Device for use in the detection of binding affinities

• US 10,156,524 B2
• Filed: 12/03/2013
• Issued: 12/18/2018
• Est. Priority Date: 12/04/2012
• Status: Active Grant

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Fattinger, Christof
• Primary Examiner(s): Turk, Neil N
• Application Number:
  US14/646,354
• Publication Number:
  US 20150276612A1
• Time in Patent Office: 1,841 Days
• Field of Search: None
• CPC Class Codes: G01N 2021/752 Devices comprising reaction zones
• CPC Class Codes: G01N 2021/7776 Index
• CPC Class Codes: G01N 2021/7793 Sensor comprising plural indicators
• CPC Class Codes: G01N 21/552 Attenuated total reflection
• CPC Class Codes: G01N 21/75 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 Class Codes: G01N 21/7703 using reagent-clad optical fibres or optical waveguides using measurement of total internal reflection or attenuated total reflection G01N21/552; optical fibres or waveguides per se G02B
• CPC Class Codes: G01N 21/774 the reagent being on a grating or periodic structure
• CPC Class Codes: G01N 2201/0438 Linear motion, sequential
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

A device for use in the detection of binding affinities, the device comprising a planar waveguide (2) arranged on a substrate (3), and further comprising an optical coupler (41) having a predetermined length for coupling coherent light (1) of a predetermined wavelength into the planar waveguide (2) such that a parallel beam of coherent light propagates through the planar waveguide (2) with an evanescent field (11) of the coherent light propagating along an outer surface (21) of the planar waveguide (2). The outer surface (21) of the planar waveguide (2) comprises binding sites thereon capable of binding target samples to the binding sites such that light of the evanescent field (11) is diffracted by target samples bound to the binding sites. The binding sites are arranged along a plurality of predetermined straight lines (7) running parallel to one another with a constant distance between adjacent straight lines.

Claims

1. A device for use in the detection of binding affinities, the device comprising:

a substrate having a bottom surface, a top surface, two side surfaces and two end surfaces,

a planar waveguide arranged on and in physical contact with the top surface of the substrate and having an inner surface in physical contact with the top surface of the substrate and an outer surface opposite the inner surface, the planar waveguide having a length dimension and a width dimension,

an optical coupler in physical contact with the planar waveguide and having a first plurality of grating lines, the optical coupler having a width dimension in a direction of the width dimension of the planar waveguide, the optical coupler having a length dimension in a direction of the length dimension of the planar waveguide,

a binding area positioned on the outer surface of the planar waveguide and in front of the optical coupler along the length dimension of the planar waveguide,

the binding area comprising a plurality of binding sites arranged in straight lines at a first angle to the length dimension of the planar waveguide, the plurality of binding sites arranged in straight lines comprising capture molecules, and

the binding area having a width dimension in the direction of a width dimension of the planar waveguide, the width dimension of the binding area being less than the width dimension of the optical coupler,

and

a further optical coupler in physical contact with the planar waveguide and spaced from the optical coupler and the binding area comprising the plurality of binding sites in the direction of the width dimension of the planar waveguide, the further optical coupler having a second plurality of grating lines at a second angle to the first angle along which the plurality of binding sites are arranged, the second plurality of grating lines having a respective curvature and being arranged with a decreasing distance between adjacent grating lines,

the further optical coupler being arranged outside of the width dimension of the optical coupler but within the width dimension of the planar waveguide,

wherein;

the optical coupler is configured to receive from a source a first coherent light beam of a predetermined wavelength and couple a second coherent light beam through the planar waveguide to the binding area comprising the plurality of binding sites, the capture molecules being capable of binding the target samples, the target samples configured to diffract the second coherent light beam and couple a third coherent light beam into the further optical coupler,

and

the further optical coupler being configured to couple a fourth coherent light beam out of the planar waveguide to interfere at a predetermined detection location with a difference in optical path length that is an integer multiple of the predetermined wavelength of the first coherent light beam.

2. The device according to claim 1, wherein the binding area comprising the plurality of binding sites arranged in straight lines is arranged in an effective zone on the planar waveguide, the effective zone having a width dimension equivalent to a predetermined length of the optical coupler so that the effective zone is illuminated by an evanescent field of the second coherent light beam.

3. The device according to claim 1, wherein at least two pluralities of the plurality of binding sites arranged in straight lines are arranged on the planar waveguide one after the other in the direction of the length dimension of the planar waveguide, with the further optical coupler being arranged relative to each plurality of binding sites arranged in straight lines such that the second coherent light beam that is diffracted by target samples bound to binding sites of the plurality of binding sites impinges under a diffraction angle (α

) onto the further optical coupler.

4. The device according to claim 3, wherein the at least two pluralities of the plurality of binding sites arranged in straight lines each have the same constant distance d between adjacent straight lines of the plurality of binding sites arranged in straight lines.

5. The device according to claim 3, wherein the at least two pluralities of the plurality of binding sites arranged in straight lines each have a different constant distance d1 . . . n between adjacent straight lines of the plurality of binding sites arranged in straight lines.

6. The device according to claim 5, wherein the constant distance d1 . . . n between adjacent straight lines of the plurality of binding sites arranged in straight lines differs in equal steps in the range of 0.5 nanometers to 10 nanometers.

7. The device according to claim 3, wherein the at least two pluralities of the plurality of binding sites arranged in straight lines include groups of binding sites arranged in pluralities of predetermined straight lines, each group having an equal constant distance d between adjacent straight lines of the group, and different groups of pluralities of predetermined straight lines having a different constant distance d1 . . . n between adjacent straight lines of each group.

8. The device according to claim 1, wherein the optical coupler comprises at least two portions for coupling the first coherent light beam into the planar waveguide, each of the at least two portions having a predetermined length and being laterally spaced by a predetermined distance from an adjacent portion of the at least two portions of the optical coupler such that the second coherent light beam propagates through the planar waveguide separated by the predetermined distance.

9. A system comprising a device according to claim 1 and a light source for emitting coherent light of a predetermined wavelength, the light source and the device being arranged relative to one another such that the coherent light emitted by the light source is coupled into the planar waveguide via the optical coupler.

10. The system according to claim 9, wherein:

the light source and the device are arranged relative to each other such that the coherent light emitted from the light source impinges on the optical coupler under an incoupling angle under which the coherent light emitted by the light source is coupled via the optical coupler into the planar waveguide;

the light source and the device are adjustable relative to each other for changing the incoupling angle under which the coherent light emitted by the light source is coupled via the optical coupler into the planar waveguide, and

the light source is tunable to emit light of a predetermined wavelength in a predetermined range.

11. The device according to claim 1, wherein a distance between adjacent grating lines of the first plurality of grating lines is between 100 nanometers and 1000 nanometers.