METHOD AND DEVICE FOR DETECTING MIDDLE EAR

CONTENT AND/OR CONDITION

RELATED APPLICATION

This application claims the benefit of priority under 35 USC § 119(e) of US Provisional Patent Application No. 62/801,115 filed 5 February 2019, the contents of which are incorporated herein by reference in their entirety.

FIELD AND BACKGROUND OF THE INVENTION

The present invention, in some embodiments thereof, relates to ear examination and, more particularly, but not exclusively, to a device and method for detecting middle ear content and/or condition.

US Patent Application Publication No. 2017/0071509 to Pandey et al. discloses“Systems and methods are presented for the diagnosis of middle ear pathological conditions based on spectral signatures. Preferred embodiments provide for detection of one or more analytes from the tympanic membrane. Devices use spectral measurements including spectral imaging to non- invasively identify middle ear pathological conditions including cholesteatoma and acute otitis media by providing real-time information of differentially expressed molecules. Devices and methods can also be used to non-invasively detect and quantify blood analytes from the tympanic membrane.” (Abstract)

US Patent 8602971B2 to Farr discloses“Various embodiments for providing removable and pluggable opto-electronic modules for illumination and imaging for endoscopy or borescopy are provided. Generally, various medical or industrial devices can include one or more solid state or other compact electro-optic illuminating elements located thereon. Additionally, such opto electronic modules may include illuminating optics, imaging optics, image capture devices, and heat dissipation mechanisms. The illumination elements may have different wavelengths and can be time synchronized with an image sensor to illuminate an object for imaging or detecting purpose or otherwise conditioning purpose. The optoelectronic modules may include means for optical and/or wireless communication. The removable opto-electronic modules may be plugged in on the exterior surface of a device, inside the device, deployably coupled to the distal end of the device, or otherwise disposed on the device” (Abstract). SUMMARY OF THE INVENTION

According to an aspect of some embodiments there is provided a device for assessing middle ear content or condition, comprising: a cone shaped body comprising a cylindrical extension at its tapered end, the cylindrical extension having a diameter small enough to be introduced into an external ear canal; a head configured at a wide end of the cone shaped body, the head comprising a plurality of light sources positioned to emit light towards the tympanic membrane when the cylindrical extension is positioned within the external ear canal; the plurality of light sources arranged peripherally around the wide end of the cone shaped body and directed such that the emitted light is transmitted through a solid portion of the cone shaped body; the plurality of light sources configured to emit light independently and sequentially; each of the light sources emitting light at a single wavelength; the cylindrical extension comprising a distally facing imager, the imager equipped with per pixel wide bandpass filters; the device being in communication with circuitry configured to analyze spectral images obtained by the imager to assess middle ear content or condition.

In some embodiments, the imager occupies a volume within the cylindrical extension such that light emitted by the plurality of light sources travels around the imager in a ring shaped pattern. In some embodiments, the circuitry is configured to generate a 2D image of the tympanic membrane using the spectral images.

In some embodiments, the circuitry is programmed to detect fluoroscopic fingerprints of pathogens in the 2D image.

In some embodiments, the imager comprises a CMOS sensor matrix.

In some embodiments, the plurality of light sources comprise between 4-16 LEDs peripherally arranged around the wide end of the cone shaped body.

In some embodiments, each LED emits light at a single wavelength selected from the range of 200-1000 nm, and wherein different LEDs emit light at different wavelengths.

In some embodiments, the circuitry comprises a processor programmed to analyze the spectral images using machine learning techniques.

In some embodiments, the processor is pre-programmed with at least one known fluorescence fingerprint of a pathogen and is configured to compare the spectral image acquired by the imager to the known fluorescence fingerprint.

In some embodiments, the wide bandpass filters are RGB filters and wherein the fluorescence fingerprint is defined by a set of wavelengths that are within wavelength ranges detectable by the RGB filters. In some embodiments, the device comprises 4 light sources, each positioned to illuminate a quadrant area of the tympanic membrane.

In some embodiments, simultaneous activation of all 4 light sources produces a uniform illumination of the tympanic membrane.

In some embodiments, the solid portion of the cone shaped body is formed of a transparent material.

In some embodiments, the circuitry is configured for transferring data to one or more of: a clinician, a database, cloud storage, external memory, a remote server.

In some embodiments, the device comprises a handle extending proximally from the wide end of the cone shaped body.

In some embodiments, the circuitry is in communication with a screen display.

In some embodiments, the cylindrical extension further comprises a set of radio frequency coils and circuity configured for measuring a magnetic field detected in response to passing of electrical current through the coils, the magnetic field indicative of presence of fluid behind the tympanic membrane.

According to an aspect of some embodiments there is provided a method for assessing middle ear content or condition, comprising: emitting light from a plurality of light sources sequentially towards the tympanic membrane; detecting the light returning from the tympanic membrane via an imager equipped with per pixel wide bandpass filters; and processing spectral images acquired by the imager to assess middle ear content or condition.

In some embodiments, the filters comprise RGB filters.

In some embodiments, processing comprises comparing wavelengths of the light returning from the tympanic membrane to expected wavelength ranges.

In some embodiments, comparing comprises comparing to a known set of wavelength values which define a pathogen fingerprint.

In some embodiments, processing comprises generating 2D images of the tympanic membrane from the spectral images.

In some embodiments, each pixel of the 2D image is generated as a combination of K*N spectral images, N being the number of independent light sources from which the light is emitted and K being the number of different wide bandpass filters used.

In some embodiments, processing comprises determining one or more of: a transparency level of the tympanic membrane, a color of the tympanic membrane.

In some embodiments, processing comprises detecting one or both of a fluid level and a viscosity of the fluid behind the tympanic membrane. In some embodiments, the method comprises diagnosing at least one of: acute otitis media (AOM) and otitis media with effusion (OME) according to the pathogen fingerprint.

In some embodiments, the method comprises dividing the tympanic membrane into separately illuminated segments and using a corresponding number of light sources to illuminate the segments.

According to an aspect of some embodiments there is provided a method for identifying pathogens in the middle ear in real time, comprising: illuminating the tympanic membrane using multiple single wavelength light sources; capturing light returning from the tympanic membrane using an imager comprising per-pixel RGB filters; determining presence of one or more pathogens in at least one of middle ear fluid behind the tympanic membrane and the tympanic membrane itself as a function of the light detected by the RGB filters.

In some embodiments, illuminating comprises illuminating at wavelengths which are not detectable by the filters.

In some embodiments, determining comprises comparing a set of wavelengths detected by the filters to a known set of wavelengths that characterizes a pathogen.

In some embodiments, determining comprises comparing to a known fluorescence spectra of enzymes and/or coenzymes and/or amino acids of one or more of: H Influenza, M Cataralis, S Pneumoniae, S. Aureas.

In some embodiments, the method further comprises indicating if a tympanic membrane condition was caused or effected by bacterial growth.

In some embodiments, the method further comprising displaying an image of the tympanic membrane captured by the imager and marking a pathogen distribution on the image.

In some embodiments, the pathogen distribution includes a location of one or more pathogen colonies.

In some embodiments, only light characterized by wavelengths which are detectable by at least one of the RGB filters.

According to an aspect of some embodiments there is provided a method for identifying pathogens in the middle ear in real time, comprising: illuminating the tympanic membrane using multiple single wavelength light sources; capturing light returning from the tympanic membrane using an imager comprising per-pixel RGB filters; wherein if light returning from the tympanic membrane is detected by at least one of the RGB filters, pathogen presence is indicated.

In some embodiments, light returning from the tympanic membrane is detected due to presence of one or more of the following amino acids: Tryptophan, Tyrosine and Phenyloalanine which are characterized by emittance at wavelengths within wavelength ranges detectable by at least one of the RGB filters.

In some embodiments, presence of Tryptophan alone is detected and is indicative of pathogen presence.

According to an aspect of some embodiments there is provided a device for assessing middle ear effusion, comprising: a cone shaped body comprising a cylindrical extension at its tapered end, the cylindrical extension having a diameter small enough to be introduced into an external ear canal; the cylindrical extension comprising co-axial RF coils separated by a diamagnetic insert; and circuitry configured to pass an electrical current through the RF coils and measure a resulting magnetic field; the magnetic field indicative of presence of middle ear fluid.

According to an aspect of some embodiments there is provided a device for assessing middle ear content or condition, comprising: a body which tapers towards a narrow end having a diameter small enough to be introduced into an external ear canal; a plurality of light sources arranged peripherally around the wide end of the body and directed such that the emitted light is transmitted through a solid portion of the body; a distally facing imager for obtaining images of the tympanic membrane; the device being in communication with circuitry configured to analyze spectral images obtained by the imager to assess middle ear content or condition.

In some embodiments, the plurality of light sources are configured to emit light independently and sequentially; each of the light sources emitting light at a single wavelength.

In some embodiments, the imager is equipped with per pixel wide bandpass filters.

In some embodiments, the imager occupies a volume within the cylindrical extension such that light emitted by the plurality of light sources travels around the imager in a ring shaped pattern.

In some embodiments, the circuitry is configured to generate a 2D image of the tympanic membrane using the spectral images.

In some embodiments, the circuitry is programmed to detect fluoroscopic fingerprints of pathogens in the 2D image.

In some embodiments, the imager comprises a CMOS sensor matrix.

In some embodiments, the plurality of light sources comprise between 4-16 LEDs peripherally arranged around the wide end of the cone shaped body, each LED emitting light at a single wavelength selected from the range of 200-1000 nm.

In some embodiments, the circuitry comprises a processor which is pre-programmed with at least one known fluorescence fingerprint of a pathogen and is configured to compare the spectral image acquired by the imager to the known fluorescence fingerprint. In some embodiments, the wide bandpass filters are RGB filters and wherein the fluorescence fingerprint is defined by a set of wavelengths that are within wavelength ranges detectable by the RGB filters.

In some embodiments, the device comprises 4 light sources, each positioned to illuminate a quadrant area of the tympanic membrane.

In some embodiments, simultaneous activation of all 4 light sources produces a uniform illumination of the tympanic membrane.

In some embodiments, the solid portion of the cone shaped body is formed of a transparent material.

In some embodiments, the circuitry is configured for transferring data to one or more of: a clinician, a database, cloud storage, external memory, a remote server.

