ANALYZING CHEMICAL AND BIOLOGICAL SUBSTANCES USING NANO-STRUCTURE BASED SPECTRAL SENSING

• US 20130115717A1
• Filed: 12/21/2012
• Published: 05/09/2013
• Est. Priority Date: 07/13/2011
• Status: Active Grant

• Current Assignee: Excellent Capacity Limited
• Original Assignee: OptoTrace Technologies, Inc.
• Inventors: Guo, Xun, Liu, Chunwei, Wang, Hong, Chang, Huafang, Deng, Anping
• Granted Patent: US 9,274,105 B2
• Time in Patent Office: Days
• US Class Current: 436/501
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: G01N 33/54346 Nanoparticles

Abstract

An integrated chromatography-immunoassay system for integrated chromatography-immunoassay system includes a chromatographic unit that receives labeled nano-structured probes comprising nano particles and antibodies attached to the nano particles, and a test membrane comprising coating antigens. The chromatographic unit allows the labeled nano-structured probes to diffuse there through and into the test membrane, wherein the antibodies on the nano particles are bound to the coating antigens. A laser device emits a laser light to illuminate the labeled nano-structured probes having the antibodies bound to the coating antigens on the test membrane. A spectral analyzer obtains a Raman spectrum from light scattered from the labeled nano-structured probes having the antibodies bound to the coating antigens on the test membrane, and to identify a spectral signature in the Raman spectrum associated with the antibody-antigen pair, which enables detection and identification of the antibody.

Claims

1. An integrated chromatography-immunoassay system, comprising:

a chromatographic unit configured to receive labeled nano-structured probes comprising nano particles and antibodies attached to the nano particles;

a test membrane comprising coating antigens, wherein the chromatographic unit is configured to allow the labeled nano-structured probes to diffuse there through and into the test membrane, wherein the antibodies on the nano particles are bound to the coating antigens;

a laser device configured to emit a laser light to illuminate the labeled nano-structured probes having the antibodies bound to the coating antigens on the test membrane; and

a spectral analyzer configured to obtain a Raman spectrum from light scattered from the labeled nano-structured probes having the antibodies bound to the coating antigens on the test membrane, and to identify a spectral signature in the Raman spectrum associated with the antibody-antigen pair, which enables detection and identification of the antibody.

2. The integrated chromatography-immunoassay system of claim 1, wherein the chromatographic unit is configured to receive a competitive antigen and to allow the competitive antigen to diffuse there through and into the test membrane, wherein the competitive antigen competes with the coating antigens to bind to the antibodies on the nano particles.

3. The integrated chromatography-immunoassay system of claim 1, wherein the labeled nano-structured probes comprises a spectral marker attached to the nano particles or the antibodies.

4. The integrated chromatography-immunoassay system of claim 1, wherein the antigen is selected from a group consisting of clenbuterol, nitrofurans, organic phosphorus, organochlorine, pro terephthalate, a pesticide, a rodenticide, and a veterinary drug.

5. The integrated chromatography-immunoassay system of claim 1, wherein the antigen is selected from a group consisting of melamine, sodium cyclamate, sodium cyclohexylsulfamate, cane sugar, starch, Sudan I, II, III and IV, malachite green, methomidophos, acephate, DDT, DDV, malathion, fenitrothion, deltamethrin, cypermethrin, methyl parathion, phosmet, dimethoate, nitrofuran, furanzolidole, chloramphenicol, chlortetracycline, ciprofloxacin, clenbuterol, and enorfloxacin.

6. The integrated chromatography-immunoassay system of claim 1, wherein the nano particles have an average diameter in a range from 10 nm and 100 nm.

7. The integrated chromatography-immunoassay system of claim 1, wherein the nano particles comprise a material selected from a group consisting of a metal, a metal alloy, an oxide material, silicon, a polymeric material, a magnetic or ferromagnetic material, and a combination thereof, or a material selected from a group consisting of Al, Ag, Au, Cu, Fe, Co, Ni, Cr, Zn, Sn, Pd, Pt, and a combination thereof.

