Granted Patent B2

US 9,005,985 · App. 13/761,447 · Granted Apr 14, 2015

Inventors: Thomas Kwok (Miller Place, NY); Benjamin MingHwa Liang (East Setauket, NY); Stephane Shu Kin So (South Portland, ME)

Assignee: APDN (B.V.I.) Inc.

C12Q1/6876C08K5/09C09D7/1233C09D11/03C12Q1/6816B82Y15/00Y10S977/774Y10S977/92

Abstract

Claims (107)

1. A composition of the formula I:

(cOpR)-[L-(NA)] m   I

wherein:

m is an integer greater than 1;

(cOpR) is a coated optical reporter particle, wherein the cOpR comprises an upconverting phosphor (UCP) material of the formula Na(Y x Yb y Er z )F 4 , and wherein:

x is from about 0.6 to about 0.95;

y is from about 0.05 to about 0.35; and

z is from about 0.1 to about 0.001;

(NA) is a nucleic acid oligomer of detectable sequence; and

L is a linking group covalently bound to the coated optical reporter particle and to the nucleic acid oligomer;

provided that at least one of the following applies:

x is not from 0.7 to 0.9; and/or

y is not from 0.08 to 0.29; and/or

z is not from 0.01 to 0.06.

2. The composition of claim 1 , wherein (NA) is a single stranded DNA molecule having a length of between about 40 nucleotides and about 1000 nucleotides or a double stranded DNA molecule having a length of between about 40 base pairs and about 1000 base pairs.

3. The composition of claim 1 , wherein L comprises an alkylene moiety having a first end covalently bound to the coated optical reporter particle and a second end covalently bound to the nucleic acid oligomer.

4. The composition of claim 1 , wherein L is of the formula:

-A-R 1 —B—

wherein:

R 1 is C 2-8 alkylene;

-A- is a group covalently bonded to the surface of the coated optical reporter; and

—B— is a group covalently bonded to the 3′ or 5′ end of the nucleic acid oligomer.

5. The composition of claim 4 , wherein -A- is —O—.

6. The composition of claim 4 , wherein —R 1 — is —(CH 2 ) n — and wherein n is from 2 to 8.

7. The composition of claim 4 , wherein —B— is:

—S—;

—O—;

—NR a —;

—S—(CH 2 ) p —;

—O—(CH 2 ) p —;

—NR a —(CH 2 ) p —;

—S—(CH 2 ) q —C(O)—NR a —(CH 2 ) p —;

—O—(CH 2 ) q —C(O)—NR a —(CH 2 ) p —;

—NR a —(CH 2 ) q —C(O)—NR a —(CH 2 ) p —;

—S—C(O)—(CH 2 ) r —C(O)—NR a —(CH 2 ) p —;

—O—C(O)—(CH 2 ) r —C(O)—NR a —(CH 2 ) p —; or

—NR a —C(O)—(CH 2 ) r —C(O)—NR a —(CH 2 ) p —;

wherein:

p is from 2 to 8;

q is from 1 to 8;

r is from 2 to 8; and

each R a is independently hydrogen or C 1-6 alkyl.

8. The composition of claim 4 , wherein —B— is:

—S—(CH 2 ) q —C(O)—NR a —(CH 2 ) p or

—NR a —C(O)—(CH 2 ) r —C(O)—NR a —(CH 2 ) p ;

wherein:

p is from 2 to 8;

q is from 1 to 8;

r is from 2 to 8; and

each R a is independently hydrogen or C 1-6 alkyl.

9. The composition of claim 8 , wherein:

p is from 2 to 6;

q is from 1 to 3; and

r is 2 or 3.

10. The composition of claim 4 , wherein —B— is:

—S—CH 2 —C(O)—NH—(CH 2 ) 6 —; or

—NH—C(O)—(CH 2 ) 3 —C(O)—NH—(CH 2 ) 6 —.

11. The composition of claim 1 , wherein the cOpR is coated with silica.

12. A composition of the formula II:

(UCP)-[A-R 1 —X—R 2 —C(O)—NR a —R 3 -(DNA)] m   II

wherein:

m is an integer greater than 1;

UCP is an upconverting phosphor particle of the formula Na(Y x Yb y Er z )F 4 , wherein:

x is from about 0.6 to about 0.95;

y is from about 0.05 to about 0.35; and

z is from about 0.1 to about 0.001;

DNA is a single or double stranded deoxyribonucleic acid oligomer;

-A- is a group covalently bound to a surface of the UCP;

R 1 is C 2-8 alkylene,

R 2 is C 1-8 alkylene or —C(O)—C 1-8 alkylene-;

—X— is —O—, —S— or —NR a —;

R 3 is C 2-8 alkylene; and

R a is hydrogen or C 1-6 alkyl;

provided that at least one of the following applies:

x is not from 0.7 to 0.9; and/or

y is not from 0.08 to 0.29; and/or

z is not from 0.01 to 0.06.

13. The composition of claim 12 , wherein the composition is of the formula IV:

(UCP)—[O—(CH 2 ) s —S—(CH 2 ) t —C(O)—NH—(CH 2 ) v -(DNA)] m   IV

wherein:

s is from 2 to 6;

v is from 2 to 6; and

t is from 1 to 3.

14. The composition of claim 12 , wherein the composition is of the formula V:

(UCP)—[O—(CH 2 ) s —NH—C(O)—(CH 2 ) u —C(O)—NH—(CH 2 ) v -(DNA)] m   V

wherein:

s is from 2 to 6;

v is from 2 to 6; and

u is 2 or 3.

15. The composition of claim 12 , wherein the composition is of the formula VI:

(UCP)—[O—(CH 2 ) 3 —S—CH 2 —C(O)—NH—(CH 2 ) 6 -(DNA)] m   VI.

16. The composition of claim 12 , wherein the composition is of the formula VII:

(UCP)—[O—(CH 2 ) 3 —NH—C(O)—(CH 2 ) 3 —C(O)—NH—(CH 2 ) 6 -(DNA)] m   VII.

17. The composition of claim 1 , wherein the cOpR comprises a visually detectable light emitting material selected from the group consisting of a fluorescent dye, a ceramic powder, or a quantum dot.

18. The composition of claim 17 , where said light emitting materials are excitable by a UV light source or an infrared light source.

19. The composition of claim 1 , wherein the cOpR comprises at least one electromagnetic radiation-emitting material.

20. The composition of claim 19 , where the electromagnetic radiation-emitting material is detectable by devices which provide sources selected from the group consisting of an infrared radiation source, magnetic field source, a quantum dot or electromagnetic pulse.

21. A composition of the formula I:

(cOpR)-[L-(NA)] m   I

wherein:

m is an integer greater than 1;

(cOpR) is a coated optical reporter particle, wherein the cOpR comprises an upconverting phosphor (UCP) material of the formula Na(Y x Yb y Er z )F 4 , and wherein:

x is from about 0.6 to about 0.95;

y is from about 0.05 to about 0.35; and

z is from about 0.1 to about 0.001;

(NA) is a nucleic acid oligomer; and

L is a linking group covalently bound to the coated optical reporter particle and to the nucleic acid oligomer, wherein the linking group L comprises an alkylene moiety having a first end covalently bound to the coated optical reporter particle and a second end covalently bound to the nucleic acid oligomer.

Assignments (3)

Continuity (14)