In some embodiments, the device comprises a handle extending proximally from the wide end of the cone shaped body.

In some embodiments, the circuitry is in communication with a screen display.

In some embodiments, the cylindrical extension further comprises a set of radio frequency coils and circuity configured for measuring a magnetic field detected in response to passing of electrical current through the coils, the magnetic field indicative of presence of fluid behind the tympanic membrane.

According to an aspect of some embodiments there is provided a method for assessing middle ear content or condition, comprising: emitting light from a plurality of light sources sequentially towards the tympanic membrane; detecting the light arriving from the tympanic membrane via an imager equipped with per pixel wide bandpass filters; and processing spectral images acquired by the imager to assess middle ear content or condition.

In some embodiments, the filters comprise RGB filters.

In some embodiments, processing comprises comparing wavelengths of the light arriving from the tympanic membrane to expected wavelength ranges.

In some embodiments, comparing comprises comparing to a known set of wavelength values which define a pathogen fingerprint.

In some embodiments, processing comprises generating 2D images of the tympanic membrane from the spectral images.

In some embodiments, each pixel of the 2D image is generated as a combination of K*N spectral images, N being the number of independent light sources from which the light is emitted and K being the number of different wide bandpass filters used. In some embodiments, processing comprises determining one or more of: a transparency level of the tympanic membrane, a color of the tympanic membrane.

In some embodiments, processing comprises detecting one or both of a fluid level and a viscosity of the fluid behind the tympanic membrane.

In some embodiments, the method comprises diagnosing at least one of: acute otitis media (AOM) and otitis media with effusion (OME) according to the pathogen fingerprint.

In some embodiments, the method comprises dividing the tympanic membrane into separately illuminated segments and using a corresponding number of light sources to illuminate the segments.

According to an aspect of some embodiments there is provided a method for identifying pathogens in the middle ear in real time, comprising: illuminating the tympanic membrane using multiple single wavelength light sources; capturing light arriving from the tympanic membrane using an imager comprising per-pixel RGB filters; determining presence of one or more pathogens in at least one of middle ear fluid behind the tympanic membrane and the tympanic membrane itself as a function of the light detected by the RGB filters.

In some embodiments, illuminating comprises illuminating at wavelengths which are not detectable by the filters.

In some embodiments, determining comprises comparing a set of wavelengths detected by the filters to a known set of wavelengths that characterizes a pathogen.

In some embodiments, determining comprises comparing to a known fluorescence spectra of enzymes and/or coenzymes and/or amino acids of one or more of: H Influenza, M Cataralis, S Pneumoniae, S Aureas.

In some embodiments, the method comprises indicating if a tympanic membrane condition was caused or effected by bacterial growth.

In some embodiments, the method comprises displaying an image of the tympanic membrane captured by the imager and marking a pathogen distribution on the image.

In some embodiments, the pathogen distribution includes a location of one or more pathogen colonies.

In some embodiments, only light characterized by wavelengths which are detectable by at least one of the RGB filters.

According to an aspect of some embodiments there is provided a method for identifying pathogens in the middle ear in real time, comprising: illuminating the tympanic membrane using multiple single wavelength light sources; capturing light arriving from the tympanic membrane using an imager comprising per-pixel RGB filters; wherein if light arriving from the tympanic membrane is detected by at least one of the RGB filters, pathogen presence is indicated.

In some embodiments, light arriving from the tympanic membrane is detected due to presence of one or more of the following amino acids: Tryptophan, Tyrosine and Phenyloalanine which are characterized by emittance at wavelengths within wavelength ranges detectable by at least one of the RGB filters.

In some embodiments, presence of Tryptophan alone is detected and is indicative of pathogen presence.

According to an aspect of some embodiments there is provided a device for assessing middle ear effusion, comprising: a body tapering towards a narrow end having a diameter small enough to be introduced into an external ear canal; at least two RF coils spaced apart from each other; and circuitry configured to pass an electrical current through the RF coils, measure at least one property of each of the coils, and generate an output based on a difference in the measured property between the two coils.

In some embodiments, the at least one property includes: a voltage that develops across the coil, an electromagnetic field generated by the coil, an impedance of the coil.

In some embodiments, the output comprises indicating presence of middle ear fluid based on the difference in the measured at least one property.

In some embodiments, a diamagnetic insert is positioned in between the at least two RF coils along a similar long axis.

According to an aspect of some embodiments there is provided a method for assessing presence of middle ear fluid, comprising: introducing a probe comprising at least two electrically conductive elements into the external ear canal; conducting current through the elements; measuring one or more properties selected from: voltage across each of the elements, an electromagnetic field produced by each of the elements ; and determining a difference in the one or more properties as measured for each of the elements to determine presence of middle ear fluid.

In some embodiments, the method comprises, prior to the introducing, conducting a calibration measurement in which the probe is not in proximity to fluid, and then comparing an electromagnetic field measured inside the external ear canal to the electromagnetic field measured during the calibration measurement.

In some embodiments, comprises positioning a distal end of the probe at a distance of less than 4 mm from the tympanic membrane. In some embodiments, the electrically conductive elements comprise coils and wherein the introducing comprises positioning the coils such that one is axially closer to the tympanic membrane than the other.

According to an aspect of some embodiments there is provided a method for assessing presence of middle ear fluid, comprising: introducing a probe comprising a ultrasound transducer into the external ear canal; excitating the ultrasound transducer to emit ultrasound signals; receiving echoes of the ultrasound signals; and analyzing the echoes to determine a change in echo signal which is indicative of presence of fluid.

In some embodiments, the ultrasound transducer comprises a piezoelectric transducer, the emitting and the receiving are performed using the same piezoelectric transducer.

In some embodiments, introducing comprises positioning the probe such that the ultrasound transducer is in contact with the tympanic membrane or in contact with a liquid or gel medium contacting the tympanic membrane.

According to an aspect of some embodiments there is provided a device for assessing middle ear content or condition, comprising: a body extending between proximal and distal ends, the body sized for insertion, at least in part, into an external ear canal; a plurality of light sources configured at the proximal end of the body, the plurality of light sources facing distally to emit light towards the tympanic membrane when the device is inserted into the external ear canal; a distally facing imager equipped with one or more light filters; and a radio-frequency assembly incorporated within the body and including at least two electrically conductive elements spaced apart from each other.

Unless otherwise defined, all technical and/or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the invention, exemplary methods and/or materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting.

Implementation of the method and/or system of embodiments of the invention can involve performing or completing selected tasks manually, automatically, or a combination thereof. Moreover, according to actual instrumentation and equipment of embodiments of the method and/or system of the invention, several selected tasks could be implemented by hardware, by software or by firmware or by a combination thereof using an operating system. For example, hardware for performing selected tasks according to embodiments of the invention could be implemented as a chip or a circuit. As software, selected tasks according to embodiments of the invention could be implemented as a plurality of software instructions being executed by a computer using any suitable operating system. In an exemplary embodiment of the invention, one or more tasks according to exemplary embodiments of method and/or system as described herein are performed by a data processor, such as a computing platform for executing a plurality of instructions. Optionally, the data processor includes a volatile memory for storing instructions and/or data and/or a non-volatile storage, for example, a magnetic hard-disk and/or removable media, for storing instructions and/or data. Optionally, a network connection is provided as well. A display and/or a user input device such as a keyboard or mouse are optionally provided as well.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

Some embodiments of the invention are herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of embodiments of the invention. In this regard, the description taken with the drawings makes apparent to those skilled in the art how embodiments of the invention may be practiced.

In the drawings:

FIG. 1 is a flowchart of a general method for diagnosing a middle ear content and/or condition, according to some embodiments;

FIG. 2 is a flowchart of a method for diagnosing a middle ear content and/or condition based on spectral images of the tympanic membrane and/or of middle ear fluid behind the tympanic membrane, according to some embodiments;

FIGs. 3A-B are a schematic drawing of a system for diagnosing a middle ear content and/or condition (3A), and a schematic drawing of the path of light through the system (3B), according to some embodiments.

FIG. 4 is a schematic diagram of the process of acquiring and analyzing images of the tympanic membrane, according to some embodiments.

FIG. 5 is a schematic drawing of the human ear;

FIGs. 6A-B are a flowchart of a method for indicating existence of pathogens in the ear using RGB based detection (figure 6A) and a schematic graphic representation of RGB wavelength sensitivity (figure 6B), according to some embodiments; FIGs. 7A-B are examples of images displayed to a user, separately or in combination, according to some embodiments;

FIGs. 8A-F are schematic representations of a device comprising RF coils for diagnosing middle ear effusion, according to some embodiments;

FIG.8G is a flowchart of a method for detecting presence of fluid behind the tympanic membrane using a radio-frequency mechanism, according to some embodiments;

FIGs. 9A-C are images of different views of a 3D-printed model of a human ear used in an experiment performed in accordance with some embodiments;

FIGs. 10A-C are images of the three device probes being tested, arranged on a platform constructed for an experiment performed in accordance with some embodiments;

FIGs. 11A-B show an example of circuitry connecting between the RF and ultrasound modules (11A) and an example of a digital acquisition assembly (11B) for transferring and/or processing of data obtained by the device probe, in accordance with some embodiments;

FIGs. 12A-D show structural and functional details of an ultrasound device probe, according to some embodiments;

FIGs. 13A-B show examples of echo signals recorded by a digital scope when no fluid was injected in the model (FIG. 13A) and when fluid was present (FIG. 13B), in the experiment performed according to some embodiments;

FIG. 13C shows an exemplary screen of a user interface, showing the recorded echo signal and a Fourier transformation of the signal performed in accordance with some embodiments;

FIGs. 14A-E show structural and functional details of a light based device probe, according to some embodiments;

FIGs. 15A is an image of the device and the user interface screen as used in the experiment performed in accordance with some embodiments;

FIGs. 15B-C show examples of the images captured by the light based probe, where in FIG. 15A there was no fluid in the model, and in FIG. 15B fluid was injected in the model;

FIGs. 16A-D show structural and functional details of a radio-frequency based device probe, according to some embodiments;

FIGs. 17A-D show an exemplary experimental setup and results in which an RF probe was tested in accordance with some embodiments;

FIG. 18 is a block diagram of an integrated device, according to some embodiments;

FIG. 19 shows an exemplary light based probe structure, according to some embodiments; FIG. 20 shows an exemplary ultrasound probe structure, according to some embodiments; and

FIG. 21 shows an exemplary RF probe structure, according to some embodiments.

DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION

The present invention, in some embodiments thereof, relates to ear examination and, more particularly, but not exclusively, to a device and method for detecting middle ear content and/or condition.

A broad aspect of some embodiments relates to detection of middle ear content, for example assessment of the presence of middle ear fluid, by measurements obtained from the tympanic membrane.

An aspect of some embodiments relates to detecting middle ear content and/or condition by illuminating the tympanic membrane and detecting the light returning from the tympanic membrane using wide bandpass filters. In some embodiments, the tympanic membrane is illuminated by a plurality of independent light sources. Optionally, each light source is operated to emit light at a distinct wavelength, selected for example from the range of 200-1000 nm. In some embodiments, light returning from the tympanic membrane in response to the illumination is captured. In some embodiments, light is captured by an imager comprising a sensor matrix, for example a CMOS sensor matrix, in which each pixel-sensor is equipped with wide bandpass filters. In an example, each sensor is equipped with RGB filters.

In some embodiments, an image of the tympanic membrane is generated and further processed for determining, for example, characteristics of the tympanic membrane (color, structure (e.g. bulging), transparency level, rupturing, and/or others); middle ear fluid (e.g. fluid level and/or fluid viscosity); and/or other middle ear conditions. In some embodiments, processing involves comparing wavelengths of the light returning from the tympanic membrane to expected wavelength ranges. Optionally, non-matching wavelengths are filtered, potentially improving a sensitivity of detection.

In some embodiments, the imager properties are suitable for capturing of images of the tympanic membrane, optionally from within the ear canal. In some embodiments, properties such as a focal length of the imager, a depth of field of the imager and/or other are selected according to an expected distance range between the imager, when positioned in the ear canal, and the tympanic membrane and/or its surroundings (such as a distance from middle ear fluid, if present). In an example, a depth of field of the imager is between 0.1-4 mm, 0.05- 2 mm, 0.5mm-9 mm, or intermediate, longer or shorter distance. In some embodiments, the generated image of the tympanic membrane is displayed to a user (e.g. a physician). Optionally, the displayed image includes markings for the findings that were automatically identified during processing. Examples of markings that can be laid out onto the image of the tympanic membrane may include: bacterial growth and/or distribution; an indication of rupturing of the membrane; an indication of discoloring of the membrane.

An aspect of some embodiments relates to detecting existence of pathogens in the middle ear as a function of light arriving from the tympanic membrane in response to illumination. In some embodiments, the arriving light is detected by an imager comprising per-pixel wide bandpass filters, such as RGB filters. In some embodiments, when one or more pathogens exist in the ear, the light arriving from the tympanic membrane may be characterized by a set of wavelengths that fall within wavelength ranges that are detectable by the filters, so that detection itself may provide an indication for pathogen presence. In some embodiments, pathogen presence is indicated if light of specific characteristics arrived from the tympanic membrane and detected by the imager with the per-pixel wide band pass filters, such as RGB filters. In the example of RGB filters, detection of light arriving from the tympanic membrane by one, two or all three filters may itself provide a sufficient indication for existence of pathogens.

In some embodiments, the spectra is compared to one or more known sets of wavelengths which are associated with respective one or more pathogens. In an example, pathogens such as H. Influenzae, S. pneumoniae, S. aureus, M. catarrhalls are detected and optionally differentiated according to their known spectra. In some embodiments, the spectra is of one or more amino acids which are present in bacteria, such as Tryptophan, Tyrosine and/or Phenyloalanine. In some cases, the same amino acid found in different pathogen types may be characterized not by a specific wavelength but rather by a wavelength range; optionally, when at least a portion of that wavelength range is detected after the light had passed through the one or more filters, an indication of pathogen existence is provided. In some embodiments, if the spectra is characterized by wavelengths that are above a minimal threshold and below a maximal threshold - detection itself may be indicative of pathogen presence.

In some embodiments, wavelengths of the illumination light are selected from within ranges that are not detectable by the filters, so that the filters are“blind” to the illumination wavelengths. Additionally or alternatively, one or more filters are applied to the light sources (such as on the light source end and not on the imager).

In some embodiments, pathogen detection and optionally identification is carried out by comparing a spectral image obtained by the filter-equipped imager to a database or library of known spectral images associated with specific pathogens. An aspect of some embodiments relates to a device for examining the middle ear, the device comprising a cone shaped body through which light travels distally to illuminate the tympanic membrane, when the device is introduced into the external ear canal. In some embodiments, a plurality of independent light sources (e.g. LEDs), optionally monochromatic, are positioned at or proximally to a proximal wide end of the cone shaped body. In some embodiments, an extension shaped and/or sized to be introduced into the ear canal extends distally from the distal (tapered) end of the cone shaped body. In some embodiments, an imager is positioned within the extension at a location suitable to capture the light arriving from the direction of the tympanic membrane. Optionally, the imager occupies a certain volume of the extension such that the transmitted light bypasses the imager, for example travelling around the imager in a ring shaped pattern.

In some embodiments, in operation, light emitted sequentially by the plurality of light sources is transmitted directly through the solid material from which the peripheral walls of the cone body are formed of. In some embodiments, the material is transparent. In some embodiments, light is transmitted through the solid material such that less than 10%, less than 5%, less than 2% of the emitted light is scattered or reflected.

In some embodiments, a device extension (also referred to as probe) is tapering, for example, being shaped as a hollow cone. In some embodiments, the device extension includes a light conducting channel extending along the length of the cone, optionally along a central axis of the cone. In some embodiments, the cone is shaped and configured to prevent light emitted by the plurality of light sources from exiting the side walls of the cone, for example, the cone is coated by a black light-blocking layer on its inner walls. In some embodiments, the light conducting channel is semitransparent.

In some embodiments, a light conducting channel is not used, and light is transferred through the cone itself (for example, through a center of the cone and/or through walls of a transparent or semi-transparent cone). Optionally, in this construction, the cone is not coated by an inner light-blocking layer.

An aspect of some embodiments relates to identifying pathogens in the middle ear in real time. In some embodiments, an image of the tympanic membrane is generated (for example using devices as described herein) and analyzed for existence of fluoroscopic fingerprints of pathogens, for example of pathogens that exist in the middle ear fluid behind the tympanic membrane and/or on the tympanic membrane. Parameters such as pathogen type, concentration, location, may be assessed. In some embodiments, based on the observation of pathogens, inflammation of the middle ear is determined. In some embodiments, generation of an image and analysis of the image are performed in real time, so that during examination of the ear, a user (e.g. a physician or other clinical personnel) is provided with immediate results. A potential advantage of immediate identification of pathogens in the ear may include assisting the physician in deciding on suitable treatment. For example, prescribe antibiotics according to type of bacteria found, avoid prescribing unneeded medication (for example if no pathogens are found), and decide on quantities and/or duration of medication needed as a function of the amount of bacterial growth.

An aspect of some embodiments relates to a device and/or method for detection of middle ear effusion using radio-frequency. In some embodiments, current is conducted through electrically conductive elements, such as coils, and one or more parameters are assessed for determining or estimating presence of fluid behind the tympanic membrane. Such parameters may include, for example, an electromagnetic field generated by the coil(s) and/or voltage across each of the coils and/or a voltage difference between the coils.

In some embodiments, detection of middle ear effusion using RF comprises positioning spaced apart conductive elements such that a first conductive element is positioned at distance from the tympanic membrane which is shorter than a distance between the second conductive element and the tympanic membrane. In some embodiments, parameters of the electric field produced by each of the elements are affected by the distance from the tympanic membrane, and/or affected by the presence of fluid behind the tympanic membrane. In some embodiments, a capacitive coupling between the conductive elements is measurable. In some embodiments, a permittivity and/or permeability of electromagnetic field(s) produced by the conductive element(s) are assessed.

In some embodiments, a cylindrical extension of a device comprises a set of RF coils separated apart from each other, optionally by a diamagnetic insert. In use, the cylindrical extension is positioned adjacent the tympanic membrane, and electrical current is passed through the coils. By measuring the resulting magnetic field, an indication of existence of middle ear fluid can be provided. In some embodiments, one or more calibration measurements are performed when the device extension (also referred to as“probe”) is positioned at a location in which no fluid is present, for example outside of the ear or at only entry to the external ear canal. Then, in some embodiments, a measurement obtained from adjacent the tympanic membrane is compared to the calibration measurement, and differences in the measured electromagnetic fields may be indicative of presence of fluid. In some embodiments, the two coils along a similar long axis, optionally being a long axis of the probe inserted into the ear. In use, current is conducted through each of the coils. A voltage difference develops along each of the coils (between a first end of the coil and the second opposite end of the coil), and that voltage is measured. In some embodiments, presence of fluid in proximity of the coil affects the voltage, so that upon measuring, a voltage measured for the coil which is at a more distal position and closer to the tympanic membrane would be different from the voltage measured for the more proximal coil, which is positioned further away from the tympanic membrane. Therefore, in some embodiments, if the voltages of both coils are similar (or are within a predefined limited range), this implies that no fluid is present behind the ear; and if the voltages are different, this implies that fluid may be present behind the tympanic membrane. In some embodiments, the proximal coil is used as a reference for defining a baseline electromagnetic field measured in a surrounding in which no fluid exists.

In some embodiments, a diamagnetic insert configured in between the two coils is suitable for electrically isolating the coils and/or for reducing or preventing an effect of ear fluid, if present, on the more proximal (reference) coil.

In some embodiments, an RF probe may be moved axially within the external ear canal (e.g. back and forth) to adjust a distance of the coils from the tympanic membrane. In some embodiments, an RF probe may be moved laterally along the tympanic membrane external surface. Optionally, lateral movement may provide for mapping a plurality of electric fields to potentially assess an amount of fluid (e.g. a fluid level) behind the membrane.

In some embodiments, an antenna of a size small enough to be inserted into the external ear canal is provided. For example, an antenna having a diameter between 0.5-3 mm. In some embodiments, the antenna is configured to transmit and receive radio waves to and from the tympanic membrane, when inserted into the ear.

