Micro-optical cavity with fluidic transport chip for bioparticle analysis

• US 9,063,117 B2
• Filed: 12/24/2011
• Issued: 06/23/2015
• Est. Priority Date: 02/21/2007
• Status: Active Grant

• Current Assignee: Paul L. Gourley
• Original Assignee: Paul L. Gourley
• Inventors: Gourley, Paul L.
• Primary Examiner(s): TSAI, CAROL S W
• Application Number:
  US13/337,051
• Publication Number:
  US 20150049333A1
• Time in Patent Office: 1,277 Days
• Field of Search: 702/19, 356/154, 356/246, 356/454, 356/318, 372/39, 372/70, 372/50.1, 372/61, 372/101, 422/82.08
• US Class Current: 1/1
• 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 single bioparticles to assess their material condition and health status. The methods are enabled by a resonant cavity to measure optical properties related to the bioparticle size and refractive index. Refractive index measurements are useful for determining material properties and biomolecular composition of the bioparticle. These properties and composition are dependent on the health state of the bioparticle. Thus, measured optical properties can be used to differentiate normal (healthy) and abnormal (diseased) states of bioparticles derived from cells or tissues. The methods are illustrated with data obtained from a resonator with a gain medium. The invention also provides new methods for multiple measurements in a single device, analyzing and manipulating bioparticles that are much smaller than the wavelength of light, and provides a microfluidic transport chip to enable rapid single bioparticle analysis of large populations of bioparticles.

Claims

1. An apparatus for analyzing a bioparticle in an optical cavity, said apparatus comprising:

a light source to establish optical resonance and a standing wave in said optical cavity;

a photodetector for detecting light emitted from the optical cavity;

and the optical cavity comprising;

a fluid transport chip having;

a first surface;

a pair of reservoirs spaced along said first surface, each reservoir recessed into said chip, and a means for transferring fluid among said reservoirs and the exterior of the chip;

an area of the first surface between said reservoirs acting as a barrier between the reservoirs;

an array of one or more channels recessed from the first surface into said barrier and connecting the reservoirs

a first reflective surface on a portion of said channels furthest from the first surface, the chip adjacent to the channels being formed of a material transparent to said light emitted from the optical cavity;

a cover for the channels having;

an inner surface in fluid tight contact with the first surface of the chip;

a second reflective surface, wherein said first and second reflective surfaces define the limits of the optical cavity including the channels; and

an analysis region in the optical cavity.

2. The fluid transport chip of claim 1 wherein said fluid transport chip is formed of at least one material from the group consisting of glass, plastic, semiconductors, polymers, and materials transparent to light of some wavelengths between 200 and 1500 nm.

3. The fluid transport chip of claim 1 wherein said fluid transport chip is further provided with dichroic optical coatings for transmitting pump light wavelengths and reflecting intracavity light.

4. The channels of claim 1 wherein said channels comprise a grated surface in said barrier separating said reservoirs, said grated surface has said channels defined by a plurality of guides with openings substantially parallel to and recessed from said first surface and connecting said pair of reservoirs.

5. The channels of claim 4 wherein the fluid flow in said channels is constricted vertically by said barrier in combination with said cover and laterally by said grated surface comprising said guides with said parallel openings forming said channels.

6. The channels of claim 4 wherein a plurality of said barriers with said grated surface having grates of different dimensions for isolating said bioparticle of a certain size.

7. The cover of claim 1 wherein said cover is further integrated with a light source selected from at least one of the group consisting of a fluorescent material, a semiconductor region including said second reflective surface, a microcavity laser, a semiconductor laser diode, a semiconductor light-emitting diode, and an array of diodes aligned with said array of channels.

8. The cavity of claim 1 wherein said cavity further includes a gain region.

9. The cavity of claim 1 wherein said cavity is a Fabry-Perot cavity.

10. The analysis region of claim 1 wherein said analysis region is defined by at least one selected from the group of a pump laser spot on semiconductor material, a diode light source, a focus of an external laser, a region of a fluorescence material, and a gain region.

11. The cavity of claim 1 wherein said cavity further includes a material structure to define optical modes comprising at least one structure selected from the group consisting of a post, a post array, a triangular lattice of posts, a photonic lattice, and a waveguide.

12. The analysis region of claim 1 wherein said analysis region is located in at least one region selected from the group consisting of center of said channel, a saddlepoint in velocity distribution, a maximum in velocity distribution, an entrance region of said channels, and an exit region of said channels.

14. The cavity of claim 1 wherein the inner surfaces of said cavity are further functionalized to control fluid flow.

15. The cavity of claim 1 wherein said reservoirs have hydraulic conductance 100 times or more higher than the combined hydraulic conductance of all channels.

16. The bioparticle of claim 1 wherein said bioparticle has average concentration of one or less bioparticle per said channel volume to isolate an individual bioparticle in said channel.

17. The cavity of claim 1 wherein a fluid velocity in said channels is adjusted by the external pressure and ratio of reservoir cross sectional area to total channel cross sectional area to control the transit time of said bioparticle across said channel to less than 100 microseconds.

18. The cavity of claim 1 wherein said fluid is a high speed jet of fluid without bioparticles comprising at least one fluid type selected from the group consisting of fluids intended for cleaning, priming, wetting, and coating with molecular layers the inner surfaces of said cavity.

19. The cavity of claim 1 wherein said reflective surfaces are structures comprising at least one structure selected from the group consisting of layers, waveguides, photonic lattices, periodic bandgap materials, and fibers, and said structures comprise at least one material selected from the group of dielectrics, metals, glasses, plastics, semiconductors, and polymers and said structures comprise at least one geometrical form selected from the group of planar, box-like, rod, cylindrical, ring, and spherical.

20. The cavity of claim 1 wherein said cavity comprises an intracavity fluid grate with at least one channel for flow of fluids.

21. The cavity of claim 1 wherein said reflective surfaces comprise parallel planar high reflectors facing each other.

22. The cavity of claim 1 wherein at least one approximate dimension of said cavity is selected from the group consisting of said analysis region, size of said bioparticle, the wavelength of said standing wave, and a dimension in the range 100 to 3000 nanometers.

23. The cavity of claim 1 wherein at least one surface of said cavity is provided with a layer to enhance said cavity properties including at least one property selected from the group consisting of biocompatible, optical, fluidic, mechanical and electrical.

24. The light source of claim 1 wherein at least one light source is selected from the group consisting of optical pumping and electrical injection.

25. The cavity of claim 1 wherein said cavity is includes at least one element selected from the group consisting of a semiconductor, a fluorescent material, a microcavity laser structure, a nanolaser, a photonic lattice, a photonic nanostructure, quantum dots, quantum arrays, quantum wires, and quantum layers.

26. The photodetector of claim 1 wherein said photodetector uses machine vision for detection and analysis of at least one measured property selected from the group consisting of, a spectrum, a wavelength, a linewidth, an intensity, a polarization, an image, a position, a size, a morphology, a refractive index, a polarizability, and a statistical property.

13. The cavity of 1 wherein said tight contact between the chip and cover uses a least one sealing method selected from the group of optical contact, intimate physical contact, surface tension, mechanical pressure, chemical, and o-ring.