ANALYTE DETECTION USING LIQUID CRYSTALS

• US 20110007261A1
• Filed: 04/22/2010
• Published: 01/13/2011
• Est. Priority Date: 04/22/2009
• Status: Active Grant

• Current Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Original Assignee: Wisconsin Alumni Research Foundation (University of Wisconsin System)
• Inventors: Gupta, Jugal, Lin, I-Hsin, Abbott, Nicholas L., Murphy, Christopher J.
• Granted Patent: US 9,080,973 B2
• Time in Patent Office: Days
• US Class Current: 349/199
• CPC Class Codes: G01N 2021/4704 Angular selective
• CPC Class Codes: G01N 2021/4792 Polarisation of scatter light
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 21/21 Polarisation-affecting properties G01N21/19 takes precedence
• CPC Class Codes: G01N 21/49 within a body or fluid
• CPC Class Codes: G01N 21/51 inside a container, e.g. in an ampoule G01N21/53 takes precedence
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/77 by observing the effect on a chemical indicator
• CPC Class Codes: G01N 2400/50 Lipopolysaccharides; LPS
• CPC Class Codes: G01N 33/92 involving lipids, e.g. cholesterol , lipoproteins, or their receptors steroid hormones G01N33/743

Abstract

Devices and methods for using changes in the defects in micrometer sized dispersed liquid crystal domains to detect or quantify analytes in a test sample, including endotoxin lipopolysaccharide (LPS), are disclosed. The dispersed liquid crystal microdomains are exposed to the test sample, and any changes in the number of defects in the liquid crystal microdomains are detected by detecting changes in the anchoring configuration of the microdomains. Such changes in anchoring configuration indicate the presence of analyte in the test sample.

Claims

1. A liquid crystal-based sensor for detecting an analyte in a test sample, comprising:

(a) one or more liquid crystal microdomains that are confined by an interface that generates one or more defects in the liquid crystal microdomains; and

(b) a detector capable of characterizing the orientational order of the liquid crystal microdomains.

2. The liquid crystal-based sensor of claim 1, wherein the microdomains are confined within droplets, within microwells, within capillaries, on surfaces, or within another material.

3. The liquid crystal-based sensor of claim 1 wherein the microdomains have curved interfaces.

4. The liquid crystal-based sensor of claim 1, wherein the liquid crystal microdomains are dispersed and have a minor axis of between about 0.5 μ

m and about 200 μ

m.

5. The liquid crystal-based sensor of claim 2, wherein the liquid crystal microdomains are dispersed liquid crystal droplets within a liquid crystal emulsion.

6. The liquid crystal-based sensor of claim 1, wherein the detector capable of characterizing the orientational order of the liquid crystal microdomains characterizes the orientational order by determining the number of defects in the liquid crystal microdomains, detecting the anchoring configuration of said microdomains, or both.

7. The liquid crystal-based sensor of claim 1, wherein the detector uses light-based detection.

8. The liquid crystal-based sensor of claim 7, wherein the detector is a light-based imaging device.

9. The liquid crystal-based sensor of claim 1, wherein the detector is located on a flow device.

10. The liquid crystal-based sensor of claim 1, wherein a plurality of liquid crystal microdomains are dispersed within a material that is supported on a solid support.

11. The liquid crystal-based sensor of claim 5, wherein the liquid crystal emulsion further comprises an LPS free aqueous phase.

12. The liquid crystal-based sensor of claim 5, further comprising an aqueous test sample in contact with the liquid crystal emulsion.

13. The liquid crystal-based sensor of claim 12, wherein the volume ratio of the aqueous test sample to the liquid crystal contained within the liquid crystal emulsion is greater than or equal to about 100 to 1.

14. The liquid crystal-based sensor of claim 1, wherein at least one of the liquid crystal microdomains have two point defects.

15. The liquid crystal-based sensor of claim 1, wherein the sensor further comprises an analyte in contact with the microdomains, and wherein at least one of the liquid crystal microdomains has one point defect.

