Systems, devices, and methods including multi-harmonic optical detection of hemozoin nanoparticles

• US 20110196221A1
• Filed: 02/10/2010
• Published: 08/11/2011
• Est. Priority Date: 02/10/2010
• Status: Active Grant

• Current Assignee: Tokitae LLC (Intellectual Ventures LLC)
• Original Assignee: Searete LLC (Intellectual Ventures LLC)
• Inventors: Myhrvold, Nathan P., Tegreene, Clarence T., Wood, Lowell L. JR., Kare, Jordin T., Wilson, Benjamin K., Hegg, Michael C., Horning, Matthew P.
• Granted Patent: US 8,467,842 B2
• Time in Patent Office: Days
• US Class Current: 600/407
• 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/treatment device configured to, for example, detect hemozoin, as well as to monitor or treat a malarial infection.

Claims

1. A system, comprising:

an energy-emitting component configured to interrogate at least one focal volume with a spatially-patterned pulsed multiplexed electromagnetic energy stimulus;

circuitry configured to detect nonlinear multi-harmonic response energy associated with hemozoin nanoparticles within the at least one focal volume interrogated by the spatially-patterned pulsed multiplexed electromagnetic energy stimulus; and

circuitry configured to compare information associated with the detected nonlinear multi-harmonic response energy to a reference hemozoin response profile.

8. The system of claim 1, wherein the circuitry configured to detect the nonlinear multi-harmonic response energy includes circuitry configured to detect a transcutaneously emitted multi-harmonic photonic response.

9. The system of claim 1, wherein the circuitry configured to detect the nonlinear multi-harmonic response energy includes at least one sensor for detecting nonlinear multi-harmonic response energy associated with at least one of a second harmonic response, a third harmonic response, and a fourth harmonic response elicited by the spatially-patterned pulsed multiplexed electromagnetic energy stimulus.

15. The system of claim 1, wherein the reference hemozoin response profile includes reference hemozoin nanoparticle nonlinear susceptibility information.

16. The system of claim 1, wherein the circuitry configured to detect the nonlinear multi-harmonic response energy includes an optical waveguide assembly and at least one sensor for collecting and detecting via an epi-collection mode at least one of a second harmonic response, a third harmonic response, and a fourth harmonic response elicited by the spatially-patterned pulsed multiplexed electromagnetic energy stimulus.

17. The system of claim 1, wherein the circuitry configured to detect the nonlinear multi-harmonic response energy includes a processor for actively controlling a numerical aperture of an objective lens assembly having a selectively controllable numerical aperture ranging from about 0.5 to about 1.4.

19. The system of claim 1, wherein the circuitry configured to compare the detected nonlinear multi-harmonic response energy to the reference hemozoin response profile includes one or more computer-readable memory media having the reference hemozoin response profile configured as a data structure, the reference hemozoin response profile including at least one of hemozoin nonlinear response information, hemozoin spectral information, and hemozoin nonlinear susceptibility information.

20. The system of claim 1, further comprising:

a transmitter configured to send comparison information associated with a comparison of detected nonlinear multi-harmonic response energy to the reference hemozoin response profile.

22. The system of claim 1, wherein the circuitry configured to compare the detected nonlinear multi-harmonic response energy to the reference hemozoin response profile includes a transceiver configured to receive a request to transmit at least one of hemozoin reference information, in situ detected nonlinear multi-harmonic response energy, and comparison information.

25. The system of claim 1, wherein the circuitry configured to compare the detected nonlinear multi-harmonic response energy to the reference hemozoin response profile includes a transceiver configured to report status information at regular or irregular time intervals.

29. The system of claim 1, wherein the energy-emitting component is configured to concurrently or sequentially interrogate multiple focal volumes with a spatially-patterned, multifocal depth, electromagnetic energy stimulus.

34. The system of claim 1, wherein the energy-emitting component is configured to deliver a spatially-patterned pulsed multiplexed electromagnetic energy stimulus having a resolution [0.61*(peak emission wavelength/numerical aperture)] ranging from about 300 nanometers to about 10 micrometers.

35. The system of claim 1, further comprising:

an objective lens assembly having a numerical aperture ranging from about 0.5 to about 1.4.

37. The system of claim 1, wherein the energy-emitting component includes at least one of a first energy emitter and at least one of a second energy emitter, the at least one second energy emitter having a peak emission wavelength different from the at least one first energy emitter.

40. The system of claim 1, wherein the energy-emitting component is configured to concurrently or sequentially deliver a first pulsed electromagnetic energy stimulus and a second pulse electromagnetic energy stimulus, the second pulsed electromagnetic energy stimulus having a focal depth different from the first pulsed electromagnetic energy stimulus.

47. The system of claim 1, wherein the energy-emitting component includes a lens array configure to deliver a spaced-apart energy stimuli having at least a first region and a second region, the second region having a focal depth different from the first region.