An aspect of some embodiments relates to a device and/or method for detection of middle ear effusion using ultrasound. In some embodiments, ultrasound signals are emitted towards the tympanic membrane, for example by an ultrasound emitter such as a piezoelectric transducer. In some embodiments, the piezoelectric transducer is configured within a device extension insertable into the external ear canal, allowing for positioning the transducer in contact with the tympanic membrane. In some embodiments, excitation of the transducer causes ultrasound signals to be emitted towards the membrane. Then, in some embodiments, the returning echo signals are received and analyzed for detecting the presence of fluid, amount of fluid, and/or a viscosity of the fluid. In some embodiments, a time delay in the returning echo is correlated with an amount of fluid: optionally, a longer delay is indicative of a larger amount of fluid. In some embodiments, a higher signal attenuation coefficient of the fluid is indicative of a higher viscosity of the fluid. In some embodiments, a single transducer is used for both emitting the ultrasound signals and for receiving the returning echoes. Alternatively, multiple transducers are used, optionally at least one transducer for emitting signals and at least one transducer for receiving returning echoes.

In some embodiments, if no fluid is present behind the tympanic membrane, the emitted signals are returned only by the tympanic membrane. If fluid is present, the emitted signals travel through the fluid medium and are optionally reflected back by the one or more bones behind the tympanic membrane (the malleus, incus and stapes). The attenuation of the signals by the fluid medium may be indicative of the presence of fluid, type of fluid, amount of fluid and/or viscosity of the fluid.

In some embodiments, the ultrasound signals are emitted in pulses. Optionally, a pulse is as short as possible yet sufficient for reaching beyond the tympanic membrane. In some cases, the reflected signals (echoes) are characterized by different pattern: in a first pattern, only a single reflection is returned by the tympanic membrane, potentially indicating that no fluid exists behind the membrane. In a second pattern, two reflections occur, optionally with a time delay between them: a first reflection from the tympanic membrane, and a second reflection from one or more structures beyond the tympanic membrane, such as bones. In some cases, the second reflection is obtained only if a fluid medium is present intermediate the tympanic membrane and the bones.

In some embodiments, fluid (e.g. gel) is inserted into the ear to provide a fluid medium coupling between the ultrasound probe and the tympanic membrane. Additionally or alternatively, the probe itself comprises fluid or gel at its distal tip for providing a fluid medium coupling between the ultrasound element and the tympanic membrane.

An aspect of some embodiments relates to an integrated device for detection of middle ear content and/or condition. In some embodiments, the integrated device incorporates an RF module and a fluorescence module. In some embodiments, the RF module is used for preliminary detection of presence of fluid behind the tympanic membrane. Then, in some embodiments, lighting is applied (e.g. by one or more light sources) towards the tympanic membrane. Images of the tympanic membrane are then acquired by an imager, and a fluorescence spectra is optionally analyzed for detection of pathogens. A potential advantage of an integrated device may include performing initial screening using the RF module; then, only if fluid is present, the fluorescence spectra is collected. The described operation scheme may simplify usage, reduce the time required for diagnosing and optionally improve sensitivity.

In some embodiments, data collected and/or analyzed by the integrated device is presented to a user, for example on a display. In some embodiments, data includes an indication from the RF module as to whether or not fluid is present within the ear. In some embodiments, data includes an image of the tympanic membrane, optionally a colored image, obtained by the imager. In some embodiments, data includes a processed image of the tympanic membrane, for example having applied image processing algorithms, for example for facilitating detection of fluid, pathogens in the fluid, and/or other phenomena, such as bulging of the tympanic membrane. In some embodiments, data includes an estimation (for example, a probability) of existence of pathogens, and optionally classification of the types of pathogens. In some embodiments, data is presented using visual representations or models, such as graphs, tables, etc.

As referred to herein, a“device extension”,’’probe”, or“head” may refer to a distal portion of the device (such as a distal portion of an otoscope device) shaped and sized for insertion, at least in part, into an external ear canal. Optionally, the distal portion is tapering, for example, conical. Optionally, the distal portion is tubular.

As referred to herein, light arriving from the tympanic membrane may include light reflected, returned, and/or emitted by the tympanic membrane and/or its surroundings.

Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not necessarily limited in its application to the details of construction and the arrangement of the components and/or methods set forth in the following description and/or illustrated in the drawings and/or the Examples. The invention is capable of other embodiments or of being practiced or carried out in various ways.

Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not necessarily limited in its application to the details set forth in the following description or exemplified by the Examples. The invention is capable of other embodiments or of being practiced or carried out in various ways.

Exemplary diagnosis of middle ear content and/or condition

Referring now to the drawings, FIG. 1 is a flowchart of a general method for diagnosing a middle ear content and/or condition, according to some embodiments.

In some embodiments, examination of the ear is performed for patients suffering from ear-related symptoms and/or as a regular check-up examination. In some embodiments, a physician or other suitable health care provider screens the ear to search for illness, for example inflammation. In some embodiments, a non-invasive examination is performed, in which the internal ear canal and/or the tympanic membrane are viewed. In some cases, middle ear conditions are diagnosed based on characteristics of the tympanic membrane, for example as further discussed hereinbelow.

In some embodiments, a device configured for examination of the ear, such as an otoscope, is provided. In some embodiments, at least a portion of the device, for example a distal extension of the device is inserted at least in part into the external ear canal (101).

In some embodiments, the tympanic membrane is illuminated, while a plurality of spectral images are acquired (103). In some embodiments, the tympanic membrane is illuminated via a plurality of light sources, for example LEDs, directed towards the tympanic membrane. In some embodiments, different light sources are configured to emit light at different wavelengths. In some embodiments, different light sources are positioned to emit light at different directions or angles. In some embodiments, different light sources are operable independently. In an example, light is emitted from the different light sources sequentially, in a serial manner.

In some embodiments, a plurality of spectral images are acquired (103), for example using an imager of the device. In some embodiments, the imager comprises per pixel wide band pass filters. In an example, the imager comprises a TV-camera. In some embodiments, the imager comprises a matrix of CMOS sensors, each equipped with wide band pass filters, for example, RGB filters.

In some embodiments, the plurality of spectral images are analyzed (105). Optionally, machine learning methods are implemented to process the acquired images. In some embodiments, processing comprises obtaining a multi spectral image of the tympanic membrane. In some embodiments, processing comprises detecting wavelengths of the light emitted by (returning from) the tympanic membrane.

In some embodiments, according to the acquired images of the tympanic membrane, a middle ear diagnosis is provided (107). In some embodiments, diagnosis is provided based on one or more 2D images of the tympanic membrane. Additionally or alternatively, a 3D representation of the tympanic membrane is constructed and analyzed. In an example, the 3D representation is constructed by lighting the tympanic membrane from multiple directions, for example from at least 4 directions, and observing for shadowed and/or lighted areas in the obtained images.

In some embodiments, characteristics of the tympanic membrane such as color, translucency level, bulging of the membrane and/or other shape deformations are searched for. In some embodiments, a level of middle ear fluid and optionally its viscosity are searched for. In some embodiments, visibility of the malleus bone is searched for. In some embodiments, a presence and optionally amount of cerumen (ear wax) is searched for. In some embodiments, findings are associated with a specific condition. Various conditions that may be determined by analyzing the acquired images may include: inflammation (acute otitis media (AOM) and/or otitis media with effusion (OME), cholesteatoma, perforation or rupture of the tympanic membrane, and/or other conditions (see also FIG. 5).

In some embodiments, examination of the ear, for example from initial positioning of the device in the ear canal to obtaining at least one image of the tympanic membrane and optionally indicating significant findings within the image is performed within a time period of less than 10 minutes, less than 5 minutes, less than 2 minutes, less than 30 seconds or intermediate, longer or shorter time periods. Optionally, the diagnosis is provided immediately following examination. In some embodiments, examination is carried out in a similar manner to standard ear examination using an otoscope.

FIG. 2 is a flowchart of a method for diagnosing a middle ear content and/or condition based on spectral images of the tympanic membrane and/or of middle ear fluid behind the tympanic membrane, according to some embodiments. In some embodiments, fluorescence spectra arriving from the tympanic membrane (emitted by the tympanic membrane) is measured.

In some embodiments, light is emitted towards the tympanic membrane from a plurality of light sources (201). Optionally, light is emitted sequentially, such that each of the light sources is activated independently in a serial manner. Alternatively, light is emitted simultaneously from two or more of the light sources.

In some embodiments, the plurality of light sources are activated such that each light source emits light at a different wavelength. Optionally, the excitation (illumination) wavelength is selected from between 200 nm-1000 nm. Optionally, the light sources are activated sequentially. In an example of a lighting pattern, the first light source (e.g. a LED) emits at 250- 280 nm, the second light source emits at 405-450 nm, and so forth. In some embodiments, near- infrared and/or infrared ranges may be used, including wavelengths of between 780 nm to 2500 nm, 700 nm- 1000 nm, or intermediate, higher or lower ranges. Optionally, near infra-red or infra-red wavelengths are emitted in combination with visible light spectra, for example: NIR(810nm 750-950 nm), IR(940nm 750-1000nm), Red(660nm 620-750nm), white(390-700 nm).

In some embodiments, wavelengths at emission are selected according to expected emission spectra of certain pathogens. Optionally, by knowing an expected fluorescence fingerprint of each of a plurality of pathogens (for example 1, 2, 3, 4, 6, 8, 10 different pathogens), the illumination wavelengths can be selected to increase a likelihood of detecting the pathogen fingerprints, in cases in which pathogens, such as bacteria, are present. In some embodiments, spectrographs are generated for various pathogens. Optionally, using optimization methods, illumination wavelengths that best distinguish between different bacteria are identified. In some embodiments, the device is pre-programmed with different illumination wavelength sets that can be implemented for detecting specific pathogens.

In some embodiments, following illumination by each of the light sources, a fluorescence spectra of the tympanic membrane is detected, optionally via an imager equipped with per pixel wide bandpass filters (203). In some embodiments, the filters comprise RGB color filters. Optionally, a color filter array in the form of a Bayer filter mosaic is used. In some embodiments, RGB-IR (infrared) filtering may be applied at image detection.