17. The liquid crystal-based sensor of claim 1, wherein the liquid crystal microdomains are immobilized.

18. The liquid crystal-based sensor of claim 1, wherein the liquid crystal within the microdomains is 4′

-pentyl-4-cyanobiphenyl (5CB).

16. The liquid crystal-based sensor of claim 16, wherein the analyte is endotoxin lipopolysaccharide (LPS) or lipid A.

19. A method for detecting an analyte in a test sample, comprising the steps of:

(a) providing one or more liquid crystal microdomains having one or more defects;

(b) contacting the microdomains with a test sample; and

(c) using a detector to determine the number of defects in the liquid crystal microdomains, wherein a change in the number of defects indicates the presence of the analyte in the test sample.

20. The method of claim 19, wherein the interface of the liquid crystal microdomain is curved.

21. The method of claim 19, wherein the change in the number of defects in the liquid crystal microdomains is a reduction in the number of defects within the microdomains.

22. The method of claim 19, wherein the number of defects in the liquid crystal microdomains is determined by detecting the anchoring configuration of the microdomains.

23. The method of claim 19, wherein the test sample is an aqueous test sample.

24. The method of claim 19, wherein the analyte is endotoxin lipopolysaccharide (LPS) or lipid A.

25. The method of claim 19, wherein the liquid crystal microdomains have a minor axis of between about 0.5 μ

m and about 200 μ

m.

26. The method of claim 22, wherein the step of using a detector to detect any change in configuration of the liquid crystal microdomains is performed by one or more of the group consisting of optical imaging, fluorescence imaging, optical imaging using polarized light, polarized light microscopy, bright field microscopy, fluorescence microscopy, light scattering measurement, flow cytometry, fluorescence flow cytometry, microelectrophoresis, dielectrophoresis, measurement of electrical capacitance, measurement of magnetic properties, measuring turbidity, detecting optical reflection, detecting transmittance of light, visual inspection, using a plate reader, using microwell plates, and using a cuvette in a detector.

27. The method of claim 19, further comprising the step of using a microfluidic device to deliver the sample to the detector.

28. The method of claim 19, wherein a plurality of dispersed liquid crystal microdomains are provided.

29. The method of claim 28, further comprising the step of using the liquid crystal defect information for the dispersed microdomains to quantify the analyte present in the sample.

30. The method of claim 29, wherein the analyte is endotoxin lipopolysaccharide (LPS) or lipid A.

31. The method of claim 28, wherein the step of providing a plurality of dispersed liquid crystal microdomains comprises providing a liquid crystal in water emulsion wherein the liquid crystal microdomains are liquid crystal droplets.

32. The method of claim 31, wherein the test sample is an aqueous test sample, and the volume ratio of the aqueous test sample to the liquid crystal contained within the liquid crystal emulsion is greater than or equal to about 100 to 1.

33. A method of making a liquid crystal-based sensor for detecting an analyte in a test sample, the method comprising the steps of:

(a) providing a material comprising dispersed liquid crystal microdomains having a minor axis of between about 0.5 μ

m and about 200 μ

m; and

(b) providing a detector capable of detecting the anchoring configuration of the liquid crystal micro domains.

34. The method of claim 33, wherein the step of providing the material comprising dispersed liquid crystal microdomains further comprises immobilizing the dispersed liquid crystal microdomains onto a substrate surface.

35. A liquid crystal-based sensor for detecting endotoxin lipopolysaccharide (LPS) in a test sample, comprising:

(a) a material containing dispersed liquid crystal microdomains having a minor axis of between about 0.5 μ

m and about 200 μ

m; and

(b) a detector capable of detecting the anchoring configuration of the liquid crystal microdomains.

36. A method for detecting endotoxin lipopolysaccharide (LPS) in a test sample, comprising the steps of:

(a) providing a material comprising dispersed liquid crystal microdomains having a minor axis of between about 0.5 μ

m and about 200 μ

m;

(b) contacting the material with an aqueous test sample; and

(c) using a detector to detect the anchoring configuration of the liquid crystal microdomains.