Systems, devices, and methods including a dark-field reflected-illumination apparatus

• US 20110222059A1
• Filed: 02/04/2011
• Published: 09/15/2011
• Est. Priority Date: 02/10/2010
• Status: Active Grant

• Current Assignee: Tokitae LLC (Intellectual Ventures LLC)
• Original Assignee: Tokitae LLC A Limited Liability Company of The State of Delaware
• Inventors: Horning, Matthew P., Wilson, Benjamin K., Hegg, Michael C., Behrend, Matthew R.
• Granted Patent: US 8,854,622 B2
• Time in Patent Office: Days
• US Class Current: 356/317
• CPC Class Codes: A61B 2562/0238 Optical sensor arrangements for performing transmission measurements on body tissue
• CPC Class Codes: A61B 3/1233 for measuring blood flow, e.g. at the retina
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/0062 Arrangements for scanning
• CPC Class Codes: A61B 5/05 Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves impedance plethysmography A61B5/0295; measuring movement of the entire body or parts thereof A61B5/11; detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof A61B5/24
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/48 Other medical applications
• CPC Class Codes: A61B 8/06 Measuring blood flow measuring volume flow in general G01F, e.g. G01F1/66, G01F1/72; measuring speed of fluids in general G01P5/00
• CPC Class Codes: A61N 2/004 specially adapted for a specific therapy
• CPC Class Codes: G01N 21/00 Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light G01N3/00 - G01N19/00 take precedence
• CPC Class Codes: G01N 21/49 within a body or fluid
• CPC Class Codes: G01N 2333/445 Plasmodium
• CPC Class Codes: G02B 21/10 affording dark-field illumination G02B21/14 and G02B21/125 take precedence
• CPC Class Codes: G02B 21/361 Optical details, e.g. image relay to the camera or image sensor G02B21/364 takes precedence; illumination details G02B21/06 and subgroups
• CPC Class Codes: G02F 1/1313 specially adapted for a particular application
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Systems, devices, and methods are described that modulate a specimen-background dark-field micrograph contrast.

Claims

1. A dark-field detection system, comprising:

an illumination angle controller that modulates an angle of incidence of electromagnetic energy delivered by a dark-field illuminator, the dark-field illuminator oriented to focus electromagnetic energy onto at least one focal region of a sample, at one or more angles of incidence relative to an optical axis of an optical assembly;

an aperture controller operably coupled to an aperture device, the aperture controller operable to modulate an effective numerical aperture associated with a collection zone of scattered electromagnetic energy from the sample interrogated by the electromagnetic energy delivered by the dark-field illuminator; and

an illumination-collection separation controller operably coupled to the illumination angle controller and the aperture controller, the illumination-collection separation controller configured to vary an illumination-collection spacing, bounded in part by the electromagnetic energy delivered by the dark-field illuminator and the collection zone, by actuating at least one of the illumination angle controller or the aperture controller.

2. The dark-field detection system of claim 1, wherein the illumination angle controller includes a computing device operably coupled to one or more waveguide assemblies of the dark-field illuminator, the one or more waveguide assemblies configured to change an angle of incidence of electromagnetic energy delivered by the dark-field illuminator in response to an applied current.

3. The dark-field detection system of claim 1, wherein the illumination angle controller includes at least one of an electro-mechanical component, an opto-mechanical component, an electro-optic component, or an acousto-optic component, the at least one of the electro-mechanical component, the opto-mechanical component, the electro-optic component, or the acousto-optic component configured to change an angle of incidence of electromagnetic energy delivered by the dark-field illuminator when activated.

4. The dark-field detection system of claim 1, wherein the illumination angle controller includes a computing device operably coupled to an optical waveguide configured to change an angle of incidence of electromagnetic energy delivered by one or more of a plurality of waveguide assemblies forming part of the dark-field illuminator.

5. The dark-field detection system of claim 1, wherein the aperture controller modulates the effective numerical aperture associated with a collection zone by manipulating a plurality of pixels of a liquid crystal display device associated with the aperture device.

6. The dark-field detection system of claim 1, wherein the aperture controller is configured to modulate a numerical aperture associated with a collection zone, the collection zone defined as a cone having a half-angle α

_c determine by the expression

NA(numerical aperture)=n*sin(α

_c), where

n is the refractive index of a medium found between a lens of a collection objective and the sample, and

α

_c is the one-half angular aperture of the collection objective.

7. The dark-field detection system of claim 1, wherein the aperture controller modulates the effective numerical aperture associated with a collection zone by varying an aperture diaphragm device.

8. The dark-field detection system of claim 1, wherein the aperture controller varies the effective numerical aperture associated with a collection zone by varying an iris dimension.

9. The dark-field detection system of claim 1, wherein the aperture controller includes a computing device operably coupled to an electronic aperture, and configure to vary an effective numerical aperture associated with the electronic aperture based on a target intensity difference.

10. The dark-field detection system of claim 1, wherein the aperture controller includes a computing device operably coupled to one or more tunable optic components.

11. The dark-field detection system of claim 1, wherein the aperture controller includes a computing device operably coupled to an objective-sample interface component having a tunable refractive index.