48. The system of claim 1, wherein the energy-emitting component includes a plurality of selectively-actuatable electromagnetic energy waveguides configured to direct an emitted spatially-patterned pulsed multiplexed electromagnetic energy stimulus to one or more regions of the at least one focal volume.

49. The system of claim 1, wherein at least a portion of the energy-emitting component is configured for removable attachment to a biological surface of a biological subject.

51. The system of claim 1, further comprising:

circuitry configured to wirelessly communicate comparison information associated with comparing detected nonlinear multi-harmonic response energy to the reference hemozoin response profile.

52. The system of claim 1, further comprising:

circuitry configured to selectively tune at least one of a wavelength distribution of the spatially-patterned pulsed multiplexed electromagnetic energy stimulus and a wavelength distribution of a collected in situ nonlinear multi-harmonic response.

53. The system of claim 1, further comprising:

circuitry configured to generate a response based least in part on one or more comparisons between detected nonlinear multi-harmonic response energy and the reference hemozoin response profile.

54. The system of claim 1, further comprising:

a controller operably coupled to the energy-emitting component, the controller configured to control at least one parameter associated with a delivery of the spatially-patterned pulsed multiplexed electromagnetic energy stimulus.

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50. (canceled)

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60. A method for detecting a condition associated with plasmodium-infected erythrocytes, comprising:

comparing, via circuitry, a nonlinear multi-harmonic response profile associated with at least one focal volume interrogated with a spatially-patterned pulsed electromagnetic energy stimulus to reference hemozoin nonlinear response information.

65. The method for detecting the condition associated with plasmodium infected erythrocytes of claim 60, further comprising:

generating a response based on the comparison of the detected nonlinear multi-harmonic response energy to the reference hemozoin nonlinear response information.

61-64. -64. (canceled)

66-69. -69. (canceled)

70. A method, comprising:

interrogating at least one focal volume suspected of containing hemozoin, with a spatially-patterned pulsed electromagnetic energy stimulus; and

comparing, using circuitry, information associated with a nonlinear multi-harmonic response of the at least one focal volume suspected of containing hemozoin, to information associated with a reference hemozoin nonlinear response.

71. The method of claim 70, further comprising:

determining, using circuitry, whether the information associated with the nonlinear multi-harmonic response of the at least one focal volume suspected of containing hemozoin, is substantially similar to information associated with the reference hemozoin nonlinear response.

72. The method of claim 70, further comprising:

communicating to a user at least one result of the comparison.

73. A method, comprising:

eliciting a nonlinear multi-harmonic response from hemozoin nanoparticles in a biological tissue within a focal volume by interrogating the focal volume with a pulsed electromagnetic energy stimulus having a resolution [0.61*(peak emission wavelength/numerical aperture)] ranging from about 300 nanometers to about 10 micrometers; and

comparing, using circuitry, the nonlinear multi-harmonic response to reference hemozoin nonlinear response information configured as a physical data structure.

74. The method of claim 73, further comprising:

generating a response based on the comparison of the nonlinear multi-harmonic response to the reference hemozoin nonlinear response information.

75-79. -79. (canceled)

80. A hemozoin-monitoring device, comprising:

a sensor component configured to detect a nonlinear multi-harmonic response profile associated with hemozoin nanoparticles in a biological tissue within multiple focal volumes interrogated by a pulsed electromagnetic energy stimulus;

one or more computer-readable storage media including executable instructions stored thereon that, when executed on a computer, instruct a controller to retrieving from storage one or more parameters associated with reference hemozoin nonlinear response information, and to perform a comparison of a detected nonlinear multi-harmonic response profile to the retrieved one or more parameters; and

a transceiver configured to concurrently or sequentially transmit or receive information.

83. The hemozoin-monitoring device of claim 80, wherein the one or more computer-readable storage media further include executable instructions stored thereon that, when executed on a computer, instruct a controller to determine one or more of a presence, an absence, and a severity of malaria in response to the comparison.

81. (canceled)

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86. A medical diagnostic device, comprising:

circuitry configured to generate a multiplexed pulsed electromagnetic energy stimulus having a peak power ranging from about 400 gigawatts to about 8 terawatts;

circuitry configured to direct the multiplexed pulsed electromagnetic energy stimulus on a plurality of focal volumes in a biological subject; and

circuitry configured to detect a multi-harmonic response associated with a plurality of hemozoin nanoparticles in a biological tissue within one or more of the plurality of focal volumes interrogated by the multiplexed pulsed electromagnetic energy stimulus.

87. The medical diagnostic device of claim 86, wherein the circuitry configured to detect the multi-harmonic response includes at least one epi-direction sensor for detecting, in situ, an emitted multi-harmonic response associated with the plurality of hemozoin nanoparticles in a biological tissue interrogated by the multiplexed pulsed electromagnetic energy stimulus.

88. (canceled)

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90. (canceled)