8. The integrated chromatography-immunoassay system of claim 1, wherein the coating antigens comprise clenbuterol, wherein the clenbuterol is bound to an OVA molecule to form an OVA-clenbuterol complex, the OVA-clenbuterol complex bound to the test membrane.

9. A method for identifying an antibody using an integrated chromatography-immunoassay system, comprising:

receiving, by a chromatographic unit, labeled nano-structured probes comprising nano particles and antibodies attached to the nano particles;

allowing the labeled nano-structured probes to diffuse through a test membrane a test membrane comprising coating antigens;

allowing the antibodies on the nano particles to bind to the coating antigens;

illuminating the labeled nano-structured probes having the antibodies bound to the coating antigens on the test membrane by a laser light;

obtaining a Raman spectrum from light scattered with a spectral analyzer from the labeled nano-structured probes having the antibodies bound to the coating antigens on the test membrane; and

identifying a spectral signature in the Raman spectrum associated with the antibody-antigen pair, which enables detection and identification of the antibody.

10. The method of claim 9, further comprising:

receiving a competitive antigen by the chromatographic unit; and

allowing the competitive antigen to diffuse through the test membrane, wherein the competitive antigen is configured to compete with the coating antigens to bind to the antibodies on the nano particles.

11. The method of claim 9, wherein the labeled nano-structured probes comprises a spectral marker attached to the nano particles or the antibodies.

12. The method of claim 9, wherein the antigen is selected from a group consisting of clenbuterol, nitrofurans, organic phosphorus, organochlorine, pro terephthalate, a pesticide, a rodenticide, and a veterinary drug.

13. The method of claim 9, wherein the antigen is selected from a group consisting of melamine, sodium cyclamate, sodium cyclohexylsulfamate, cane sugar, starch, Sudan I, II, III and IV, malachite green, methomidophos, acephate, DDT, DDV, malathion, fenitrothion, deltamethrin, cypermethrin, methyl parathion, phosmet, dimethoate, nitrofuran, furanzolidole, chloramphenicol, chlortetracycline, ciprofloxacin, clenbuterol, and enorfloxacin.

14. The method of claim 9, wherein the nano particles have an average diameter in a range from 10 nm and 100 nm.

15. The method of claim 9, wherein the nano particles is selected from a group consisting of a material selected from a group consisting of a metal, a metal alloy, an oxide material, silicon, a polymeric material, a magnetic or ferromagnetic material, and a combination thereof, or comprises a material selected from a group consisting of Al, Ag, Au, Cu, Fe, Co, Ni, Cr, Zn, Sn, Pd, Pt, and a combination thereof.

16. The method of claim 9, wherein the coating antigens comprise clenbuterol, wherein the clenbuterol is bound to an OVA molecule to form an OVA-clenbuterol complex, the OVA-clenbuterol complex bound to the test membrane.

17. A method for substance identification, comprising:

allowing an antibody to be adsorbed to a nano surface structure;

introducing an unknown antigen to the nano surface structure to allow the unknown antigen to bind with antibody on the nano surface structure;

illuminating, by a laser beam, the bound unknown antigen and antibody on the nano surface structure;

collecting light scattered by the bound unknown antigen and antibody on the nano surface structure;

obtaining a Raman spectrum from the light scattered by the bound unknown antigen and antibody on the nano surface structure;

finding a spectral signature associated with the bound unknown antigen and antibody in the Raman spectrum; and

identifying the unknown antigen as an antigen that matches the antibody on the nano surface structure based on the spectral signature.

18. The method of claim 17, wherein the antigen is selected from the group consisting of clenbuterol, nitrofurans, organic phosphorus, organochlorine, pro terephthalate, a pesticide, a rodenticide, a substance in a veterinary drug, an arsenic compound, and a cyanide.

19. The method of claim 17, wherein the antigen is selected from the group consisting of melamine, sodium cyclamate, sodium cyclohexylsulfamate, cane sugar, starch, nitrite, nitrate, Sudan I, II, III and IV, malachite green, methomidophos, acephate, DDT, DDV, malathion, fenitrothion, deltamethrin, cypermethrin, methyl parathion, phosmet, dimethoate, nitrofuran, furanzolidole, chloramphenicol, chlortetracycline, ciprofloxacin, clenbuterol, and enorfloxacin.

