.1), after step (d), of recovering solidified microbeads from the fluid bath.

21. The method according to claim 1, wherein in step (a), the medium comprises an organic solvent.

22. The method according to claim 21, wherein the organic solvent comprises chloroform or dichloromethane.

23. The method according to claim 1, wherein in step (a), the polymer is substantially hydrophobic.

24. The method according to claim 1, wherein in step (a), the polymer comprises a polystyrene powder or a derivative thereof.

25. The method according to claim 1, wherein in step (b), the focusing fluid comprises water.

26. The method according to claim 1, wherein in step (a), the polymer solution further comprises particles dissolved, dispersed, or dissolved and dispersed in the medium, and wherein in step (c), each of the microbeads binds an identifiable set of the particles.

27. The method according to claim 26, wherein in step (a), the particles comprise fluorophores.

28. The method according to claim 26, wherein in step (a), the particles comprise nanoparticles.

29. The method according to claim 28, wherein the nanoparticles comprise semiconductor nanoparticles, magnetic nanoparticles, metallic conductor nanoparticles, metal oxide nanoparticles, fluorescent nanoparticles, or phosphorescent nanoparticles.

30. The method according to claim 26, wherein in step (a), the particles comprise quantum dots.

31. The method according to claim 26, wherein in step (a), the particles comprise a combination of quantum dots and magnetic nanoparticles.

32. The method according to claim 1, wherein in step (a), the polymer solution, polymer suspension, or polymer solution and suspension has a concentration of about 0.04 by weight-weight percentage (4 wt %).