Evanescent wave sensor with attached ligand

• US 20060269930A1
• Filed: 05/31/2005
• Published: 11/30/2006
• Est. Priority Date: 05/31/2005
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Roitman, Daniel B., Robotti, Karla M.
• Granted Patent: US 7,396,676 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: G01N 21/553 and using surface plasmons fluorescence excitation G01N21/648; enhanced Raman G01N21/658
• CPC Class Codes: G01N 33/54353 with ligand attached to the carrier via a chemical coupling agent coatings G01N33/54393
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10S 436/805 Optical property

Abstract

The invention in particular embodiments provides an evanescent wave sensor which includes a ligand bound to a sensor substrate via a NCYX linker moiety, as defined herein. Methods of making the subject evanescent wave sensors are also provided which include contacting a first reactive moiety which has an isocyanato (or isothiocyanato) moiety with a second reactive moiety which has an hydroxyl, thiol, or amino moiety, as further described herein. Also provided by the invention are methods in which a subject evanescent wave sensor is contacted with a sample, and binding of analytes in the sample to the sensor is assessed by evanescent wave detection. The invention also provides kits and systems for performing the subject methods.

Claims

1. A method of making an evanescent wave sensor, the method comprising

contacting a first reactive moiety having the structure

R1-N═

C═

Y1

with a second reactive moiety having the structure

R2-X1H_m

under conditions sufficient to result in a compound having the structure

wherein;

one of R1 or R2 is a sensor substrate;

the other of R1 or R2 is selected from a ligand, a linking group bound to a ligand, a functional group for binding a ligand, or a linking group bound to a functional group for binding a ligand;

Y1 is selected from O or S;

X1 is selected from N or S, provided that, if Y1 is S, X1 is N;

n equals 1 when X1 is N, or n equals 0 when X1 is S; and

m equals n plus 1.

2. A method according to claim 1, wherein the ligand is selected from an antibody, an antigen, a protein, a polynucleotide, a cell, a cell fragment, a bacterium, a spore, a virus, or a virion.

3. A method according to claim 1, wherein the sensor substrate comprises a light transmissive support.

4. A method according to claim 3, wherein the sensor substrate comprises a metal layer bound to the light transmissive support.

5. A method according to claim 4, wherein the metal layer comprises a metal selected from copper, silver, aluminum, gold, platinum, palladium, chromium, niobium, rhodium, or iridium.

6. A method according to claim 4, wherein the sensor substrate comprises a glass layer bound to the metal layer.

7. A method according to claim 3, wherein the sensor substrate comprises a metal oxide layer bound to the light transmissive support.

8. A method according to claim 3, wherein the sensor substrate comprises a self assembled monolayer bound to the light transmissive support.

9. A method according to claim 3, wherein the sensor substrate comprises a polymer layer bound to the light transmissive support.

10. A method according to claim 3, wherein the sensor substrate further comprises a linking group via which the light transmissive support is bound to either the —

N═

C═

Y1 or the —

X1H_m.

11. A method according to claim 3, wherein the light transmissive support comprises one or more materials selected from glass, quartz, silica, a polymeric material, an acrylic polymer, a cyclic olefin, a polyolefin, a polydimethylsiloxane, a polymethylmethyl acrylate, and a polycarbonate.

12. A method according to claim 1, wherein R1 is the sensor substrate, the sensor substrate comprises a light transmissive support bound to a linking group, and the —

N═

C═

Y1 group is bound to the light transmissive support via the linking group.

13. An evanescent wave sensor having the structure:

14. An evanescent wave sensor according to claim 13, wherein the ligand is selected from an antibody, an antigen, a protein, a polynucleotide, a cell, a cell fragment, a bacterium, a spore, a virus, a virion, a drug compound, an organic compound.

15. An evanescent wave sensor according to claim 13, wherein the evanescent wave sensor comprises a plurality of different ligands bound to the sensor substrate, each of the plurality of different ligands bound to the sensor substrate at a different site.

16. An evanescent wave sensor according to claim 13, wherein the evanescent wave sensor comprises an array having a plurality of features, each of the plurality of features having a respective ligand bound to the sensor substrate, each of the plurality of features being addressably located at a respective site on the sensor substrate.

17. An evanescent wave sensor according to claim 13, wherein the sensor substrate comprises a light transmissive support.

18. An evanescent wave sensor according to claim 17, wherein the sensor substrate further comprises a metal layer bound to the light transmissive support.

19. An evanescent wave sensor according to claim 18, wherein the metal layer comprises a metal selected from copper, silver, aluminum, gold, platinum, palladium, chromium, niobium, rhodium, or iridium.

20. An evanescent wave sensor according to claim 18, wherein the sensor substrate comprises a glass layer bound to the metal layer.

21. An evanescent wave sensor according to claim 17, wherein the sensor substrate comprises a metal oxide layer bound to the light transmissive support.

22. An evanescent wave sensor according to claim 17, wherein the sensor substrate comprises a self assembled monolayer bound to the light transmissive support.

23. An evanescent wave sensor according to claim 17, wherein the sensor substrate comprises a polymer layer bound to the light transmissive support.

24. An evanescent wave sensor according to claim 17, wherein the sensor substrate further comprises a linking group via which the light transmissive support is bound to the ligand.