Nanoprobes for detection or modification of molecules
First Claim
1. A method of detecting a target biomolecule, comprising:
- contacting a sample with a probe for a target biomolecule, wherein the probe is attached to a solid substrate, and wherein the probe comprises;
a molecular linker comprising a tether and a molecular rod, wherein the length of the rod is shorter than the persistence length of the rod material and the length of the tether is greater than the persistence length of the tether material;
a first functional group comprising an acceptor fluorophore at one end of the molecular linker; and
a second functional group comprising a donor fluorophore at the other end of the molecular linker, wherein the first and second functional groups are linked and spaced by the molecular linker, wherein the functional groups are capable of interacting with one another or with the target biomolecule in a predetermined reaction, wherein the molecular linker links the first and second functional groups sufficiently spaced from one another such that the functional groups do not substantially interact in an absence of the target biomolecule but interact in a presence of the target biomolecule to provide a signal of the presence of the biomolecule,allowing the functional groups to specifically interact with the target biomolecule;
applying laser light that can excite the donor fluorophore to enter the solid substrate;
trapping the laser light in the solid substrate by total internal reflection;
exciting the donor fluorophore, wherein when interaction of the functional groups in the presence of the target brings the acceptor fluorophore into a proximity with a donor fluorophore to permit excitation of the acceptor fluorophore by the donor fluorophore and results in the production of a signal by the acceptor fluorophore; and
detecting the signal from the acceptor fluorophore when the probe interacts with target biomolecule.
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Abstract
The disclosure provides probes for one or more target molecules. In particular examples, the probes include a molecular linker and first and second functional groups linked and spaced by the molecular linker, wherein the functional groups are capable of interacting with one another or with the target biomolecule in a predetermined reaction, and wherein the molecular linker maintains the first and second functional groups sufficiently spaced from one another such that the functional groups do not substantially interact in an absence of the target biomolecule. In the presence of the target biomolecule the functional groups interact (with each other, with the target biomolecule, or both), and in some examples a detectable signal is produced. In some examples, the functional groups can detect or modify a target molecule. Also provided are methods of using the probes, for example to detect or modify a target molecule.
71 Citations
13 Claims
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1. A method of detecting a target biomolecule, comprising:
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contacting a sample with a probe for a target biomolecule, wherein the probe is attached to a solid substrate, and wherein the probe comprises; a molecular linker comprising a tether and a molecular rod, wherein the length of the rod is shorter than the persistence length of the rod material and the length of the tether is greater than the persistence length of the tether material; a first functional group comprising an acceptor fluorophore at one end of the molecular linker; and a second functional group comprising a donor fluorophore at the other end of the molecular linker, wherein the first and second functional groups are linked and spaced by the molecular linker, wherein the functional groups are capable of interacting with one another or with the target biomolecule in a predetermined reaction, wherein the molecular linker links the first and second functional groups sufficiently spaced from one another such that the functional groups do not substantially interact in an absence of the target biomolecule but interact in a presence of the target biomolecule to provide a signal of the presence of the biomolecule, allowing the functional groups to specifically interact with the target biomolecule; applying laser light that can excite the donor fluorophore to enter the solid substrate; trapping the laser light in the solid substrate by total internal reflection; exciting the donor fluorophore, wherein when interaction of the functional groups in the presence of the target brings the acceptor fluorophore into a proximity with a donor fluorophore to permit excitation of the acceptor fluorophore by the donor fluorophore and results in the production of a signal by the acceptor fluorophore; and detecting the signal from the acceptor fluorophore when the probe interacts with target biomolecule. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
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Specification