Controlled coalescence of gas phase segmented droplets

Patent metadata

Field	Value
Publication number	US-10078038-B2
Application number	US-201615016742-A
Country	US
Kind code	B2
Filing date	Feb 5, 2016
Priority date	Feb 6, 2015
Publication date	Sep 18, 2018
Grant date	Sep 18, 2018

Abstract

A one-dimensional linear array of liquid plugs separated by a gas phase is coalesced by (1) pumping the array through a conduit having a flow restriction of sufficient resistance or (2) a rapid and sudden increase in applied pressure (such as by increasing the flow rate). In this way, the flow of material through the conduit is restricted sufficiently to compress the gas phase into (partial or full) solubility within one or more components of the liquid phase.

First claim

What is claimed is:

1. A method comprising
providing a one-dimensional linear array of liquid plugs in a conduit, said conduit having a continuous, closed-form inner surface having an opening at the proximal and distal ends of the conduit and furthermore containing a restriction comprising a solid phase porous substrate, located at the distal end of the conduit, wherein the array comprises two adjacent liquid plugs separated by a gas phase;
applying a pressure to the proximal end of the conduit advancing the linear array along a flow path toward the restriction;
applying sufficient pressure to the proximal end of the conduit to cause the two adjacent plugs and the gas phase separating them to coalesce into a single plug; and
advancing the coalesced single plug through the restriction.

2. The method of claim 1 , wherein the solid phase porous substrate comprises a packed particle bed, a porous phase coated on the interior walls of the conduit, or a porous monolith.

3. The method of claim 1 , wherein the restriction comprises a liquid chromatography column or a solid phase extraction bed.

4. The method of claim 1 , wherein the adjacent liquid plugs are solutions having different concentrations of solute, and the resulting coalesced plug comprises a concentration gradient of the solute along the length of the conduit.

5. The method of claim 1 , wherein the conduit contains a plurality of arrays, and the arrays in the conduit are separated by spacer plugs, wherein the spacer plugs comprise a liquid immiscible with a solvent found in the liquid plugs of the array.

6. The method of claim 4 , wherein the adjacent fluid plugs comprise water, a water soluble organic solvent, or a combination.

7. The method of claim 5 , wherein the spacer plugs comprise a perfluorocarbon liquid.

8. The method of claim 1 , wherein the adjacent fluid plugs comprise reagents that react with one another when the plugs are coalesced.

9. The method of claim 1 , wherein at least one of the adjacent fluid plugs comprises a solute that is diluted when the adjacent plugs coalesce.

10. The method of claim 1 , wherein the array comprises more than two liquid plugs.

11. A method, comprising:
forming a one dimensional linear array in a conduit by aspirating a plurality of liquids in a desired order into a tube having a diameter sized such that the aspirated liquids form plugs that span the inner diameter of the tube, wherein the plugs are separated from one another by a gas phase plug aspirated between the aspirated liquids;
applying pressure to the linear array to coalesce at least two adjacent plugs and the gas phase separating them in the conduit; and
advancing the coalesced plugs to pass through a separation device.

12. The method of claim 11 , wherein the separation device is a chromatography column or a solid phase extraction bed.

13. The method of claim 12 , wherein the output of the separation device is provided to an electrospray ionization emitter nozzle.

14. The method of claim 11 , wherein the aspirating is performed with a first pump and the advancing is performed with a second pump.

15. The method of claim 14 , wherein the first pump and the second pump are not the same.

16. The method of claim 11 , wherein the linear array comprises a plurality of plugs comprising different levels of the same solute, and wherein the plurality of plugs is coalesced into a single plug having a gradient of solute concentration when the pressure is applied to the linear array.

17. The method according to claim 11 : wherein the plugs in the linear array comprise, in order, a sample droplet, a rinse droplet, an elution droplet, and a second rinse droplet; wherein applying pressure to the linear array coalesces the droplets and the gas phases separating them; and wherein the sample droplet is one that deposits the sample on the substrate, the rinse droplet is one that washes unretained components out of the substrate, the elution droplet is one that elutes the sample from the substrate, and the second rinse droplet is one that reconditions a solid phase porous substrate of the separation device.

18. The method of claim 17 , wherein the sample droplet comprises a fluid sample of biological origin.

19. The method of claim 17 , further comprising providing the output of the solid phase porous substrate to a mass spectrometer.

20. The method of claim 17 , wherein the solid phase porous substrate comprises a packed bed of silica particles.

Assignees

• Univ Michigan Regents

Inventors

• Kennedy Robert T
• Li Qiang
• Valaskovic Gary A
• Chisolm Claire
• Thielen Joanna E

Classifications

• B01D15/424

  Elution mode · CPC title

• G01N30/32

  of pressure or speed (G01N30/36 takes precedence) · CPC title

• G01N2030/009

  Extraction · CPC title

• G01N1/34 Primary

  Purifying; Cleaning {(processes or apparatus for extracting or separating nucleic acids from biological samples C12N15/1003)} · CPC title

• G01N2030/027

  Liquid chromatography · CPC title