FUNCTIONALIZATION OF AND USE OF FUNCTIONALIZED SECOND HARMONIC GENERATING NANOPROBES
First Claim
1. A method of functionalizing second harmonic generating probe nanostructure comprising:
- providing a probe nanostructure formed from a nanocrystalline material capable of exposing free surface hydroxyls, the probe nanostructure defining an outer surface and having no inversion symmetry such that it generates a second harmonic emission when radiated by an external excitation source;
hydroxylating the probe nanostructure to form an activated outer surface thereof;
attaching a plurality of modifying molecules having amine terminal groups to the hydroxylates of the activated outer surface of the probe nanostructure to form a functionalization platform on said outer surface of the probe nanostructure; and
functionalizing the amine terminal groups of the functionalization platform with a plurality of functionalization molecules to form a functionalized probe nanostructure.
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Abstract
Functionalized second harmonic nanoprobes for imaging samples and a method of using such probes to monitor the dynamics different processeses using a variety of imaging techniques are provided. The functionalized second harmonic generating (SHG) nanoprobes are comprised of various kinds of nanocrystalline materials that do not possess an inversion symmetry and therefore are capable of generating second harmonic signals that can then be detected by conventional two-photon microscopy, and are provided with functional surface modifications that allow for targeted imaging of a variety of biological and non-biological processes and structures such as cell signaling, neuroimaging, protein conformation probing, DNA conformation probing, gene transcription, virus infection and replication in cells, protein dynamics, tumor imaging and cancer therapy evaluation and diagnosis as well as quantification in optical imaging.
18 Citations
36 Claims
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1. A method of functionalizing second harmonic generating probe nanostructure comprising:
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providing a probe nanostructure formed from a nanocrystalline material capable of exposing free surface hydroxyls, the probe nanostructure defining an outer surface and having no inversion symmetry such that it generates a second harmonic emission when radiated by an external excitation source; hydroxylating the probe nanostructure to form an activated outer surface thereof; attaching a plurality of modifying molecules having amine terminal groups to the hydroxylates of the activated outer surface of the probe nanostructure to form a functionalization platform on said outer surface of the probe nanostructure; and functionalizing the amine terminal groups of the functionalization platform with a plurality of functionalization molecules to form a functionalized probe nanostructure. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15)
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16. A functionalized probe nanostructure comprising:
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a nanocrystalline body capable of exposing free surface hydroxyls defining an outer surface and having no inversion symmetry such that it generates a second harmonic signal when illuminated by an external excitation source, a functionalization platform comprising a plurality of modifying molecules having amine terminal groups, the modifying molecules being linked to the outer surface of the body through a plurality of hydroxyl molecules; and a plurality of functionalization molecules bound to the amine terminal groups of the functionalization platform. - View Dependent Claims (17, 18, 19, 20, 21, 22, 23, 24, 25, 26)
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27. A method of probing structures and biological processes comprising:
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interspersing a functionalized probe nanostructure configured with a biologically relevant functionalization molecule bound to the probe nanostructure through a functionalization platform including a plurality of modifying molecules having amine terminal groups, the modifying molecules being linked to the outer surface of the body through a plurality of hydroxyl molecules, and wherein the probe nanostructure has no inversion symmetry such that it generates a second harmonic signal when illuminated by an excitation source; the functionalization molecule being selected to target a species of interest, such that the functionalized probe nanostructure interacts with the targeted species of interest; illuminating the probe nanostructure with an external excitation source; and detecting the second harmonic signal from the nanoprobe. - View Dependent Claims (28, 29, 30, 31, 32, 33, 34, 35, 36)
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Specification