In some embodiments, the process of illuminating the tympanic membrane and capturing light arriving from the tympanic membrane in response to the illumination is repeated (205). Optionally, the process is repeated until a sufficient number of spectral images are acquired for generating a 2D image of the tympanic membrane (207).

In some embodiments, the 2D image is analyzed for detection of one or more of: pathologies of the middle ear, a specific anatomy of the middle ear, general content of the middle ear (including, for example, tympanic membrane characteristics such as color, translucency level, rupturing if exists, existence of visible patterns or shapes, and/or other characteristics. In some embodiments, the 2D image is analyzed for detection of fluoroscopic fingerprints of pathogens (209). Based on in-vitro evidence (see for example Spector, Brian C., Lou Reinisch, Dana Smith, and Jay A. Werkhaven. "Noninvasive fluorescent identification of bacteria causing acute otitis media in a chinchilla model." The Laryngoscope 110, no. 7 (2000): 1119-1123 ) that different pathogens are characterized by different fluoroscopic fingerprints, it may be possible to detect existence of pathogens and optionally differentiate between different types of pathogens such as H. Influenzae, S. pneumoniae, S. aureus, M. catarrhalls according to their fingerprints. In some embodiments, pathogen existence is indicative of inflammation (acute otitis media (AOM) and/or otitis media with effusion (OME).

Optionally, a 3D model of the tympanic membrane is constructed (211). In some embodiments, a plurality of 2D images are analyzed for generating a 3D model from which a topography of the tympanic membrane can be assessed. In some embodiments, one or more bulges and/or depressions of the tympanic membrane are detected from the 3D model (213). Such bulging may be indicative, for example, of acute otitis media.

It is noted that additionally or alternatively to optical imaging using broad bandpass filters for example as described herein, other modalities may be used, such as ultrasound and/or RF. In some embodiments, existence of middle ear fluid is detected using ultrasound. Optionally, a level of fluid and/or a viscosity of the fluid (thin/thick fluid) are assessed, due to their effect on attenuation of ultrasound. In some embodiments, use of ultrasound requires using a liquid medium to enable transfer of the ultrasound signals, therefore liquid (e.g. saline) may be injected into the ear canal and/or a liquid sac may be placed in front of the examining device.

Exemplary system for diagnosing a middle ear content and/or condition

FIGs. 3A-B are a schematic drawing of a system for diagnosing a middle ear content and/or condition (3A), and a schematic drawing of the path of light through the system (3B), according to some embodiments.

In some embodiments, a device 301 for ear examination comprises a conical body 303.

In some embodiments, body 303 is comprised of a solid material, such as clear medical grade plastic, for example polycarbonate. In some embodiments, the solid material forming the cone allows for light to pass through without causing scattering of the light. In some embodiments, the solid material transmits the emitted light such that less than 10%, less than 5%, less than 2% or intermediate, higher or smaller percentage of the emitted light is scattered, reflected and/or absorbed by the solid material of the cone. Optionally, the solid material is transparent.

In some embodiments, device 301 comprises a plurality of light sources 305, such as 2, 4, 6, 8, 10, 12, 16 light sources or an intermediate, larger or smaller number of light sources. In some embodiments, light sources 305 are mounted at a proximal head portion 307 at the wide end of the cone body 303. In some embodiments, as shown for example in the cross sectional view along a wide axis 307 of cone body 303, the light sources are peripherally arranged around the circular head. Optionally, the light sources are distributed such that a central angle a of between 20-60 degrees, such as 30 degrees, 45 degrees, 55 degrees or intermediate, larger or smaller angle separates between adjacent light sources. Optionally, separation angle a is selected according to the number of light sources being used. In some embodiments, each of the light sources is activated to emit light at a distinct wavelength.

In some embodiments, the number of light sources and/or a spatial arrangement of the light sources are selected so that all portions of the tympanic membrane (schematically illustrated at 331) will be illuminated, optionally uniformly. In an example, the tympanic membrane is divided into 4 quadrants, and 4 LEDs are used for illuminating the 4 quadrants. Optionally, when all 4 LEDs are activated, the tympanic membrane is lighted substantially uniformly. (In a similar manner- the tympanic membrane may be divided into a different number of segments, and a corresponding amount of LEDs used for lighting it. For example, 3 segments illuminated by 3 LEDs, 5 segments illuminated by 5 LEDs, etc). In some embodiments, a number and/or arrangement of light sources is selected to be sufficient to illuminate the tympanic membrane from a plurality of directions. A potential advantage of illuminating the membrane from multiple directions is producing lit areas as well shaded areas. Optionally, light/shade differences may be used as basis for determining a shape and/or structural characteristics of the tympanic membrane, such as bulging of the membrane.

Other light sources may be used, for example: lasers, intense pulsed light (IPL), flashlamps, and discharge lamps.

In some embodiments, an axial lumen 311 extends throughout the cone body 303, from the proximal end to the distal end of the body. In some embodiments, a distal extension 315 extends from a distal (tapered) end of the cone body. Optionally, the distal extension or at least a portion of it is shaped and sized to fit within the external ear canal. Optionally, extension 315 is positioned within the ear such that a distal end 319 of the extension is located adjacent the tympanic membrane. Optionally, distal end 319 of the extension is positioned at a distance of between 1-5 mm, 3-10 mm, 1-3 mm or intermediate, longer or shorter distances from the tympanic membrane. In some embodiments, extension 315 comprises a sensor, for example a pressure sensor, for determining a location of the extension relative to the tympanic membrane. In some embodiments, the sensor is a pressure gauge inserted between the distal end of the extension and the tympanic membrane. Optionally, by approximating the distal end towards the tympanic membrane, the pressure level rises.

In some embodiments, the extension is substantially cylindrical. Optionally, the extension is axially aligned with the lumen 311. In some embodiments, a diameter 333 of cylindrical extension 315 is small enough so that at least a portion of the extension can be easily introduced into the external ear canal. Optionally, diameter 333 ranges between 1-5 mm, 2-4 mm, 3-6 mm or intermediate, larger or smaller diameters.

In some embodiments, an imager 313 is positioned within extension 315 and/or within lumen 311, at a location suitable to capture light arriving from the tympanic membrane. Optionally, imager 313 comprises a standard TV camera. In some embodiments, imager 313 comprises a CMOS sensor matrix, and/or a CCD sensor matrix. Each of the sensors of the matrix includes one or more wide bandpass filters. In an example, each sensor includes RGB (red-green- blue) colors filters. In some embodiments, imager 313 captures spectral images of the tympanic membrane in response to illumination of the tympanic membrane by the plurality of light sources. Optionally, images are captured during a time period of between, for example, 30 seconds to 3 minutes, 10 seconds to 1 minute, 1-3 minutes or intermediate, longer or shorter time periods. In some embodiments, a number of acquired images is associated with the number of light sources being used, optionally being equal to the number of light sources being used. In some embodiments, even a single image is enough for detecting a spectra which is indicative of pathogen presence.

Optionally, imager 313 is synched with the rate of light emission so that capturing is coincident with the excitation by each of the light sources.

In some embodiments, during operation, light emitted by one or more of the light sources travels distally through the solid material portions of the cone body, optionally into axial lumen 311 and then around imager 313. In some embodiments, light passes in a ring-shaped pattern around the imager.

In some embodiments, device 301 includes optical components, such as lenses, diffusers, beam collimators and/or other optical components.

In some embodiments, since the emitted light is transmitted directly through the solid (optionally transparent) material forming the cone body, a diffuser may not be needed.

In some embodiments, device 301 comprises a handle 321 for manipulation by a user, such as a physician. Optionally, handle 321 extends proximally from the proximal end of the cone body.

In some embodiments, device 301 comprises or is in communication with a processor 323. In some embodiments, processor 323 is configured for analyzing the spectral images acquired by the imager. Optionally, processor 323 is configured for storing the images. In some embodiments, processor 323 comprises a communication module 325. Communication module may be configured for sending and/or receiving data to or from one or more of: an external memory, cloud storage, clinical database, cellular phone, and/or others. In some embodiments, communication module 325 connects to a dedicated cell phone application, suitable for analyzing and/or storing and/or displaying the acquired images and/or diagnosis.

In some embodiments, device 301 comprises or is in communication with a color screen display 327. In some embodiments, screen display 327 is located on handle 321. Optionally, images and/or analysis results and/or recommendations (e.g. guidance for improving a positioning of the device when in the ear) are presented on the screen. In some embodiments, an image displayed to the user (e.g. physician) includes added markings to indicate significant elements in the image, for example- locations of bacterial growth, discoloring of the tympanic membrane, a rupture in the tympanic membrane and/or other significant elements which may assist in diagnosing the ear content and/or condition. In some embodiments, device 301 is compact enough so that it can be held and/or operated single handedly by the user. In some embodiments, a total length 329 of cone shaped body and the extension, as measured for example from the proximal wide end of the cone shaped body to the distal end of the extension, is short enough to be suitable for manipulation by a user’s hand.

In FIG. 3B, an example of the path of light through device 301 is shown. In some embodiments, light 341 rays travel from a proximal end of cone body 303 in a distal direction. In some embodiments, the light passes through the walls of the cone body, travelling around imager 313 such that it forms a ring shaped pattern.

Exemplary acquiring and analyzing of tympanic membrane images

FIG. 4 is a schematic diagram of the process of acquiring and analyzing images of the tympanic membrane, according to some embodiments.

In some embodiments,“N” independent light sources (401) are activated to emit light towards the tympanic membrane. For each of the“N” light sources, light arriving from the tympanic membrane following emission is captured by a sensor matrix of the imager in which each sensor comprises“K” different wide band pass filters (403). In an example, each sensor comprises RGB filters, for generating 3 spectral combinations of the light arriving from the tympanic membrane.

In some embodiments, the process of emitting light and capturing spectral images of the tympanic membrane is repeated. Optionally, the process is repeated until the tympanic membrane had been illuminated by all independent light sources. In some embodiments, the captured images are recorded and stored (for example in a device memory). In some embodiments, a 2D image of the tympanic membrane is generated (405). Optionally, each pixel of the generated image is calculated as a combination of“N”*”K” spectral images that were captured.

