DIFFRACTIVE DEVICE FOR CHEMICAL AND BIOLOGICAL ANALYSIS

Abstract

The invention relates to a diffractive device (18) for chemical and biological analysis based on structured receptors on waveguides, which comprises: a waveguide (1) and a recognition element (3) consisting of a grating with receptors (11) arranged on the waveguide (1) and are intended to interact with target compounds (12) present in a sample; and a radiation source (4) that emits an incident beam (5) propagated through the waveguide (1), interacting with the recognition element (3) and being diffracted according to Bragg's law, thereby generating a reflected beam (6) and a transmitted beam (7), which are collected by optical analysers (8, 17) that record parameters of the reflected beam (6) and of the transmitted beam (7), enabling multiple analyses to be conducted in a simple, fast, sensitive and quantitative manner, label-free and in real time.

Claims

1. A diffractive device (18) for chemical and biological analysis intended to analyse a sample comprising target compounds (12), characterised in that it comprises: a waveguide (1) with an inlet (19) at one end, an outlet (20) at the opposite end and a test area (2) on which there is positioned a recognition element (3) comprising a grating with receptors (11) distributed across the test area (2) forming areas with receptors (13) alternating with gaps (14) without receptors, the areas with receptors (13) and gaps (14) being structured periodically according to a diffraction grating that meets Bragg's law, and the recognition element (3) being intended to interact with the target compounds (12), a radiation source (4) that emits an incident beam (5) towards the inlet (19) of the waveguide (1) that is propagated through same and diffracted by the recognition element (3), meeting Bragg's law, thereby generating a reflected beam (6) exiting through the inlet (19) and a transmitted beam (7) exiting through the outlet (20), at least one optical analyser (8, 17) that records optical parameters of the reflected beam (6) and/or of the transmitted beam (7).

2. The device (18) according to claim 1, further comprising a first optical device (9) situated between the radiation source (4) and the inlet (19) of the waveguide (1) intended to modify the radiation beams (5, 6, 7).

3. The device (18) according to claim 1, further comprising a second optical device (16) positioned at the outlet (20) of the waveguide (1) intended to modify the radiation beams (5, 6, 7).

4. The device (18) according to claim 1, wherein the radiation source (4) is a device selected from a laser, a LED diode, an incandescent lamp and a halogen lamp.

5. The device (18) according to claim 2, wherein the first optical device (9) is a device selected from a polarisation controller, a polariser, an attenuator, a monochromator, a circulator, a coupler, a Bragg grating and a long-period grating.

6. The device (18) according to claim 3, wherein the second optical device (16) is a device selected from a polarisation controller, a polariser, an attenuator, a monochromator, a circulator, a coupler, a Bragg grating and a long-period grating.

7. The device (18) according to claim 1, wherein the waveguide (1) is a waveguide selected from an optical fibre, a tapered optical fibre, a D-shaped optical fibre and an integrated optical guide.

8. The device (18) according to claim 1, wherein the waveguide (1) is made of a material selected from glass, doped glass, silicon, doped silicon, polymers, polymethylmethacrylate and polystyrene.

9. The device (18) according to claim 1, further comprising coatings (10) positioned on the waveguide (1) conferring mechanical and optical properties to the waveguide (1).

10. The device (18) according to claim 1, wherein the grating with receptors (11) is a set of elements selected from antibodies, enzymes, proteins, nucleic acids, molecularly imprinted polymers, polysaccharides, hapten-protein complexes, bacteria, viruses and tissues.

11. The device according to claim 1, wherein the recognition element (3) further comprises blocking agents (15) which are positioned in the gaps (14) without receptors.

12. The device (18) according to claim 1, wherein the first optical analyser (8) and the second optical analyser (17) are selected from a spectrophotometer, an optical spectrum analyser, a photodiode and a CMOS camera.

Description

DESCRIPTION OF THE DRAWINGS

[0045] To complement the description that is being made and for the purpose of helping to better understand the features of the invention according to a preferred practical exemplary embodiment thereof, a set of drawings is attached as an integral part of said description in which the following is depicted in an illustrative and non-limiting manner:

[0046] FIG. 1 shows a general diagram of a first embodiment of the diffractive device for chemical and biological analysis.

[0047] FIG. 2 shows a detailed diagram of the grating with receptors of the recognition element.

[0048] FIG. 3 shows a detailed diagram of the recognition element when it further comprises the blocking agents.

[0049] FIG. 4 shows a general diagram of a second embodiment of the diffractive device for chemical and biological analysis.

PREFERRED EMBODIMENT OF THE INVENTION

[0050] Below, an exemplary embodiment of the diffractive device for chemical and biological analysis is described with the aid of FIGS. 1 to 4.

[0051] The device (18) object of the present invention, which is shown in FIG. 1 in a first embodiment, comprises a waveguide (1) which is a planar waveguide (1) integrated in a substrate, and comprising an inlet (19) at one end, an outlet (20) at the opposite end and a test area (2). A recognition element (3) is positioned on the test area (2).