20. The method of claim 17, further comprising:

diagnosing a disease in the person based on the identification of the unknown antigen associated with the disease.

21. The method of claim 20, wherein the reagent comprises a body fluid obtained from a person.

22. The method of claim 20, wherein the disease is selected from the group consisting of a cancer, asthma, allergy, liver cirrhosis, a failing kidney, leukemia, Alzheimer'"'"'s disease, Parkinson disease, diabetes, smoking addiction, arthritis, a cardiovascular disease, SARS, a flu, and human immunodeficiency virus (HIV).

23. The method of claim 17, wherein the unknown antigen comprises an illicit drug substance selected from a group consisting of heroin, methamphetamine, cocaine, caffeine, morphine, codeine, amphetamine, ephedrine, papaverine, narcotine, Ketamine, and MDMA.

24. The method of claim 17, wherein the unknown antigen comprises a protein carrier and the molecule of an unknown substance bound to the protein carrier, wherein the identification of the protein carrier leads to the identification of the unknown substance.

25. The method of claim 24, wherein the unknown substance comprises Ketamine or fluoroacetamide.

26. The method of claim 17, wherein the unknown antigen is extracted from a food product.

27. The method of claim 17, further comprising applying an electrical field, a magnetic field, or an electro-magnetic field to the nano surface structures when the light scattered by each of the nano surface structures is collected.

28. The method of claim 17, wherein the nano surface structure comprises nano particles having an average dimension in a range from about 1 nm to about 1000 nm.

29. The method of claim 28, wherein the nano particles comprise a material selected from a group consisting of a metal, a metal alloy, an oxide material, silicon, a polymeric material, a magnetic or ferromagnetic material, and a combination thereof, or a material selected from a group consisting of Al, Ag, Au, Cu, Fe, Co, Ni, Cr, Zn, Sn, Pd, Pt, and a combination thereof.

30. The method of claim 17, wherein the nano surface structure are formed on a substrate.

31. The method of claim 30, wherein the nano surface structures comprise protrusions or columns formed on an upper surface of the substrate, wherein the neighboring protrusions or columns have average distances in a range from 10 nanometers to 1000 nanometers.

32. The method of claim 30, wherein the nano surface structures comprise recesses or holes formed in an upper surface of the substrate, wherein the neighboring recesses or holes have average distances in a range from 10 nanometers to 1000 nanometers.

33. A method for substance identification, comprising:

applying a pre-treatment chemical or biological material to a nano surface structure;

introducing a reagent containing an unknown substance to the nano surface structure to allow molecules of the unknown substance to adsorb to the nano surface structure with the assistance of the pre-treatment chemical or biological material;

illuminating the nano surface structure adsorbed with molecules of the unknown substance by a laser beam;

collecting light scattered by the nano surface structure adsorbed with molecules of the unknown substance;

obtaining a Raman spectrum from the light scattered by the nano surface adsorbed with molecules of the unknown substance;

finding a spectral signature associated with the unknown substance in the Raman spectra; and

identifying the unknown substance in the reagent using the spectral signature.

34. The method of claim 33, wherein the antigen comprises a protein carrier and the molecule of an unknown substance bound to the protein carrier, the method further comprising:

identifying the protein carrier based on the spectral signature, wherein the unknown substance is identified based on the identification of the protein carrier.

35. The method of claim 34, wherein the unknown substance comprises Ketamine or fluoroacetamide.

36. The method of claim 33, wherein the pre-treatment chemical or biological material comprises an antibody configured to adsorb to the surfaces of the nano surface structure, wherein the unknown substance is an antigen that matches the antibody, wherein the spectral signature is associated with antigen-antibody pair adsorbed to the nano surface structure.

37. The method of claim 33, wherein the pre-treatment chemical or biological material comprises an antigen configured to adsorb to the surfaces of the nano surface structure, wherein the unknown substance is an antibody that matches the antigen, wherein the spectral signature is associated with antigen-antibody pair adsorbed to the nano surface structure.

38. The method of claim 33, wherein the nano surface structures comprise nano particles having an average dimension in a range from about 1 nm to about 1000 nm, or nano structures formed on a substrate.