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

• US 8,774,884 B2
• Filed: 01/10/2011
• Issued: 07/08/2014
• Est. Priority Date: 02/10/2010
• Status: Active Grant

• Current Assignee: Tokitae LLC (Intellectual Ventures LLC)
• Original Assignee: Tokitae LLC (Intellectual Ventures LLC)
• Inventors: Behrend, Matthew R., Hegg, Michael C., Horning, Matthew P., Wilson, Benjamin K.
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US12/930,611
• Publication Number:
  US 20110196222A1
• Time in Patent Office: 1,275 Days
• Field of Search: 600/310, 600/322, 600/344, 362/581, 362/232, 362/233
• US Class Current: 600/310
• 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 for providing a monitor or treatment device configured to, for example, detect hemozoin, as well as to monitor or treat a malarial infection.

Claims

1. An apparatus, comprising:

a dark-field illuminator having

a body structure defining at least one aperture,

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 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 scattered electromagnetic energy from a sample interrogated by the dark-field illuminator;

one or more data structures having reference hemozoin response information stored thereon; and

circuitry configured to compare information associated with the capture scattered electromagnetic energy to the reference hemozoin response information stored in the one or more data structures, and determine one or more of a presence, an absence, and a severity of malaria condition based on the comparison.

2. The apparatus of claim 1, wherein individual ones of the plurality of sensors are operably coupled to one or more of the plurality of interrogators to form one or more sensor-interrogator pairs.

3. The apparatus of claim 2, wherein the one or more sensor-interrogator pairs acquire angle-dependent electromagnetic energy scattering information.

4. The apparatus of claim 2, wherein the one or more sensor-interrogator pairs acquire wavelength-dependent electromagnetic energy scattering information.

5. The apparatus of claim 2, wherein individual ones of the plurality of sensors are positioned to capture scattered electromagnetic energy from a sample interrogated by one or more of the plurality of interrogators forming part of the sensor-interrogator pairs.

6. The apparatus of claim 2, wherein individual ones of the plurality of sensors are positioned within an optical path that substantially avoids electromagnetic energy unscattered from a sample interrogated by one or more of the plurality of interrogators forming part of the sensor-interrogator pairs.

7. The apparatus of claim 1, wherein the plurality of interrogators concurrently or sequentially direct at least a first interrogation stimulus and a second interrogation stimulus onto a focal region, the second interrogation stimulus having an angle of incidence different from the first interrogation stimulus.

8. The apparatus of claim 1, wherein the plurality of interrogators concurrently or sequentially direct at least a first interrogation stimulus and a second interrogation stimulus onto a focal region, the second interrogation stimulus having peak emission wavelength different from the first interrogation stimulus.

9. The apparatus of claim 1, wherein the plurality of interrogators concurrently or sequentially provide interrogation stimuli onto two or more focal region locations, at two or more angles of incidence.

10. The apparatus of claim 1, further comprising:

means for adjusting a dark-field illuminator distance relative to an optical assembly along an axis substantially parallel to an optical axis of the optical assembly.

11. The apparatus of claim 1, further comprising:

means for adjusting an angle of incidence of electromagnetic energy emitted by the plurality of interrogators.

12. A malaria detection apparatus, comprising:

an optical assembly having a sample side, a detector side, and an optical axis therethrough;

a dark-field illuminator proximate the sample side of the optical assembly, the dark-field illuminator including

a plurality of waveguide assemblies,

a sensor component including one or more sensors configured to receive scattered electromagnetic energy from a sample interrogated by the dark-field illuminator, and

a body structure having at least one aperture aligned along an axis substantially parallel to an optical axis;

one or more data structures having reference hemozoin nonlinear response information stored thereon; and

circuitry configured to compare information associated with the received scattered electromagnetic energy to reference hemozoin nonlinear response information, and determine one or more of a presence, an absence, and a severity of malaria condition based on the comparison.

13. The malaria detection apparatus of claim 12, wherein the sensor component includes a sensor array to acquire angle-dependent electromagnetic energy scattering information.

14. The malaria detection apparatus of claim 12, wherein the sensor component includes a sensor array to acquire wavelength-dependent electromagnetic energy scattering information.

15. The malaria detection apparatus of claim 12, wherein the plurality of waveguide assemblies include at least a first electromagnetic energy emitter and a second electromagnetic energy emitter, the second electromagnetic energy emitter having a peak emission wavelength different from the first electromagnetic energy emitter.

16. The malaria detection apparatus of claim 12, further comprising:

means for adjusting a dark-field illuminator distance relative to the optical assembly along an axis substantially parallel to an optical axis of the optical assembly.

17. The malaria detection apparatus of claim 12, further comprising:

means for adjusting an angle of incidence of electromagnetic energy delivered by the dark-field illuminator.

18. The malaria detection apparatus of claim 12, further comprising:

a detector configured to capture one or more micrographs associated with the scattered electromagnetic energy from the sample interrogated by the dark-field illuminator.

19. A dark-field illuminator, comprising:

a body structure defining at least one aperture;

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 within the least one aperture at one or more angles of incidence relative to an optical axis of an optical assembly;

a plurality of sensors configured to acquire nonlinear multi-harmonic response information associated with a sample interrogated by the dark-field illuminator;

circuitry configured to

compare information associated with the nonlinear multi-harmonic response information to reference hemozoin nonlinear response configured as a data structure, and

generate a response indicative of one or more of a presence, an absence, and a severity of malaria condition based on the comparison.

20. The dark-field illuminator of claim 19, wherein the plurality of sensors is operably coupled to individual ones of the plurality of interrogators and is configured to acquire angle-dependent electromagnetic energy scattering information.

21. The dark-field illuminator of claim 19, wherein the plurality of sensors is operably coupled to individual ones of the plurality of interrogators and is configured to acquire wavelength-dependent electromagnetic energy scattering information.

22. The dark-field illuminator of claim 19, further comprising:

a coupling structure configured to removably attach the dark-field illuminator to an optical assembly by a bayonet coupling, a friction fit coupling, a snap fit coupling, or a threaded coupling.

23. A dark-field illuminator system, comprising:

an interrogation stimulus circuit configured to direct an electromagnetic energy stimulus onto one or more focal volumes of a sample;

a detection circuit configured to acquire a micrograph of a sample interrogated by the interrogation stimulus circuit at one or more angles of incidence; and

an object identification circuit configure to identify groups of pixels in the micrograph indicative of at least one of a hemozoin nanoparticle or a malaria-infected erythrocyte.

24. The dark-field illuminator system of claim 23, wherein the detection circuit acquires scattered electromagnetic energy from a sample interrogated by the interrogation stimulus circuit at one more azimuthal angles relative to an optical axis.

25. The dark-field illuminator system of claim 23, wherein the detection circuit includes one or more detectors to acquire scattered electromagnetic energy from a sample interrogated by the interrogation stimulus circuit at one or more fields of view and at one or more focal depths.

26. The dark-field illuminator system of claim 23, wherein the interrogation stimulus circuit includes one or more polarizers.

27. The dark-field illuminator system of claim 23, wherein the interrogation stimulus circuit includes one or more polarizer and is configured to direct an electromagnetic energy stimulus having a first polarization onto the one or more focal volumes of the sample.

28. The dark-field illuminator system of claim 23, wherein the detection circuit includes one or more polarizers.

29. The dark-field illuminator system of claim 23, wherein the detection circuit is configured to acquire scattered, depolarized, electromagnetic energy from the sample interrogated by the electromagnetic energy stimulus.