Analysis of bioparticles in an optical microcavity

• US 9,766,223 B2
• Filed: 05/08/2015
• Issued: 09/19/2017
• Est. Priority Date: 02/20/2008
• Status: Active Grant

• Current Assignee: Paul L. Gourley
• Original Assignee: Paul L. Gourley
• Inventors: Gourley, Paul L.
• Primary Examiner(s): Tsai, Carol S
• Application Number:
  US14/708,064
• Publication Number:
  US 20150316464A1
• Time in Patent Office: 865 Days
• Field of Search: 702 19, 356511, 356515, 356491, 356496, 356450, 356485, 356502, 356318, 356338
• CPC Class Codes: G01N 15/1404 Handling flow, e.g. hydrodynamic focusing
• CPC Class Codes: G01N 15/1409 Handling samples, e.g. injecting samples
• CPC Class Codes: G01N 15/1436 the optical arrangement forming an integrated apparatus with the sample container, e.g. a flow cell
• CPC Class Codes: G01N 15/1484 microstructural devices
• CPC Class Codes: G01N 2015/1006 for cytology
• CPC Class Codes: G01N 2015/1493 Particle size
• CPC Class Codes: G01N 2015/1495 Deformation of particles
• CPC Class Codes: G01N 21/47 Scattering, i.e. diffuse reflection G01N21/25, G01N21/41 take precedence G01N21/55 takes precedence
• 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 21/7746 the waveguide coupled to a cavity resonator
• CPC Class Codes: G01N 33/4833 of solid biological material, e.g. tissue samples, cell cultures tissue in vivo A61B5/00; cell suspensions G01N33/48735
• CPC Class Codes: G01N 33/574 for cancer

Abstract

This invention provides new methods and apparatus for rapidly analyzing a single bioparticle or a plurality of bioparticles to assess their condition. The invention is enabled by an optical microcavity comprising reflective structures to confine light and bioparticles in the same space. Under resonance conditions, an electromagnetic standing wave is established in the microcavity to interact with the bioparticle. Means are provided to bring a bioparticle into the microcavity and to detect changes in the resonance condition with and without the bioparticle in the microcavity. Information about the bioparticle is obtained using the benefits of light interactions as fast, non-contacting, and non-destructive.

Claims

1. An apparatus for bioparticle analysis comprising:

an optical cavity with highly reflective structures arranged to confine light within a space;

a light source to provide a resonance condition with a periodic electromagnetic field in a standing wave in said cavity;

a photodetector to detect said resonance condition using light emitted from the cavity;

a means to locate a bioparticle in the cavity; and

means to detect differences or fluctuations in said light emitted from the cavity due to interaction of said bioparticle with said standing wave,

whereby information about the bioparticle can be obtained and transformed to an output display.

2. The cavity of claim 1 wherein said cavity is graded in space to provide interference fringes of at least one type selected from the group consisting of spaced interference fringes, intensity maxima that occur as contours, transmitted light, and reflected light.

3. The photodetector of claim 1 wherein said photodetector further includes machine vision for analyzing at least one of the group consisting of cavity fringes, fringe displacement by bioparticle, bioparticle image, spectral position, spectral linewidth, intensity, and wavelength.

4. The apparatus of claim 1 further including a means to modulate or scan said cavity or said light source.

5. The apparatus of claim 1 wherein said apparatus operates in at least one regime selected from the group consisting of the geometrical limit, the Rayleigh limit, and the Mie regime, according to the ratio of the wavelength of said standing wave to the radius of said bioparticle.

6. The bioparticle of claim 1 wherein said bioparticle has size about 200 to 500 nm to provide nano-squeezed light.

7. The optical cavity to confine light within a space of claim 1 wherein said space has a dimension less than about one micron to provide said standing wave in the cavity with 10 or fewer antinodes.

8. The cavity of claim 1 wherein at least one surface of said cavity is recessed to confine or flow fluids.

9. The cavity of claim 1 wherein said cavity is provided with a means of optical gain.

10. The light emitted from said cavity of claim 1 wherein said light is at least one type of light selected from the group consisting of coherent light, incoherent light, scattered light, and fluorescence.

11. The light emitted from said cavity of claim 1 wherein said light is detected as a function of at least one variable selected from the group consisting of time, frequency, and angle emitted.

12. The light emitted from the cavity of claim 1 wherein said light includes at least one type selected from the group consisting of light fluctuations, dynamic light scattering, correlation spectra, and spectral linewidth to provide information about bioparticle dynamics.