Ionic liquid apparatus and method for biological samples

• US 7,572,409 B2
• Filed: 05/23/2003
• Issued: 08/11/2009
• Est. Priority Date: 05/23/2003
• Status: Active Grant

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Inventors: Bryning, Zbigniew T., Liu, Timothy Z.
• Primary Examiner(s): FORMAN, BETTY J
• Application Number:
  US10/444,848
• Publication Number:
  US 20040234966A1
• Time in Patent Office: 2,272 Days
• Field of Search: None
• US Class Current: 422/68.1
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0418 electro-osmotic flow [EOF]
• CPC Class Codes: B01L 2400/0421 electrophoretic flow
• 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 3/502784 specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: G01N 27/44704 Details; Accessories
• CPC Class Codes: G01N 27/44747 Composition of gel or of carrier mixture

Abstract

Apparatus and method for handling biological samples. Segments of ionic liquid can provide voltage across segments of immiscible liquid to concentrate or separate charged species in the biological samples. Reactants in biological samples can be contacted and reacted in segments of immiscible liquid.

Claims

1. An apparatus for handling biological samples, comprising:

a channel; and

a plurality of liquid segments in said channel, wherein said plurality of segments comprises an immiscible liquid segment between ionic liquid segments, wherein the immiscible liquid segment comprises the biological sample and the ionic liquid segment comprises a liquid salt.

2. The apparatus of claim 1, wherein a voltage is applied across said immiscible liquid segment.

3. The apparatus of claim 2, wherein said immiscible liquid segment comprises a separation polymer.

4. The apparatus of claim 1, wherein said biological sample is adapted for at least one of PCR, ligase chain reaction, antibody binding reaction, oligonucleotide ligations assay, and hybridization assay.

5. The apparatus of claim 1, wherein said channel is a capillary or a microchannel.

6. The apparatus of claim 1, wherein said immiscible liquid segment comprises at least one of aqueous and non-polar organic solvents.

7. An apparatus for handling biological samples, comprising:

a plurality of segments comprising an immiscible liquid segment between ionic liquid segments, wherein voltage is applied across said immiscible liquid segment to provide electrophoresis, and wherein the immiscible liquid segment comprises the biological sample and the ionic liquid segment comprises a liquid salt.

8. The apparatus of claim 7, wherein said voltage is applied between a first electrode in a first segment of ionic liquid and to a second electrode in a second segment of ionic liquid.

9. The apparatus of claim 7, wherein said biological sample is adapted for at least one of PCR, ligase chain reaction, antibody binding reaction, oligonucleotide ligations assay, and hybridization assay.

10. The apparatus of claim 7, wherein said immiscible liquid segment comprises a separation polymer.

11. The apparatus of claim 7, further comprising a channel, wherein said channel is a capillary or a microchannel.

12. The apparatus of claim 7, wherein said immiscible liquid segment comprises at least one of aqueous and non-polar organic solvents.

13. An apparatus for handling biological samples, comprising:

a plurality of segments comprising an ionic liquid segment between immiscible liquid segments, wherein a voltage is applied across said ionic liquid segment, wherein said voltage is adapted to break said ionic liquid segment and contact said immiscible liquid segments, and wherein the immiscible liquid segment comprises the biological sample and the ionic liquid segment comprises a liquid salt.

14. The apparatus of claim 13, wherein said immiscible liquid segments comprise reactants.

15. The apparatus of claim 14, wherein said reactants are adapted for at least one of PCR, ligase chain reaction, antibody binding reaction, oligonucleotide ligations assay, and hybridization assay.

16. The apparatus of claim 13, wherein said channel is a capillary or a microchannel.

17. The apparatus of claim 13, wherein said immiscible liquid segment comprises at least one of aqueous and non-polar organic solvents.

18. A method for handling a biological sample comprising:

providing a plurality of liquid segments in a channel, the plurality of liquid segments comprising an immiscible liquid segment between ionic liquid segments wherein the immiscible liquid segment comprises the biological sample and the ionic liquid segments comprise a liquid salt; and

providing a voltage across said immiscible liquid segment.

19. The method of claim 18, wherein said biological sample is adapted for at least one of PCR, ligase chain reaction, antibody binding reaction, oligonucleotide ligation assay, and hybridization assay.

20. The method of claim 18, wherein said immiscible liquid segment comprises at least one of aqueous and non-polar organic solvents.

21. The method of claim 18, further comprising concentrating a charged species in said immiscible liquid.

22. The method of claim 21, further comprising detecting the concentrated charged species.

23. The method of claim 18, further comprising separating a charged species in said immiscible liquid.

24. The method of claim 23, further comprising detecting the separated charged species.

25. A method for handling biological samples comprising:

providing an ionic liquid segment between a first immiscible liquid segment and a second immiscible liquid segment in a channel, wherein said first immiscible liquid segment comprises a biological sample and said second immiscible liquid segment comprises a reactant, and said ionic liquid segment comprises a liquid salt;

providing a voltage across said ionic liquid segment;

breaking said ionic liquid segment; and

contacting said biological sample and said reactant.

26. The method of claim 25, wherein said biological sample and said reactant are adapted for at least one of PCR, ligase chain reaction, antibody binding reaction, oligonucleotide ligation assay, and hybridization assay.

27. The method of claim 25, wherein said immiscible liquid segment comprises at least one of aqueous and non-polar organic solvents.

28. The method of claim 25, further comprising detecting reaction products by at least one of absorbance, fluorescence spectroscopy, Raman spectroscopy, reflectance, and colorimetry.

29. A method for forming a plurality of segments of biological samples comprising:

providing a channel comprising an inlet;

positioning said inlet in a container comprising an immiscible material layer and an ionic liquid layer, wherein said layers are immiscible;

coating said channel with said ionic liquid; and

aspirating an immiscible liquid segment into said inlet, thereby forming a plurality of liquid segments comprising an immiscible liquid segment between two segments of ionic liquid wherein the immiscible liquid segment comprises a biological sample and the ionic liquid segments comprise liquid salts.

30. The method according to claim 29, wherein said coating comprises positioning said inlet in said ionic liquid layer and suctioning ionic liquid.

31. The method according to claim 30, wherein said aspirating comprises positioning said inlet from said ionic liquid layer to said immiscible material layer and suctioning immiscible material.