In some embodiments an RGB image of the tympanic membrane is generated based on the collected data and displayed to the user (e.g. a physician) (407). In some embodiments, additional processing is performed to determine the original wavelengths of the light arriving from the tympanic membrane (409). Optionally, if the calculated original wavelengths do not fit within expected ranges (such as expected ranges in accordance with RGB intensity profiles), the calculated wavelengths are filtered as noise. A potential advantage of filtering based on expected wavelengths ranges may include improving a signal to noise ratio, allowing image detection of higher sensitivity. In some embodiments, the following thumb rule is implemented: the expected returning wavelength/ illumination wavelength = a number between 1 and 2. FIG. 5 is a schematic drawing of the human ear. In some embodiments, a distal device extension 501 is advanced within the external ear canal 503, until being positioned in proximity to the tympanic membrane 505.

In some embodiments, movement of the device (for example due to hand fluctuations) is compensated for by using a high resolution imager and/or a high frame rate.

Additionally or alternatively, a mechanism for holding the device in a fixed position relative to the tympanic membrane is used, for example, an air filled balloon which positions the device extension against the walls of the external ear canal.

In some embodiments, characteristics of the tympanic membrane 505 such as a structure, translucency level, color, smoothness, and/or others are examined. In some embodiments, existence and/or a level of and/or a viscosity of inner ear fluid 507 is examined. In some embodiments, a condition of the ossicles 509 is examined.

In some embodiments, the following conditions are tested for using devices and/or method for example as described herein: Tympanosclerosis, Perforation of the tympanic membrane, Acute otitis externa, Serous otitis media, Exostosis Atrophic otitis media, Keratosis Obturans, Red reflex, Otomycosis, cholesteatoma.

In the example of cholesteatoma, when using an imager with RGB filters, a spectra which is indicative of this condition may be detected by the filters, for example by the green filter (G), as it is characterized by wavelengths detectable by the filters, for example between 405 nm and 450 nm.

FIGs. 6A-B are a flowchart of a method for indicating existence of pathogens in the ear using RGB based detection (figure 6A) and a schematic graphic representation of RGB wavelength sensitivity (figure 6B), according to some embodiments.

In some embodiments, light is emitted towards the tympanic membrane at wavelengths which are not detectable by RGB filters (601). In some embodiments, light is emitted sequentially by a plurality of light sources which are independently controlled.

In some embodiments, light arriving from the tympanic membrane in response to illumination is captured via an imager equipped with RGB filters (603). Based on that in some cases the spectra of certain pathogens falls within wavelength ranges which are detectable by the RGB filters, detection itself is, in some embodiments, an indication for the presence of these pathogens. (605).

In an example, the spectra of enzymes and/or coenzymes and/or amino acids and/or other proteins of certain pathogens (such as H Influenza, M Cataralis, S Pneumoniae, S Aureas or any combination thereof) is characterized by wavelengths higher than a minimal wavelength detected by the RGB filters, for example, higher than 375 nm which is the shortest wavelength detectable by the blue filter. The ability to detect such spectra is indicative, in some embodiments, of the presence of one or more of these pathogens. In an example, existence of amino acids such as Tryptophan, Tyrosine and/or Phenyloalanine affects the spectra such that it is characterized by wavelengths which are detected by one or more of the RGB filters. In some embodiments, by detecting one or more amino acids, the presence of bacteria is indicated. In a specific example, only tryptophan is detected, characterized by a wavelength range of between 230-350 nm. Optionally, the emittance of Tryptophan is detected by the blue or green filters. In some embodiments, for the purpose of identifying Tryptophan, one or more of the light sources are excited to emit light at wavelengths shorter than, for example, 350 nm.

Optionally, a pathogen type is indicated based on the spectra. In some embodiments, the system for example as described herein above (for example, the system processor) is programmed with known pathogen fingerprints (an expected fluorescence spectra of one or more pathogens) and upon detection of a similar or like spectra by the imager, an indication regarding the presence of the one or more pathogens is provided. In some embodiments, the processor is configured to compare a current spectra (for example, the wavelength ranges obtained) to a database and/or table of known expected wavelength ranges correlated with the presence of pathogens.

In some embodiments, the user (e.g. physician) is acknowledged about the presence of pathogens by an alert, for example a screen displayed message, a light indication, a sound indication, and/or other; additionally or alternatively, the acquired image is displayed to the user along with markings showing a location and/or distribution of pathogens behind the tympanic membrane.

In some embodiments, one or more specific types of pathogens are recognized and indicated (607), for example by comparing to known fluorescent fingerprints associated with each pathogen. Optionally, one or more thresholds are set (for example to wavelength values) to determine whether a currently obtained spectra is sufficiently correlated with a known pathogen fingerprint.

FIG. 6B is a schematic graphic representation of RGB wavelength sensitivity, in accordance with some embodiments.

In some embodiments, each pixel-sensor of the imager includes RGB filters. In an example, each of the RGB filters passes a selected wavelength range, for example: the blue filter passes wavelengths between“A” and“B, the green filter passes wavelengths between“C” and “D”; and the red filter passes wavelengths between“E” and“F”. In some embodiments, the illumination wavelengths are selected from within ranges that are not passed by the filters (e.g. wavelengths that are shorter than“A” and/or wavelengths that are longer than“F”), so that detection is“blind” to the illumination wavelengths.

In some embodiments, if the fluorescence spectra arriving from the tympanic membrane is within the wavelength ranges detectable by the RGB filters, pathogen presence may be indicated. Optionally, spectra of a specific pathogen is characterized by a specific set of RGB wavelength values.

FIGs. 7A-B are examples of images displayed to a user, separately or in combination, according to some embodiments.

The image of 7A shows a distribution of bacteria one or both of the tympanic membrane and behind the tympanic membrane, e.g. in the ear fluid. The images of 7B show three tympanic membrane conditions: a normal tympanic membrane 701; a tympanic membrane in which bulging and erythematous are exhibited 703; and a tympanic membrane in which otitis media with effusion is exhibited 705.

In some embodiments, an image for example as shown in 7A is overlaid on the tympanic membrane image, for example as shown in figure 7B. Optionally, markings are made onto the combined image to indicate pathogen characteristics such as: the pathogen type(s); distribution 707; size of colony and/or other.

In some embodiments, markings are made to point out conditions such as rupture of the tympanic membrane, discoloring of the membrane.

In some embodiments, combining and marking of the image is carried out by designated software.

Exemplary radio-frequency mechanism for detection of a middle ear condition

FIGs. 8A-E schematically illustrates a device comprising a radio-frequency mechanism for detection of middle ear effusion, according to some embodiments.

In some embodiments, the RF mechanism is configured for detection of fluid behind the tympanic membrane, by measuring an effect on the electric field and/or magnetic field, such as: absorbance of electromagnetic waves, phase polarization, reflection, impedance, and/or other effects or phenomena associated with electrical conduction.

In some embodiments, cylindrical extension 801 comprises a set of RF coils 803, coaxially aligned, and separated by a diamagnetic insert 805, for example an aluminum insert. In some embodiments, an insulating core 807, for example formed of plastic, extends axially throughout a center of the cylindrical extension. The described construction is schematically illustrated at a cross section in figure 8D, and photographed in figure 8C. In some embodiments, the coils are electrically connected to each other via an AC measurement bridge scheme, as shown for example in FIG. 8F.

In some embodiments, during use, cylindrical extension 801 is introduced into the patient’s ear canal, and advanced such that its distal end is in proximity to the tympanic membrane. Optionally, the cylindrical extension is advanced as close as possible to the tympanic membrane. Then, in some embodiments, an electrical current is passed through the coils (supplied by a power source), and a resulting magnetic field is detected. In a situation in which fluid is present behind the tympanic membrane, different voltage values will be measured for each of the coils, changing the magnetic field (as schematically shown in FIG. 8E2). If no fluid is present, a similar voltage will be measured (as schematically shown in FIG. 8E1).

Alternatively, even if no fluid exists, some voltage difference (e.g. below a threshold) may be measured.

In some embodiments, the power source is configured to generate a square wave signal, at a selected frequency (in an example, 7MHz).

The schematics of measurement are demonstrated by the circuitry of FIG. 8F, according to some embodiments. In some embodiments, a current source is connected to port 1. Potentiometers R1 and R2 are calibrated such that in the absence of middle ear fluid, a voltage difference between point 3 and point 4 does not exist (equals to zero). In the case of middle ear effusion, the voltage difference between point 3 and point 4 will be different than zero. In some embodiments, the voltage difference is amplified and optionally filtered, and the resulting signal is digitized.

An exemplary construction may include the following: each of the two RF coils may comprise of an insulated copper wire, optionally rotated 160 turns, and having a diameter of 0.15 mm; a length 809 (thickness) of each coil (as measured along the long axis of the cylindrical extension, see FIG. 8D) may range between 1.5-3 mm, such as 2.40 mm, 2 mm, 3 mm or intermediate, longer or shorter length; a length 811 (thickness) of the diamagnetic insert (as measured along the long axis of the cylindrical extension, see FIG. 8D) may range between 0.5-2 mm, for example 0.7 mm, 1 mm, 1.5 mm or intermediate, longer or shorter length; a total length 813 of the cylindrical extension (see FIG. 8D) may range, for example, between 6-9 mm, such as 6.5 mm, 7.2 mm, 8.5 mm or intermediate, longer or shorter length; an external diameter 815 of the cylindrical extension may range between 2.5-4 mm, such as 3 mm, 3.5 mm, 3. 9 mm or intermediate, longer or shorter diameter; an internal diameter 817 of the cylindrical extension may range between 2-3.5 mm, such as 2 mm, 2.5 mm, 3.2 mm or intermediate, longer or shorter diameter.

In an example corresponding with the above exemplary construction, the electrical current is in the form of a square wave, at a frequency of 7MHz and an amplitude of about 100mA; and the resulting voltage difference (if detected) is band-pass filtered at a frequency of 7MHz, and digitized at a frequency of at least 15MHz (optionally according to the Nyquist frequency).

In some embodiments, an effect on the electric and/or magnetic field is detected and/or measured using an antenna, such as a printed antenna. In some embodiments, a near field behavior of the electromagnetic field (close to the antenna) is detected and measured.

