Sample droplet generation from segmented fluid flow and related devices and methods

Patent metadata

Field	Value
Publication number	US-9543137-B2
Application number	US-201514883990-A
Country	US
Kind code	B2
Filing date	Oct 15, 2015
Priority date	Dec 12, 2014
Publication date	Jan 10, 2017
Grant date	Jan 10, 2017

Abstract

A sample droplet generator transforms a segmented array of sample material into a continuous stream of droplets containing analytes. The droplets may serve as a sample source for a wide range of detectors and analytical instruments. As one example, the droplets may be introduced into an ion source of a spectrometer that measures ions produced from the droplets or photons emitted from the droplets.

First claim

What is claimed is:

1. A sample introduction device, comprising:
a segmented sample array source configured for flowing a linear segmented sample array comprising a plurality of first plugs alternately separated by a plurality of second plugs, wherein the first plugs comprise a first fluid and analytes and the second plugs comprise a second fluid different from the first fluid; and
a sample droplet generator configured for generating a stream of droplets from the segmented sample array wherein the droplets comprise the analytes, the sample droplet generator comprising:
a first tube comprising a first tube inlet communicating with the segmented sample array source and a first tube outlet, the first tube defining a sample path; and
a second tube surrounding the first tube and comprising a second tube outlet, wherein the second tube defines a gas path between the first tube and the second tube leading to the second tube outlet, and the second tube outlet is positioned such that the sample path merges into the gas path, and
wherein the first tube and the second tube extend along a longitudinal axis, and the second tube outlet is positioned at a downstream axial distance from the first tube outlet.

2. The sample introduction device of claim 1 , wherein the segmented sample array source comprises a sample container having a size effective for maintaining the segmented sample array in a linear arrangement.

3. The sample introduction device of claim 1 , wherein the segmented sample array source comprises a segmented array forming device.

4. The sample introduction device of claim 3 , wherein the segmented array forming device comprises a feature selected from the group consisting of:
a supply conduit for flowing the first fluid from a reservoir;
a sample processing device communicating with the supply conduit;
a fluidic junction, a first supply conduit for conducting the first fluid to the fluidic junction, and a second supply conduit for conducting the second fluid to the fluidic junction;
a first pump configured for flowing the first fluid, and a second pump configured for flowing the second fluid; and
an aspiration tube, and one or more reservoirs containing the first fluid, the second fluid, or both the first fluid and the second fluid, wherein the aspiration tube is selectively movable into the one or more reservoirs.

5. An atmospheric pressure ionization (API) source, comprising:
the sample introduction device of claim 1 ;
a chamber communicating with the second tube outlet; and
an ionization device configured for ionizing analytes from droplets emitted from the second tube outlet into the chamber at atmospheric pressure.

6. A sample analysis system, comprising:
the API source of claim 5 ; and
an analytical instrument interfaced with the chamber and configured for acquiring data from ions or photons produced by the API source.

7. A sample analysis system, comprising:
the sample introduction device of claim 1 ; and
an analytical instrument configured for acquiring data from the analytes or from ions or photons produced from the analytes.

8. The sample analysis system of claim 7 , comprising a chamber positioned to receive droplets emitted from the sample introduction device, and optics between the chamber and the analytical instrument.

9. A method for generating droplets for analysis, the method comprising:
flowing a linear segmented sample array along a sample path through a first tube and out from a first tube outlet, the linear segmented sample array comprising a plurality of first plugs alternately separated by a plurality of second plugs, wherein the first plugs comprise a first fluid and analytes and the second plugs comprise a second fluid different from the first fluid;
flowing a gas along a gas path between the first tube and a second tube surrounding the first tube, and toward a second tube outlet, wherein the sample path merges into the gas path downstream of the first tube outlet such that at least the first plugs are broken into droplets comprising the analytes, and wherein the first tube and the second tube extend along a longitudinal axis, and the second tube outlet is positioned at a downstream axial distance from the first tube outlet; and
emitting a stream of the droplets from the second tube outlet.

10. The method of claim 9 , wherein the first fluid and the second fluid have a configuration selected from the group consisting of:
the first fluid and second fluid are substantially immiscible;
one of the first fluid and the second fluid comprises an aqueous medium and other of the first fluid and the second fluid comprises an organic medium; and
the first fluid comprises an aqueous medium and the second fluid comprises a fluorocarbon, an oil, or a gas.

11. The method of claim 9 , comprising, before flowing the linear segmented sample array through the first tube, flowing the linear segmented sample array into a sample container, and further comprising at least one of: storing the sample container for a period of time; transporting the sample container to the first tube; or coupling the sample container with the first tube.

12. The method of claim 9 , comprising forming the linear segmented sample array.

13. The method of claim 12 , comprising, before or after forming the linear segmented sample array, carrying out a sample process on the first fluid selected from the group consisting of:
mixing the first fluid with another fluid;
adding a reagent to the first fluid;
carrying out an analytical separation technique on the first fluid;
diluting the first fluid;
carrying out dialysis on the first fluid;
lysing a cell contained in the first fluid;
filtering the first fluid;
transferring heat to or from the first fluid; and
a combination of two or more of the foregoing.

14. The method of claim 12 , wherein forming the linear segmented sample array comprises a step selected from the group consisting of:
flowing the first fluid from a reservoir;
flowing the first fluid and the second fluid into a fluid junction, and flowing the linear segmented sample array out from the fluid junction;
flowing at least one of the first fluid and the second fluid is done according to a pulse sequence; and
alternately inserting an aspiration tube into a container and aspirating a quantity of at least one of the first fluid and the second fluid from the container, and removing the aspiration tube from the container.

15. The method of claim 9 , comprising, before flowing the linear segmented sample array through the first tube, performing a step selected from the group consisting of:
carrying out liquid-liquid extraction on the linear segmented sample array;
flowing the linear segmented sample array through a transfer conduit for a period of time sufficient for a component contained in the first plugs or the second plugs to be transferred into adjacent plugs; and
flowing the linear segmented sample array through a transfer conduit for a period of time sufficient for the first plugs to at least partially merge with the second plugs.

16. A method for ionizing a sample, comprising:
generating droplets according to the method of claim 9 ;
emitting the droplets into a chamber at about atmospheric pressure; and
ionizing the analytes contained in the droplets.

17. A method for analyzing a sample, comprising:
ionizing analytes according to the method of claim 16 to produce ions; and
measuring an attribute of the ions.

18. A method for atomizing a sample, comprising:
generating droplets according to the method

Assignees

• Agilent Technologies Inc

Inventors

• Apffel James Alexander
• Schleifer Arthur

Classifications

• G01N21/66

  electrically excited, e.g. electroluminescence · CPC title

• H01J49/10 Primary

  Ion sources; Ion guns · CPC title

• G01N1/44

  Sample treatment involving radiation, e.g. heat · CPC title

• G01N35/085

  Flow Injection Analysis · CPC title

• H01J49/0431

  for liquid samples (interfaces to liquid chromatographs G01N30/7233) · CPC title