[0052] In a second embodiment of the invention, shown in FIG. 4, the waveguide (1) is a cylindrical fibre and the recognition element (3) is positioned surrounding same in the part comprising the test area (2), with the waveguide (1) and the recognition element (3) being concentric.

[0053] Namely, in this second embodiment, the waveguide (1) is a single-mode optical fibre 125 micrometres in diameter. The test area (2) is generated by means of the tapering of the waveguide (1) to a diameter of between 1 and 5 micrometres. The tapering is done mechanically by combining drawing and heating with a flame.

[0054] In turn, the recognition element (3) comprises a grating with receptors (11) that is arranged on the test area (2) of the waveguide (1). The grating with receptors (11) is manufactured by means of microcontact printing and covalently immobilised.

[0055] The grating with receptors (11) is distributed over the test area (2) forming areas with immobilised receptors (13) alternating with gaps (14) without receptors. This structure of areas with receptors (13) and gaps (14) is distributed periodically over the test area (2). The receptors (11) forming the areas with receptors (13) are proteins.

[0056] The recognition element (3) also comprises blocking agents (15) which are positioned in the gaps (14) without receptors. The blocking agents (15) are polysorbate molecules.

[0057] The areas with receptors (13) and gaps (14) have the same dimensions, extend in a rectilinear manner in the direction transverse to the test area (2) with a periodicity of around 550 nanometres.

[0058] Furthermore, the device (18) comprises a radiation source (4) connected to the inlet (19) of the waveguide (1) that emits an incident beam (5) towards the inlet (19), and said beam is propagated through the waveguide (1).

[0059] The radiation source (4) is a 1.3 mW SuperLed lamp with a maximum emission of 1550 nm, which is connected to the waveguide (1).

[0060] The incident beam (5) interacts with the recognition element (3) thereby generating a reflected beam (6) and a transmitted beam (7). The reflected beam (6) exits through the inlet (19) of the waveguide (1) and the transmitted beam (7) through the outlet (20) of the waveguide (1).

[0061] To perform analysis of a liquid sample containing antibodies constituting target compounds (12), said sample is incubated on the test area (2), and its concentration is quantified after incubation through the information collected from the reflected beam (6) or the transmitted beam (7). Namely, the maximum peak intensity of the reflected beam (6) and the minimum trough intensity of the transmitted beam (7) are determined.

[0062] The device (18) further comprises a first optical device (9) situated between the radiation source (4) and the inlet (19) of the waveguide (1) and a second optical device (16) positioned close to the outlet (20) of the waveguide (1). Both optical devices (9, 16) comprise a polariser, a polarisation controller and a circulator.

[0063] The device (18) also comprises a first optical analyser (8) and a second optical analyser (17), capable of recording the parameters of the electromagnetic radiation beams.

[0064] The first analyser (8) is positioned between the radiation source (4) and the inlet (19) of the waveguide (1) and is intended to record the optical parameters of the reflected beam (6). The second analyser (17) is positioned close to the outlet (20) of the waveguide (1) and is intended to record the optical parameters of the transmitted beam (7).

[0065] The optical analysers (8, 17) are optical spectrum analysers for the infrared range, connected to the waveguide (1) through the optical devices (9, 16).

[0066] In a third embodiment of the invention, a portion of the test area (2) is laterally removed to generate a flat surface (D-shaped fibres), and even part of the waveguide (1) can be removed. Test areas (2) of this type can be obtained by means of mechanical polishing or by means of chemical solution.

[0067] Furthermore, the waveguide (1) and/or the optical devices (9, 16) comprise additional elements such as Bragg gratings or long-period gratings to modify the optical properties of the radiation beams (5, 6, 7) and/or the interaction thereof with the grating with receptors (11), such that it allows, for example, different optical responses to be obtained.

[0068] The device (18) may also comprise different recognition elements (3), each one having its optical response tuned to a different wavelength, modifying the period of the grating with receptors (11) and/or the inclination thereof with respect to the waveguide (1), or the dimensions of the test area (2), such that they have different and non-overlapping spectral responses in the reflected beam (6) and/or transmitted beam (7), thus allowing different multiple analyses to be conducted in a single sample.

[0069] When needed, multiple test areas (2) can be joined together in series or in parallel, each one with at least one recognition element (3), all of them being tuned to different wavelengths modifying the period of the grating with receptors (11) and/or the inclination thereof with respect to the test area (2) and/or the geometry or composition of the waveguide (1) over the test area (2).

[0070] Each test area (2) thereby has a different spectral response in the reflected beam (6) and/or the transmitted beam (7), thereby allowing multiple analyses to be conducted both in a single sample and in multiple samples.

[0071] Information about the beams during the actual incubation of the sample can be recorded by using the device (18), such that real-time information is obtained about the biorecognition events of the target compound (12), on the basis of which the concentration of the target compound (12) and/or the affinity constants between the receptors (11) and the target compound (12) is determined.