Integrated waveguide structure for fluorescence analysis

• US 9,816,935 B2
• Filed: 01/23/2015
• Issued: 11/14/2017
• Est. Priority Date: 01/23/2014
• Status: Active Grant

• Current Assignee: IMEC International
• Original Assignee: IMEC International
• Inventors: Peumans, Peter, Van Dorpe, Pol
• Primary Examiner(s): Pak, Sung
• Application Number:
  US15/113,122
• Publication Number:
  US 20170003227A1
• Time in Patent Office: 1,026 Days
• Field of Search: None
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 2021/7716 in cladding
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates
• CPC Class Codes: G01N 21/648 using evanescent coupling or surface plasmon coupling for the excitation of fluorescence
• CPC Class Codes: G01N 21/7746 the waveguide coupled to a cavity resonator
• CPC Class Codes: G02B 2006/12147 Coupler
• CPC Class Codes: G02B 6/00 Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings
• CPC Class Codes: G02B 6/1223 high refractive index type, i.e. high-contrast waveguides
• CPC Class Codes: G02B 6/1228 Tapered waveguides, e.g. integrated spot-size transformers for coupling with fibres G02B6/305
• CPC Class Codes: G02B 6/125 Bends, branchings or intersections
• CPC Class Codes: G02B 6/4214 the intermediate optical element having redirecting reflective means, e.g. mirrors, prisms for deflecting the radiation from horizontal to down- or upward direction toward a device G02B6/4246 takes precedence

Abstract

The present disclosure relates to structures, systems, and methods for characterizing one or more fluorescent particles. At least one embodiment relates to an integrated waveguide structure. The integrated waveguide structure includes a substrate. The integrated waveguide structure also includes a waveguide layer arranged on top of the substrate. The waveguide layer includes one or more excitation waveguides, one or more emission waveguides, and a particle radiation coupler, which includes a resonator element. In addition, the integrated waveguide structure includes one or more sensing sites configured with respect to the one or more excitation waveguides and the one or more emission waveguides such that a fluorescent particle at one of the sensing sites is activated by an excitation radiation transmitted via the one or more excitation waveguides and radiation emitted by the fluorescent particle is coupled into at least one of the emission waveguides by the particle radiation coupler.

Claims

1. An integrated waveguide structure, comprising:

a substrate;

a waveguide layer arranged on top of the substrate, the waveguide layer comprising;

one or more excitation waveguides configured to transmit excitation radiation to activate a fluorescent particle;

one or more emission waveguides, distinct from the one or more excitation waveguides, configured to transmit radiation emitted by the fluorescent particle; and

a particle radiation coupler, wherein the particle radiation coupler comprises a resonator element arranged to couple radiation emitted by the fluorescent particle into at least one of the emission waveguides in response to the activation by the excitation radiation transmitted via the one or more excitation waveguides; and

one or more sensing sites configured with respect to the one or more excitation waveguides and the one or more emission waveguides such that a fluorescent particle at one of the sensing sites is activated by the excitation radiation transmitted via the one or more excitation waveguides and radiation emitted by the fluorescent particle is coupled into at least one of the emission waveguides by the particle radiation coupler,

wherein the resonator element is positioned between at least one of the emission waveguides and at least one of the excitation waveguides, and

wherein at least one of the sensing sites is positioned between at least one of the excitation waveguides and the resonator element.

2. The integrated waveguide structure according to claim 1,

wherein the integrated waveguide structure further comprises a sensing layer arranged on top of the waveguide layer, wherein the one or more sensing sites are on top of the sensing layer, and

wherein the one or more sensing sites are disposed in a cavity in the sensing layer or in a cavity extending through the sensing layer and into the waveguide layer.

3. The integrated waveguide structure according to claim 1, wherein the one or more sensing sites are positioned with respect to the one or more excitation waveguides so as to enable the activation of the fluorescent particle by an evanescent field of the excitation radiation propagating through the one or more excitation waveguides.

4. The integrated waveguide structure according to claim 1,

wherein the particle radiation coupler is a disk resonator, a ring resonator, a linear resonator, or a photonic crystal resonator, and

wherein the particle radiation coupler is tuned to couple radiation having a wavelength corresponding to a wavelength of a fluorescence emission of the fluorescent particle.

5. The integrated waveguide structure according to claim 1, wherein the particle radiation coupler is positioned in at least one of the emission waveguides or in a near field region thereof.

6. The integrated waveguide structure according claim 1, wherein at least one of the sensing sites is located above the one or more emission waveguides.

7. The integrated waveguide structure according to claim 1,

wherein a direction of at least one of the excitation waveguides is substantially orthogonal to a direction of at least one of the emissions waveguides, thereby forming crossing waveguides.

8. The integrated waveguide structure according to claim 1,

wherein at least one of the excitation waveguides is connected to at least one of the emission waveguides.

9. The integrated waveguide structure according to claim 7,

wherein the at least one sensing site is positioned above or in the at least one emission waveguide, away from a center of a point of crossing of the crossing waveguides, and

wherein the at least one sensing site is positioned off-center with respect to the at least one emission waveguide.

10. The integrated waveguide structure according to claim 1,

wherein at least one of the excitation waveguides comprises a mode expander, and

wherein the mode expander is positioned at or near at least one of the sensing sites so that excitation radiation at the position of the mode expander can excite the fluorescent particle.

