Method for detection of binding affinities

Patent metadata

Field	Value
Publication number	US-10684227-B2
Application number	US-201816007497-A
Country	US
Kind code	B2
Filing date	Jun 13, 2018
Priority date	Jan 17, 2012
Publication date	Jun 16, 2020
Grant date	Jun 16, 2020

Abstract

A method for the detection of binding affinities comprises providing a device having a planar waveguide ( 2 ) arranged on a substrate ( 3 ) and an optical coupler ( 4 ). Coherent light ( 1 ) of a predetermined wavelength is coupled into the planar waveguide ( 2 ) such that the coherent light propagates along the planar waveguide ( 2 ), with an evanescent field ( 6 ) of the coherent light propagating along an outer surface ( 5 ) of the planar waveguide ( 2 ). Target samples ( 8 ) attached to binding sites ( 7 ) are arranged along a plurality of predetermined lines ( 9 ) on the outer surface ( 5 ) of the planar waveguide ( 2 ). At a predetermined detection location, light of the evanescent field which is scattered by target samples ( 8 ) bound to binding sites ( 7 ) arranged along the predetermined lines ( 9 ) is detected. The light scattered by the target samples ( 8 ) bound to the binding sites ( 7 ) has, at the predetermined detection location, a difference in optical path length which is an integer multiple of the predetermined wavelength of the light.

First claim

The invention claimed is:

1. A method for detection of binding affinities of target samples to binding sites, the method comprising the steps of:
providing a device comprising a planar waveguide arranged on a substrate and an optical coupler,
coupling coherent light of a predetermined wavelength into the planar waveguide such that the coherent light propagates along the planar waveguide with an evanescent field of the coherent light propagating along an outer surface of the planar waveguide,
attaching the target samples to the binding sites arranged along a plurality of predetermined lines on the outer surface of the planar waveguide,
detecting, at a predetermined detection location, light of the evanescent field scattered by the target samples bound to the binding sites arranged along the predetermined lines, the light scattered by the target samples bound to the binding sites having, at the predetermined detection location, a difference in optical path length which is an integer multiple of the predetermined wavelength of the light, and from the light detected at the predetermined detection location,
determining the binding affinities of the target samples to the binding sites.

2. A method according to claim 1 , wherein the predetermined lines with the target samples attached thereto are arranged such that the coherent light scattered by the target samples bound to the binding sites interferes at the predetermined detection location with a difference in optical path length which is an integer multiple of the predetermined wavelength of the coherent light, so that a maximum of light scattered by the target samples bound to the binding sites is located at the predetermined detection location, and wherein binding of the target samples to the binding sites is determined when the said maximum of light scattered by the target samples bound to the binding sites is detected at the predetermined detection location.

3. A method according to claim 1 , wherein the distance between adjacent predetermined lines decreases in the direction of propagation of the light of the evanescent field.

4. A method according to claim 1 , wherein the plurality of predetermined lines along which the binding sites are arranged comprises curved lines, the curvature of the lines being such that light of the evanescent field scattered by the target samples bound to the binding sites interferes at a predetermined detection point as detection location.

5. A method according to according to claim 1 , wherein the plurality of predetermined lines are arranged on the outer surface of the planar waveguide in a manner such that their locations are geometrically defined by the equation

x
j

=

λ
⁢

⁢

N
⁡

(

A
0

+
j

)

-

n
s
2

⁡

(

N
2

-

n
s
2

)

⁢

(

y
j
2

+

f
2

)

+

(

n
s

⁢
λ

)

2

⁢

(

A
0

+
j

)

2

N
2

-

n
s
2

wherein:
λ is the vacuum wavelength of the propagating light,
N is the effective refractive index of the guided mode in the planar waveguide; N depends on the thickness and the refractive index of the planar waveguide, the refractive index of the substrate, the refractive index of a medium on the outer surface of the planar waveguide and the polarization of the guided mode,
n s is the refractive index of the substrate,
f is the thickness of the substrate,
A 0 is an integer which is chosen to be close to the product of the refractive index n s and the thickness f of the substrate divided by the wavelength λ, and
j is a running integer that indicates the index of the respective line.

6. A method according to claim 1 , wherein the binding sites comprise capture molecules attached to the surface of the planar waveguide along the predetermined lines only, the capture molecules being capable of binding the target samples.

7. A method according to claim 1 , wherein the binding sites comprise capture molecules capable of binding the target samples, the capture molecules capable of binding the target samples being arranged along the predetermined lines by dispensing capture molecules capable of binding the target samples onto the outer surface of the planar waveguide and by deactivating those capture molecules which are not arranged along the predetermined lines.

8. A method according to claim 1 , wherein the planar waveguide has a refractive index (n w ) which is substantially higher than the refractive index (n

Assignees

• Hoffmann La Roche

Inventors

• Fattinger Christof

Classifications

• G01N21/552 Primary

  Attenuated total reflection · CPC title

• G01N21/7743

  the reagent-coated grating coupling light in or out of the waveguide · CPC title

• G01N33/54373

  involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings · CPC title

• G01N21/75 Primary

  Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated (systems in which material is burnt in a flame or plasma G01N21/72, G01N21/73) · CPC title