In some embodiments, reference is made to a look-up table (e.g. a table stored on the device controller memory and/or on a remote server) which correlates between a detected and/or measured change in a property (e.g. voltage, waveform, frequency) and a physical condition associated with that property, such as existence of inner ear fluid, rupturing of the tympanic membrane, and/or other conditions. Optionally, the look-table links between various applied waveforms and an expected measured waveform.

FIG.8G is a flowchart of a method for detecting presence of fluid behind the tympanic membrane using a radio-frequency mechanism, according to some embodiments.

At 851, in accordance with some embodiments, a device probe comprising two or more conductive coils is introduced into the ear canal. In some embodiments, the coils are arranged with a space therebetween. Optionally, a diamagnetic insert or ring is positioned intermediate the coils, for example as further described herein.

In some embodiments, the coil includes a wound wire or a printed wire.

At 853, in accordance with some embodiments, electrical current is conducted through the coils. Optionally, an alternating current is applied.

At 855, in accordance with some embodiments, the electromagnetic field and/or differences in the electromagnetic field are measured. In some embodiments, a voltage difference which develops between two opposite ends of each of the coils is a function of the electrical impedance of the coil. In some embodiments, when fluid is present in the ear, approximation of the RF probe to the tympanic membrane results in changes to the measured electromagnetic field, as a result of the differences in impedances. In some embodiments, a calibration measurement is performed for measuring the electromagnetic field when the probe is a distance away from the tympanic membrane. Then, a measurement of the electromagnetic field performed in proximity (e.g. adjacent) the tympanic membrane is compared to the calibration measurement to detect presence of fluid. Additionally or alternatively, in some embodiments, measurements (e.g. of voltage, electromagnetic field and/or other parameters) of a coil positioned at a proximal position are used as reference or baseline for measurements obtained from a coil positioned at a more distal position, closer to the tympanic membrane (and thereby potentially closer to any fluid, if present, behind the membrane).

In some embodiments, the two coils are positioned with a space between them (e.g. axial space) which, on the one hand, is large enough to reduce or prevent a mutual effect on the electromagnetic field of each of the coils; and, on the other hand, is short enough to maintain a total length of the probe as small as possible to facilitate its insertion, at least in part, into the external ear canal).

Exemplary experiment setup and results for different device probes

FIGs. 9A-17C describe an experiment setup and results in which device probes constructed according to three different techniques were tested using an artificial model of the human ear. The probes included an ultrasound based probe, a light based probe, and a radio frequency probe. Data obtained by each of the probes was analyzed and processed using designated software. The different probes were tested for the ability to detect presence of fluid behind the tympanic membrane and for the ability to identify the type of fluid and/or viscosity of the fluid based on the data acquired by the probe. The different probes were further assessed for determining ease of use and cost aspects.

It is noted that in some embodiments, two or all three techniques (and/or additional techniques) may be implemented in the same single otoscope device.

It is noted that dimensions, sizes, and/or constructions used in this experiment are to be referred to only as non-limiting examples.

FIGs. 9A-C are images of different views of a 3D-printed model of the human ear 901 used in an experiment performed in accordance with some embodiments. Colon tissue obtained from swine was used in the model for imitating the tympanic membrane (the tissue is not observable in the image, as it was inserted into the model). A hydraulic system 903 was used for injection of various types of fluids into a space located behind the swine tissue. Calibration and initial testing were performed using an NaCl physiologic solution, and other fluids used in the experiment included water, salted water, gelatin, and animal blood. The hydraulic system provided for gradually injecting the fluid to the space behind the swine tissue. The fluid was injected gradually until reaching about a half of the total available volume of the space behind the swine tissue. The total volume of available space was 3 ml, and the fluid injected for each of the readings was at a volume of 0.5ml. FIGs. 10A-C are images of the three device probes tested, arranged on a platform constructed for an experiment performed in accordance with some embodiments. The images show an RF based probe 1001; an ultrasound based probe 1003; and a light based probe 1005.

FIGs. 11A-B show an example of circuitry connecting between the RF and ultrasound modules (11A) and an example of a digital acquisition assembly (11B) for transferring and/or processing of data obtained by the device probe, in accordance with some embodiments.

In FIG. 11A, the RF device probe 1101 and the ultrasound device probe 1103 are connected via switch circuitry 1105 to a digital acquisition assembly 1107. The digital acquisition assembly is directly connected or is in communication with a computer 1109 (in the experiment, a USB type connection was used). Other connections may include wireless connections such as Bluetooth, wi-fi, etc. In some embodiments, data may be transferred to a remote server. Optionally, data collected from a plurality of measurements and/or from a plurality of patients is stored and/or analyzed by a remote server.

In FIG. 11B, details of an exemplary digital acquisition assembly 1107 are shown. In some embodiments, the digital acquisition assembly includes an analog to digital converter (ADC), optionally high-speed; a configurable chip such as a field programmable gate array chip (FPGA); a microprocessor control unit (MCU) and an interface for connecting with the computer 1109 on which the proprietary software is installed. In the experiment performed by the inventors, a designated software program was used for processing and analyzing data obtained by the three different probe types.

Ultrasound based device probe

FIGs. 12A-D show structural and functional details of an ultrasound device probe, according to some embodiments. In some embodiments, the ultrasound probe comprises a piezoelectric transducer suitable for emitting and/or receiving signals. In some embodiments, as was performed in this experiment, the piezoelectric transducer was used for both emitting of ultrasound signals and for receiving returning echoes. Additionally or alternatively, in some embodiments, signals may be emitted or received by different piezoelectric transducers.

In some embodiments, analysis of the echoes is performed to assess a location from which the signal was reflected. In some embodiments, as performed in this experiment, analysis of the echoes is configured to indicate presence of fluid behind the tympanic membrane. Optionally, an amount and/or volume of fluid are detected or estimated based on the returning echoes. In some embodiments, as performed in this experiment, analysis of the echoes, for example, assessment of a time delay or difference between the emitted signal and the returning echo is correlated with a viscosity of the fluid. Optionally, the

FIGs. 12A-B show an example of an ultrasound probe constructed for use in the experiment. FIGs. 12C and 12D show exemplary parameters used in the experiment, including, for example:

Transducer frequency of ~ 41.8 KHz; (exemplary range lOKHz-lOOKHz)

Number of excitation pulses applied: 4 (exemplary range: 1-15)

Echo sampling frequency: 510 KHz (exemplary range: 100 KHz-2500 KHz)

Echo sampling delay: 151 psec (exemplary range: 0-500 psec)

FIGs. 13A-B show examples of echo signals recorded by a digital scope when no fluid was injected in the model (FIG. 13A) and when fluid was present (FIG. 13B), in the experiment performed according to some embodiments. In some embodiments, as can be observed from the experiment results, the presence of fluid caused a change in the echo signal amplitude(s).

FIG. 13C shows an exemplary screen of a user interface, showing the recorded echo signal and a Fourier transformation of the signal performed in accordance with some embodiments.

Light based device probe

FIGs. 14A-E show structural and functional details of a light based device probe, according to some embodiments.

In some embodiments, as shown for example in the images of FIGs. 14A-D, the light based device probe 1400 comprises a light guiding cone 1402; one or more light sources 1404, and a light conductor (not shown) optionally extending through the cone.

In some embodiments, the light guiding cone is sealed to prevent surrounding light from entering and/or to prevent from light from exiting the cone radially outwards. In some embodiments, the light guiding cone is shaped to converge the emitted light towards a selected area or location, such as towards the tympanic membrane. In some embodiments, as was used in the experiment, the light guiding cone comprises a black coating on the inside. In some embodiments, a reflective coating is applied onto an inner wall of the cone.

In some embodiments, the light conductor comprises a tube or channel which extends along the light guiding cone. Optionally, the light conductor is formed of a semi-transparent material, for example a plastic, for example polycarbonate. In some embodiments, as was used in the experiment, the probe was connected to a digital microscope 1406 used for capturing the images. In some embodiments, a live streaming of the field of view is obtained.

The table of FIG. 14E lists details of the components used in the experiment. For example, a digital microscope having a sensor resolution of 5 mega pixel and a lens of 13 inch FOV was used. FIGs. 15A is an image of the device and the user interface screen as used in the experiment performed in accordance with some embodiments. FIGs. 15B-C show examples of the images captured by the light based device, where in FIG. 15A there was no fluid in the model, and in FIG. 15B fluid was injected in the model, filling about a half of the available space behind the tissue portion.

In some embodiments, color analysis of the acquired images is indicative of the type and/or amount of fluid behind the membrane. In some embodiments, as was performed in the experiment, a color analysis is performed by comparing two or more selected points on the image. Optionally, one point is used as a reference or baseline for the other point.

In some embodiments, a color analysis of the images is presented (e.g. to a user, such as a physician) using an RGB representation model and/or using an HSV (hue, saturation, value) representation model. In some embodiments, values of the actual images are normalized according to these models and/or others for analysis purposes.

In some embodiments, a transparency level of the tympanic membrane is estimated or calculated from the acquired images.

In some embodiments, image processing algorithms (such as described hereinabove) are applied for detection of 3-dimenional phenomena such as bulging of the tympanic membrane.

Radio-frequency based device probe

FIGs. 16A-D show structural and functional details of a radio-frequency based device probe, according to some embodiments. In some embodiments, as shown in FIG. 16A and in the cross section of FIG. 16B, the RF probe comprises two coils 1601, 1603 separated by a diamagnetic insert 1605. In some embodiments, the coils are wrapped around a core 1607, for example formed as a tube.

In some embodiments, the coils and the diamagnetic insert are arranged along the similar long axis. In some embodiments, the coils are co-axial.

In some embodiments, the coils are formed of a wounded wire, such as a copper wire.

In some embodiments, the diamagnetic insert is formed of aluminum.

In some embodiments, the core is formed of a plastic tube. In some embodiments, a diameter of each of the coils and of the insert is small enough to fit within a diameter of the external ear canal.

Exemplary dimensions and construction include:

Each coil having a wire diameter of 0.15mm, 160 turns of the wire, and a thickness (e.g. as measured along the long axis of the core) of 4.5 mm; an inner diameter of the core is, for example, 5 mm; an outer diameter of the core is, for example, 8 mm; a thickness of the diamagnetic insert positioned in between the coils is, for example, 1 mm.