11. The integrated waveguide structure according to claim 1,

wherein the one or more excitation waveguides comprise a plurality of substantially parallel excitation waveguides,

wherein the one or more emission waveguides comprise a plurality of substantially parallel emission waveguides that cross the plurality of substantially parallel excitation waveguides, and

wherein the one or more sensing sites comprise a plurality of sensing sites each located at a crossing of an excitation waveguide and an emission waveguide.

12. The integrated waveguide structure according to claim 1, wherein at least one of the sensing sites has a surface chemistry adapted for capturing the fluorescent particle or at least one of the sensing sites comprises a cavity that is smaller than a wavelength of the excitation radiation.

13. A characterization system for characterizing at least one fluorescent particle, the characterization system comprising:

an integrated waveguide structure, the integrated waveguide structure comprising;

a substrate;

a waveguide layer arranged on top of the substrate, the waveguide layer comprising;

one or more excitation waveguides configured to transmit excitation radiation to activate a fluorescent particle;

one or more emission waveguides, distinct from the one or more excitation waveguides, configured to transmit radiation emitted by the fluorescent particle; and

a particle radiation coupler, wherein the particle radiation coupler comprises a resonator element arranged to couple radiation emitted by the fluorescent particle into at least one of the emission waveguides in response to the activation by the excitation radiation transmitted via the one or more excitation waveguides; and

one or more sensing sites configured with respect to the one or more excitation waveguides and the one or more emission waveguides such that a fluorescent particle at one of the sensing sites is activated by the excitation radiation transmitted via the one or more excitation waveguides and radiation emitted by the fluorescent particle is coupled into at least one of the emission waveguides by the particle radiation coupler,

wherein the resonator element is positioned between at least one of the emission waveguides and at least one of the excitation waveguides, and

wherein at least one of the sensing sites is positioned between at least one of the excitation waveguides and the resonator element;

one or more excitation radiation sources configured to transmit the excitation radiation through at least one of the excitation waveguides; and

one or more detectors configured to detect radiation transmitted by at least one of the emission waveguides.

14. The characterization system according to claim 13, wherein at least one of the detectors is an integrated detector integrated in the at least one of the emission waveguides, or at least one of the excitation radiation sources is an integrated radiation source integrated in the at least one of the excitation waveguides, or at least one of the detectors comprises a rejection filter suitable for rejecting the excitation radiation transmitted by at least one of the excitation waveguides.

15. The characterization system according to claim 13,

wherein the one or more excitation waveguides comprise a plurality of substantially parallel excitation waveguides,

wherein the one or more emission waveguides comprise a plurality of substantially parallel emission waveguides that cross the plurality of substantially parallel excitation waveguides,

wherein the one or more sensing sites comprise a plurality of sensing sites each located at a crossing of an excitation waveguide and an emission waveguide,

wherein the characterization system further comprises excitation facilities for each of the substantially parallel emission waveguides and detection facilities for each of the emission waveguides, and

wherein the characterization system further comprises a controller programmed to sequentially activate different sets of fluorescence particles by sequentially transmitting excitation radiation in the excitation waveguides.

16. The characterization system according claim 13,

wherein the characterization system further comprises a chemical cell, the chemical cell comprising two reservoirs separated by a membrane, the two reservoirs being connected through a nanopore in the membrane,

wherein one of the reservoirs comprises ion-sensitive fluorescent dyes and the other reservoir comprises ions for which the fluorescent dyes are sensitive, and

wherein the chemical cell further comprises an electric field generator configured to induce an electric field over the membrane for inducing an ion flow towards the reservoir with the ion-sensitive fluorescent dyes.

17. The characterization system according to claim 16, wherein at least one of the sensing sites is arranged to sense the ion-sensitive fluorescent dyes influenced by ion flow.

18. The characterization system according to claim 16, wherein at least one of the detectors is adapted to detect a variation in fluorescence of the ion-sensitive fluorescent dyes or the membrane is formed by the integrated waveguide structure.

19. A method for characterizing one or more fluorescent particles, the method comprising:

transmitting excitation radiation into one or more excitation waveguides of an integrated waveguide structure;

activating at least one of the fluorescent particles positioned at a sensing site of the integrated waveguide structure, wherein the sensing site is configured such that a fluorescent particle at the sensing site is activated by the excitation radiation transmitted via at least one of the excitation waveguides and radiation emitted by the fluorescent particle is coupled into an emission waveguide of the integrated waveguide structure;

coupling, by a particle radiation coupler, radiation emitted by the fluorescent particle to the emission waveguide of the integrated waveguide structure, wherein the emission waveguide is distinct from the excitation waveguides,

wherein the particle radiation coupler is a resonator element positioned between at least one of the excitation waveguides and the emission waveguide, and

wherein the sensing site is positioned between at least one of the excitation waveguides and the resonator element; and

detecting radiation emitted by the fluorescent particle and transmitted via the emission waveguide.

20. The method according to claim 19, wherein the fluorescent particles are ion-sensitive fluorescent dyes, and wherein the method further comprises:

generating an ion flow through a nanopore of a membrane towards ion-sensitive fluorescent dyes positioned at the sensing site; and

deriving, based on the detected radiation, a point in time that the ion flow is reduced, which is representative of a particle translocating the nanopore and blocking the ion flow.