Fluorescent sensor based on two fluorescent moieties, one of which is a semiconductor nanocrystal, and methods of using and making

• US 8,313,957 B2
• Filed: 12/19/2011
• Issued: 11/20/2012
• Est. Priority Date: 08/15/2005
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Snee, Preston T., Somers, Rebecca C., Nocera, Daniel G., Bawendi, Moungi G.
• Primary Examiner(s): Gakh, Yelena G
• Application Number:
  US13/330,148
• Publication Number:
  US 20120094390A1
• Time in Patent Office: 337 Days
• Field of Search: None
• US Class Current: 436/518
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• CPC Class Codes: G01N 33/542 with steric inhibition or signal modification, e.g. fluorescent quenching
• CPC Class Codes: Y10T 436/207497 Molecular oxygen

Abstract

Binding an analyte can cause a change in fluorescence emission of a sensor. The change in fluorescence can be related to the amount of analyte present. The sensor can include a semiconductor nanocrystal linked to a fluorescent moiety. Upon excitation, the fluorescent moiety can transfer energy to the semiconductor nanocrystal, or vice versa.

Claims

1. A composition comprising:

a fluorescent semiconductor nanocrystal including a core including a first semiconductor material and optionally including one or more overcoatings including a second semiconductor material on a surface of the core;

a ligand bound to a surface of the semiconductor nanocrystal; and

a fluorescent sensor associated with the semiconductor nanocrystal via the ligand;

wherein the semiconductor nanocrystal is capable of transferring energy to the fluorescent sensor when excited, or the fluorescent sensor is capable of transferring energy to the semiconductor nanocrystal when excited, wherein the fluorescent moiety is capable of binding an analyte.

2. The composition of claim 1, wherein the ligand includes a hydrophobic region.

3. The composition of claim 2, wherein the fluorescent sensor is linked to an amphiphilic compound including a hydrophobic region.

4. The composition of claim 3, wherein the fluorescent sensor is associated with the semiconductor nanocrystal via hydrophobic interactions between the hydrophobic region of the ligand and the hydrophobic region of the amphiphilic compound.

5. The composition of claim 4, wherein the amphiphilic compound is an amphiphilic polymer.

6. The composition of claim 5, wherein the amphiphilic polymer includes a plurality of the fluorescent sensor.

7. The composition of claim 1, wherein the fluorescent sensor is covalently bound to the ligand.

8. The composition of claim 1, wherein the fluorescent sensor is a sensor for H⁺, Li⁺, Na⁺, K⁺, Cs⁺, Ag⁺, Mg²⁺, Ca²⁺, Cu²⁺, Zn²⁺, Cd²⁺, Hg²⁺, Pb²⁺, Fe³⁺, histidine, H₂PO₄⁻

, O₂, a carbohydrate, polypeptide N-terminal lysine, L-DOPA, GTP, F⁻

, inositol triphosphate, or nicotine.

9. A method for detecting an analyte in a sample, comprising:

contacting the sample with a composition including;

a fluorescent semiconductor nanocrystal including a core including a first semiconductor material and optionally including one or more overcoatings including a second semiconductor material on a surface of the core;

a ligand bound to a surface of the semiconductor nanocrystal; and

a fluorescent sensor associated with the semiconductor nanocrystal via the ligand;

wherein the semiconductor nanocrystal is capable of transferring energy to the fluorescent sensor when excited, or the fluorescent sensor is capable of transferring energy to the semiconductor nanocrystal when excited, wherein the fluorescent moiety is capable of binding an analyte;

illuminating the sample with an excitation wavelength, thereby illuminating the composition; and

measuring a fluorescent emission of the composition.

10. The method of claim 9, wherein measuring a fluorescent emission of the composition includes measuring a fluorescence emission intensity at an emission wavelength of the semiconductor nanocrystal.

11. The method of claim 9, wherein measuring a fluorescent emission of the composition includes measuring a fluorescence emission intensity at an emission wavelength of the fluorescent sensor.

12. The method of claim 9, wherein measuring a fluorescent emission of the composition includes measuring a ratio of a fluorescence emission intensity of the semiconductor nanocrystal to a fluorescence emission intensity of the fluorescent sensor.

13. The method of claim 9, further comprising determining a concentration of the analyte based on the measured fluorescent emission.

14. The method of claim 9, wherein the analyte is H⁺, Li⁺, Na⁺, K⁺, Cs⁺, Ag⁺, Mg²⁺, Ca²⁺, Cu²⁺, Zn²⁺, Cd²⁺, Hg²⁺, Pb²⁺, Fe³⁺, histidine, H₂PO₄⁻

, O₂, a carbohydrate, polypeptide N-terminal lysine, L-DOPA, GTP, F, inositol triphosphate, or nicotine.

15. The method of claim 9, wherein the sample is a biological sample.

16. A method of making a composition, comprising:

providing a fluorescent semiconductor nanocrystal including a core including a first semiconductor material and optionally including one or more overcoatings including a second semiconductor material on a surface of the core; and

a ligand bound to a surface of the semiconductor nanocrystal;

associating a fluorescent sensor with the semiconductor nanocrystal via the ligand;

wherein, once associated, the semiconductor nanocrystal is capable of transferring energy to the fluorescent sensor when excited, or the fluorescent sensor is capable of transferring energy to the semiconductor nanocrystal when excited, wherein the fluorescent moiety is capable of binding an analyte.

17. The method of claim 16, wherein the ligand includes a hydrophobic region.

18. The method of claim 17, wherein the fluorescent sensor is linked to an amphiphilic compound including a hydrophobic region.

19. The method of claim 18, wherein the fluorescent sensor is associated with the semiconductor nanocrystal via hydrophobic interactions between the hydrophobic region of the ligand and the hydrophobic region of the amphiphilic compound.