12. The dark-field detection system of claim 1, wherein the illumination-collection separation controller includes a computing device operably coupled to the dark-field illuminator and a collection objective aperture, the computing device configured to vary an illumination-collection spacing by actuating at least one of the illumination angle controller or the aperture controller based on a contrast differential.

13. A method of modulating a specimen-background dark-field micrograph contrast, comprising:

varying an illumination-collection spacing by varying at least one of an illumination angle of incidence or a collection aperture dimension based on a detected contrast differential.

14. The method of modulating the specimen-background dark-field micrograph contrast of claim 13, wherein varying the illumination-collection spacing includes concurrently varying the illumination angle of incidence and the collection aperture dimension.

15. The method of modulating the specimen-background dark-field micrograph contrast of claim 13, wherein varying the illumination-collection spacing includes modulating a separation zone bounded in part by an electromagnetic energy delivered by a dark-field illuminator and a sample-scattering collection zone associated with an effective numerical aperture of an objective assembly.

16. The method of modulating the specimen-background dark-field micrograph contrast of claim 13, wherein varying the effective collection angle includes modulating a numerical aperture associated with a scattered electromagnetic energy collection objective.

17. The method of modulating the specimen-background dark-field micrograph contrast of claim 13, wherein varying the collection aperture dimension includes modulating an effective numerical aperture associated with a scattered electromagnetic energy collection objective.

18. The method of modulating the specimen-background dark-field micrograph contrast of claim 13, wherein varying the collection aperture dimension includes manipulating a plurality of pixels of a liquid crystal display device.

19. The method of modulating the specimen-background dark-field micrograph contrast of claim 13, wherein varying the collection aperture dimension includes actuating an electronic aperture based on a target intensity threshold difference.

20. The method of modulating a specimen-background dark-field micrograph contrast of claim 13, further comprising:

varying one of the illumination angle or the collection aperture dimension while maintaining a substantially fixed illumination-collection spacing.

21. An apparatus, comprising:

a plurality of interrogators each comprising a waveguide assembly including one or more electromagnetic energy waveguides configured to be coupled to at least one electromagnetic energy emitter, the plurality of interrogators oriented to focus electromagnetic energy onto at least one focal region at one or more angles of incidence relative to an optical axis of an optical assembly;

a collection aperture device having a controllable effective numerical aperture associated with a sample-scattering collection zone;

an illumination-collection separation controller operably coupled to one or more of the plurality of interrogators and to the collection aperture device, the illumination-collection separation controller configured to modulate a separation zone defined by an electromagnetic energy delivered by the dark-field illuminator and the sample-scattering collection zone.

22. The apparatus of claim 21, wherein the collection aperture device includes one or more electronic shutters, programmable shutters, or liquid crystal display shutters.

23. The apparatus of claim 21, wherein the illumination-collection separation controller is configured to modulate the separation zone by varying an orientation of electromagnetic energy delivered by at least one of the plurality of interrogators.

24. The apparatus of claim 21, wherein the illumination-collection separation controller includes a computing device operably coupled to an electronic aperture associates with the collection aperture device, the computing device configured to actuate the electronic aperture based on a target contrast differential.

25. A malaria detection method, comprising:

interrogating one or more focal volumes of a biological sample with an electromagnetic energy stimulus having a first polarization;

acquiring scattered electromagnetic energy from the biological sample interrogated by the electromagnetic energy stimulus, the acquired scattered electromagnetic energy having a polarization different from the first polarization;

generating a first filtered micrograph by filtering the acquired scattered electromagnetic energy based on a filtering protocol; and

determining a disease state by identifying objects of the biological sample in the first filtered micrograph.

26. The malaria detection method of claim 25, wherein acquiring the scattered electromagnetic energy from the biological sample includes acquiring the scattered electromagnetic energy via a sensor component having one or more crossed polarizers.

27. The malaria detection method of claim 25, wherein acquiring the scattered electromagnetic energy from the biological sample includes acquiring the scattered electromagnetic energy via a sensor component having one or more orthogonal polarizers.

28. The malaria detection method of claim 25, wherein interrogating the one or more focal volumes of a biological sample includes delivering electromagnetic energy through a plurality of waveguide assemblies onto at least one focal region at one or more angles of incidence relative to an optical axis of an optical assembly.

29. An apparatus, comprising:

a dark-field illuminator having

a body structure defining at least one aperture, and

a plurality of interrogators each comprising a waveguide assembly including one or more electromagnetic energy waveguides configured to be coupled to at least one electromagnetic energy emitter, the plurality of interrogators oriented to focus electromagnetic energy having a first polarization onto at least one focal region within the least one aperture at one or more angles of incidence relative to an optical axis of an optical assembly; and

a plurality of sensors configured to capture electromagnetic energy having a second polarization from a sample interrogated by the dark-field illuminator.

30. The apparatus of claim 29, wherein the dark-field illuminator includes one or more polarizers.

31. The apparatus of claim 29, wherein the dark-field illuminator includes at least one of a linear polarizer, a circular polarizer, or a crossed polarizer.