Granted Patent B2

US 12,544,462 · App. 17/765,310 · Granted Feb 10, 2026

Inventors: Yoke Khin Yap (Houghton, MI); Dongyan Zhang (Houghton, MI); Nazmiye Yapici (South Lyon, MI); Xiuling Liu (Ann Arbor, MI)

A61K49/0054G01N33/533G01N33/54353B82Y30/00

Abstract

Claims (33)

1 . A compound, comprising:

a boron nitride carrier;

a first linker having a first end connected to the carrier;

a second linker having a first end connected to the carrier;

a third linker having a first end connected to the carrier;

a fourth linker having a first end connected to the carrier;

a first fluorescent entity connected to a second end of the first linker;

a second fluorescent entity different from the first fluorescent entity connected to a second end of the second linker;

a third fluorescent entity different from the first and second fluorescent entities connected to a second end of the third linker, wherein a ratio of fluorescence intensities is x:y:z for the first, second, and third fluorescent entities, respectively, and further wherein at least two of x, y, and z is 1; and

a biomolecule connected to a second end of the fourth linker, wherein the biomolecule is configured to connect to biomarker.

2 . The compound of claim 1 , wherein the carrier is a boron nitride nanotube (BNNT).

3 . The compound of claim 1 , wherein the carrier is a nanodot.

4 . The compound of claim 1 , wherein the first end of at least one of the first, second, third, and fourth linkers is covalently bonded to the carrier.

5 . The compound of claim 4 , wherein the first end of at least one of the first, second, third, and fourth linkers includes a functional group, and the functional group covalently bonds the linker to the carrier.

6 . The compound of claim 4 , wherein the second end of at least one of the first, second, third, and fourth linkers is covalently bonded to one of the first and second fluorescent entities or the biomolecule via a functional group.

7 . The compound of claim 1 , wherein the first end of at least one of the first, second, third, and fourth linkers is non-covalently bonded to the carrier.

8 . The compound of claim 7 , wherein at least one of the first, second, third, and fourth linkers is amphiphilic, and includes a hydrophobic region and a hydrophilic region, and wherein the hydrophobic region is non-covalently bonded to the carrier.

9 . The compound of claim 7 , wherein at least one of the first, second, third and fourth linkers has a molecular weight between about 1000 and 10000 Da.

10 . The compound of claim 1 , wherein at least one of the at least one of the first, second, third, and fourth linkers is DSPE-PEG n (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[(polyethylene glycol) n ]), where n is a number of polyethylene glycol (PEG) molecules in a PEG chain.

11 . A method of detecting biomarkers, comprising:

providing a plurality of fluorophores to a sample, each of the plurality of fluorophores including a biomolecule, a first fluorescent entity, a second fluorescent entity, and a third fluorescent entity linked to a carrier, wherein the biomolecule is configured to interact with a plurality of biomarkers in the sample, and whereby the fluorophore connects to the biomolecule;

exciting the plurality of fluorophores in the sample with a laser; and

detecting at least one of an identity and a quantity of the plurality of biomarkers in the sample based on a fluorescence spectra emitted by the excited plurality of fluorophores;

wherein a ratio of fluorescence intensities is x:y:z for the first, second, and third fluorescent entities, respectively, and further wherein at least two of x, y, and z is 1.

12 . The method of claim 11 , wherein the carrier is a boron nitride nanotube (BNNT) carrier, or a nanodot.

13 . The method of claim 11 , wherein the first and second fluorescent entities and the biomolecule are linked to the carrier by first, second, third, and fourth linkers, and wherein at least one of the first, second, third, and fourth linkers is linked to the carrier via a covalent bond.

14 . The method of claim 11 , wherein the first, second, and third fluorescent entities and the biomolecule are linked to the carrier by first, second, third, and fourth linkers, respectively, and wherein at least one of the first, second, third, and fourth linkers is linked to the carrier via a non-covalent bond.

15 . The method of claim 14 , wherein at least one of the first, second, third, and fourth linkers is amphiphilic, and includes a hydrophobic region and a hydrophilic region, and wherein the hydrophobic region is non-covalently bonded to the carrier.

16 . The method of claim 15 , wherein at least one of the first, second, third and fourth linkers has a molecular weight between about 1000 and 10000 Da.

17 . The method of claim 11 , wherein the plurality of fluorophores is a first plurality of fluorophores, the biomarker is a first biomarker, and the biomolecule is a second biomolecule, and further comprising providing a second plurality of fluorophores to a sample, each of the second plurality of fluorophores including a second biomolecule, a fourth fluorescent entity, and a fifth fluorescent entity linked to a carrier, wherein the second biomolecule is configured to interact with a second plurality of biomarkers in the sample, and whereby the second fluorophore connects to the second biomolecule.

18 . The method of claim 17 , wherein the second plurality of fluorophores are excited by the laser, and further comprising detecting at least one of an identity and a quantity of the second plurality of biomarkers in the sample based on a fluorescence spectra emitted by the excited second plurality of fluorophores.

19 . The compound of claim 1 , wherein each of x, y, and z are 1.

20 . The compound of claim 1 , wherein two of x, y, and z are 1, and the remaining one of x, y, and z is 1.5.

Assignments (2)

Continuity (8)

References Cited (11)