Device for use in the detection of binding affinities

Patent metadata

Field	Value
Publication number	US-10060917-B2
Application number	US-201414904039-A
Country	US
Kind code	B2
Filing date	Jul 11, 2014
Priority date	Jul 12, 2013
Publication date	Aug 28, 2018
Grant date	Aug 28, 2018

Abstract

A device ( 1 ) for use in the detection of binding affinities comprises a planar waveguide ( 2 ) arranged on a substrate ( 22 ). The waveguide ( 2 ) has an outer surface ( 21 ) and a plurality of incoupling lines ( 31 ) for coupling a beam of coherent light into the waveguide ( 2 ) such that a parallel beam of coherent light ( 62 ) propagates along the waveguide ( 2 ). The incoupling lines ( 31 ) are curved and have an increasing distance between adjacent incoupling lines ( 31 ). A divergent beam of coherent light ( 61 ) of a predetermined wavelength is coupled into the waveguide ( 2 ) such that it propagates along the waveguide ( 2 ). A plurality of binding sites ( 51 ) is attached to the outer surface ( 21 ) along at least one further plurality of diffraction lines arranged in an outcoupling section of the waveguide ( 2 ). These diffraction lines comprise a plurality of curved outcoupling lines ( 41 ) having a decreasing distance between adjacent outcoupling lines. They decouple a diffracted portion of coherent light from the planar waveguide ( 2 ), and the decoupled portion of coherent light ( 63 ) converges into a predetermined second focal location ( 631 ).

First claim

The invention claimed is:

1. A device for use in the detection of binding affinities, the device comprising a planar waveguide arranged on a substrate, the planar waveguide having an outer surface and a plurality of incoupling lines for coupling a beam of coherent light into the planar waveguide in a manner such that in operation a parallel beam of coherent light propagates along the planar waveguide with an evanescent field propagating along the outer surface thereof, wherein the plurality of incoupling lines are arranged at a first surface portion of the outer surface or the planner waveguide and are curved and arranged to have an increasing distance between adjacent incoupling lines when viewed in the direction of propagation of the parallel beam of coherent light along the planar waveguide, the arrangement of the plurality of incoupling lines and the distance between adjacent incoupling lines being such that in operation a divergent beam of coherent light of a predetermined wavelength coming from a predetermined first focal location and impinging on the plurality of incoupling lines is coupled into the planar waveguide in a manner such that the parallel beam of coherent light propagates along the planar waveguide, wherein a plurality of binding sites capable of binding a target sample is attached to the outer surface along at least one further plurality of lines arranged in an outcoupling section of the planar waveguide, the at least one further plurality of lines comprising a plurality of curved outcoupling lines which are arranged at a second portion of the outer surface of the planar waveguide and are arranged to have a decreasing distance between adjacent curved outcoupling lines when viewed in the direction of propagation of the coherent light impinging thereon so as to be capable of diffracting a portion of the coherent light of the predetermined wavelength impinging on the curved outcoupling lines to decouple it from the planar waveguide in a manner such that the decoupled portion of coherent light of the predetermined wavelength converges into a predetermined second focal location to provide at the second focal location a signal which, when compared to a known signal representative of the binding sites only, is representative of the binding affinity between the binding sites and the target sample, wherein the first surface portion includes a blank section in which there are no lines and wherein the second surface portion includes a further blank section in which there are no lines, the blank sections being formed to avoid a second order Bragg reflection.

2. The device according to claim 1 , wherein the first surface portion and the second surface portion are arranged spatially separated at the outer surface of the planar waveguide.

3. The device according to claim 1 , wherein the first surface portion and the second surface portion are arranged at the outer surface of the planar waveguide to at least partially overlap in a manner such that the blank section and the further blank section form a common blank section.

4. The device according to claim 1 , wherein first surface portion and the second surface portion are of the same size.

5. The device according to claim 1 , wherein the at least one further plurality of lines arranged in the outcoupling section further comprises a plurality of straight lines, the straight lines running parallel to one another with a constant distance between adjacent straight lines and being arranged at an angle (β) relative to the direction of propagation of the parallel beam of coherent light in a manner such that a portion of the parallel beam of coherent light is diffracted under a diffraction angle (α) relative to the straight lines such that the diffracted portion of the parallel beam of coherent light impinges onto the plurality of curved outcoupling lines, and wherein the attached binding sites are arranged along the plurality of straight lines or along the plurality of curved outcoupling lines.

6. The device according to claim 5 , wherein the plurality of curved outcoupling lines is arranged at the outer surface in a partition of the planar waveguide through which the portion of the parallel beam of coherent light diffracted at the straight lines propagates, and through which no other light of the parallel beam of coherent light propagates.

7. The device according to claim 1 , wherein a surface coating layer is arranged on top of the outer surface of the planar waveguide, the surface coating layer having a porous internal structure to allow target sample applied to the coating layer to diffuse therethrough to reach the binding sites attached to the outer surface of the planar waveguide.

8. A method for the detection of binding affinities, the method comprising the steps of:
providing a device according to any one of the preceding claims,
applying to the outcoupling section of the planar waveguide along the at least one further plurality of lines where the binding sites are arranged a target sample for which the binding affinity between the binding sites and the target sample is to be detected,
generating at the predetermined first focal location a divergent beam of coherent light in a manner so as to impinge on the plurality of incoupling lines of the planar waveguide to couple the divergent beam of coherent light into the planar waveguide in a manner such that the beam of coherent light coupled into the planar waveguide propagates as a parallel beam of coherent light along the planar waveguide with an evanescent field of the parallel beam of coherent light propagating along the outer surface thereof, wherein a portion of the coherent light is diffracted by the plurality of curved outcoupling lines of the outcoupling section of the planar waveguide to decouple it from the planar waveguide in a manner such that the decoupled portion of the coherent light converges into the second predetermined focal location, and
detecting the decoupled portion of coherent light at the second predetermined focal location to form a signal and comparing this formed signal with a known signal representative of the binding sites only to provide a signal representative of the binding affinity between the binding sites and the target sample.

9. The method according to claim 8 , wherein the decoupled portion of coherent light is detected in a detection zone having a predetermined size and being arranged to include the second predetermined focal location to determine that location in the detection zone, where the decoupled portion of coherent light of the predetermined wavelength has a relative maximum intensity, and defining the location of the relative maximum intensity as the second predetermined focal location.

10. The method according to claim 9 , wherein the divergent beam of coherent light is successively generated at different locations in a beam generation zone having a predetermined size and being arranged to include the first predetermined focal location, wherein for each successively generated beam of coherent light that location in the detection zone having the relative maximum intensity of the decoupled portion of coherent light is determined, defining that location in the detection zone where the relative maximum intensity is highest as the second predetermined focal location, and defining that location in the beam generation zone where the corresponding beam is generated as the first predetermined focal location.

11. The method according to claim 10 , wherein the beam generation zone is an area in a first plane parallel to the outer surface of the planar waveguide, and wherein the detection zone is a straight line extending parallel to the direction of propagation of the parallel b

Assignees

• Hoffmann La Roche
• Hoffmann La Roche

Inventors

• Fattinger Christof

Classifications

• G01N33/54386 Primary

  Analytical elements · CPC title

• G01N21/7743 Primary

  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