In another example, each coil comprises 100 turns of the wire and a thickness of 2 mm; optionally used with a ring shaped aluminum diamagnetic insert having a thickness of 0.6mm.

In another example, each coil has a wire diameter of between 0.15-0.2 mm; between 10- 15 turns of the wire; an inner diameter of between 1.4- 1.8mm. In this example, a diamagnetic insert may have a thickness of, for example, 0.3-0.8mm.

In some embodiments, the coil inductance is between 3mH- 10 pH. In some embodiments, the working frequency is between 2MHz-12MHz.

FIG. 16C shows an example of an RF probe constructed for use in the experiment. In some embodiments, the coils are powered by an AC source.

FIG. 16D shows examples of operation parameters for the RF probe, including for example:

A sampling rate of 25000 KHz (exemplary range: 100-25000 KHz).

A probe excitation frequency of 7025 KHZ (exemplary range: 10 KHz-12500 KHz).

FIG. 17A shows one of the experiment setups for testing the RF probe, in accordance with some embodiments. In some embodiments, it is expected that the recorded signal will change based on the absorbance of electromagnetic waves within body fluid, e.g. within fluid behind the tympanic membrane. Therefore, in the experiment setup, the probe was tested in two conditions: when held in the air (imitating insertion into a human air having no fluid behind the tympanic membrane, and under the assumption that within the ear itself the probe will be surrounded mostly by air and/or optionally ear wax). In the second tested condition, the probe was held in proximity to fluid, using a 0.5cm ^A 3 volume of fluid. In both conditions, differences in the electromagnetic field were recorded and viewed using an oscilloscope: FIG. 17B is an image of a recording obtained when the probe was held in the air and FIG. 17C is an image of a recording obtained when the probe was held in proximity to the fluid.

The results of measurement are presented by the graph of FIG. 17D- as can be observed, the signal intensity rises as the probe is moved closer to the fluid (i.e. closer to the tympanic membrane, behind which the fluid is located). When the probe is located a distance away from the fluid, such as at a distance of 4 mm and longer, the signal is low and remains relatively constant. In some embodiments, even a single measurement (including, for example, conducting of current to the coils and measurement of voltage differences between the two coils) may be sufficient to provide an indication of existence of fluid. In an example, the measurement takes less than 5 seconds, less than 3 seconds, less than 2 seconds or intermediate, longer or shorter duration.

The experiment results may indicate that in some embodiments, by positioning the RF probe at a distance of 4 mm or less, 5 mm or less, 7 mm or less, or intermediate, longer or shorter distances from the tympanic membrane, the received signal may be indicative of presence of fluid behind the membrane. Optionally, a distance for positioning the probe is selected taking into account the sensitivity of the probe, the operation frequency, and/or other parameters. Optionally, the signal intensity changes in response to the location of the probe relative to the fluid.

In some embodiments, the probe itself may include fluid at an amount and/or arrangement which produces a desired baseline electromagnetic field, such as for calibration purposes.

Integrated device probe

In some embodiments, different modules and/or technologies are implemented in the same device. For example, an otoscope device may include: an RF module and an ultrasound module, an RF module and light based module, a light based module and an ultrasound module. Optionally, all three modules are implemented in the same device.

In some embodiments, the device circuitry is configured for independent control of each of the modules. Optionally, one or more switches provide for automatic and/or user instructed selection of a module. Optionally, modules are actuated simultaneously or consecutively.

In some embodiments, a module is selected for use according to type of parameter to be detected and/or estimated. For example, for detection of presence of fluid, an RF module may be most advantageous; for detection of fluid type, a light based module may be most advantageous; for detection of fluid viscosity, an ultrasound module may be most advantageous.

FIG. 18 is a block diagram of an integrated device, according to some embodiments. In some embodiments, device 1800 comprises an RF module 1802, for example as describe herein; one or more light sources 1804, positioned and configured for emitting light towards the tympanic membrane; an imager 1806 configured for capturing light returning from the tympanic membrane; and optionally one or more filters 1808, such as an RGB filter. In some embodiments, the device comprises powering means 1810, for example, a battery. In some embodiments, the device comprises control circuitry 1812 for activating the device modules and components. In some embodiments, the device comprises or is in communication with a user interface 1814, optionally including a display. In some embodiments, the user interface is configured on a computer, tablet computer, cellular phone (optionally using a designated cell phone application) and/or other suitable means.

In an exemplary method of using the integrated device, the RF module is activated first, to detect if fluid is at all present behind the tympanic membrane. Then, in some embodiments, optionally only if fluid exists, the one or more light sources are activated to illuminate the tympanic membrane. In some embodiments, the imager is activated to capture one or more images of the illuminated membrane. Optionally, imaging is performed via one or more filters, such as an RGB filter. Optionally, the filter is positioned in the imager itself.

In some embodiments, the captured images are analyzed, for example as described hereinabove. Optionally, a fluorescence spectra of the tympanic membrane is detected and analyzed for the presence of pathogens, such as bacteria.

Exemplary probe structures

FIGs. 19-21 show exemplary structures (shown at a cross-section) of a device probe, including a light-based probe (FIG. 19), an ultrasound probe (FIG.20) and an RF based probe (FIG. 21), for example as used in the experiments described hereinabove.

In some embodiments, at least a distal portion of each of the probes described is narrow enough to enable its insertion, at least in part, into the external ear canal. For example, a diameter of a distal portion of the probe is between 0.5mm-5 mm, 2mm-6mm, 5mm- 12mm, or intermediate, larger or smaller diameter.

FIG. 19 shows an exemplary light based probe structure, according to some embodiments. In some embodiments, probe 1900 comprises a tapering body 1902, optionally cone shaped. In some embodiments, the body is solid.

In some embodiments, a cylindrical extension 1904 extends from the narrow end of the body. In some embodiments, a light conducting channel 1906 extends axially along the length of the body and the cylindrical extension. Optionally, an imager (not shown) is positioned at a proximal end of the body.

In some embodiments, the probe comprises one or more light sources 1908, for example, LEDs. In some embodiments, the light sources are mounted on a proximal portion of the body, and are directed towards the distal end. In some embodiments, for example as shown in this figure, a plurality of light sources (e.g. 2, 3, 4, 6, 8, 12, 16 or intermediate, higher or smaller number) are arranged on a head 1912 of the body, optionally arranged circumferentially around a circular head. Optionally, the light sources are arranged at selected intervals from one another. The intervals may be constant, as shown in this example (where 4 LEDs are configured such that each pair of LEDS are located on diametrically opposing positions); or, in some embodiments, the light sources are arranged with non-constant intervals. In some embodiments, a light conducting channel 1910 extends from each of the light sources to the distal end of the probe, for illumination of the tympanic membrane.

It is noted that in some embodiments, light is transferred via the probe body itself, for example via walls of a body comprising or formed of transparent or semitransparent material(s). Optionally, the probe includes no designated light conducting channels. Optionally, only a central channel extends axially along the body, for example through which imaging is performed.

FIG. 20 shows an exemplary ultrasound probe structure, according to some embodiments.

In some embodiments, ultrasound probe 2000 comprises a tubular body 2002 ending with a tapering geometry, such as a cone 2004. Optionally, the cone is separable from the body, for example attached to the body via a rotatable nut 2008 and/or other separable coupling.

In some embodiments, one or more ultrasound elements 2006 are placed within the tubular body. In some embodiments, the ultrasound element comprises a piezoelectric transducer. In the example used in the experiment, a UST-40T ultrasonic ceramic piezoelectric transducer was used. In some embodiments, the ultrasound element is configured for emitting and/or receiving signals to and/or from the ear, such as to and/or from the tympanic membrane. In some embodiments, properties of the emitted ultrasound such as intensity, frequency, duration of emission and/or others are suitable for producing a reflection (returning echoes) from the tympanic membrane and/or from other middle and/or inner structures, such as one or more bones inside the ear.

In some embodiments, the probe comprises circuitry (not shown) for excitation of the ultrasound element and/or for transferring of the signals received by the ultrasound element.

It is noted that in some embodiments, more than one ultrasound element is used. Optionally, one element is used for emitting ultrasound signals, and another element is used for receiving ultrasound signals.

In some embodiments, during use, the probe is introduced to the ear such that contact with the tympanic membrane is made. Additionally or alternatively, a liquid or gel medium is placed intermediate the ultrasound element and the tympanic membrane. Optionally, the probe itself comprises a liquid, for example contained at a distal tip of the probe. Additionally or alternatively, a liquid or gel are inserted into the ear prior to introducing of the probe, to provide a fluid medium suitable for transferring of the ultrasound signals through.

FIG. 21 shows an exemplary RF probe structure, according to some embodiments.

In some embodiments, probe 2100 comprises a body 2102 tapering towards an extension 2104, optionally cylindrical, at its distal end. In some embodiments, an inner channel or lumen 2108 extends along the body and the extension.

In some embodiments, an RF assembly 2110 of the probe comprises conductive elements, for example conductive coils 2106. In some embodiments, the coils are disposed circumferentially around the cylindrical extension 2104, for example, surrounding the extension.

In some embodiments, as also shown in the detailed view of the RF assembly, a diamagnetic insert 2112 is positioned in between the two coils. In some embodiments, the diamagnetic insert is shaped as a ring. In some embodiments, the diamagnetic insert comprises or is formed of a material suitable for reducing or preventing an electric effect of one coil on the other. In an example, the diamagnetic insert is formed of aluminum. In some embodiments, the coils and the insert are arranged externally to extension 2104, for example positioned radially outwardly to the walls of extension 2104 (and thereby radially outwardly to the inner channel 2108).

In some embodiments, in addition to the RF assembly, an imager (not shown) may be mounted at a proximal position and directed towards the distal end of the probe. Optionally images of the tympanic membrane are obtained by the imager via the inner channel 2108. In some embodiments, one or more light sources are positioned and directed towards the distal end of the probe, for illumination of the ear, such as for the purpose of examination and/or for positioning of the probe and/or for enabling acquiring of images.

The terms "comprises", "comprising", "includes", "including", “having” and their conjugates mean "including but not limited to".

The term“consisting of’ means“including and limited to”.

The term "consisting essentially of" means that the composition, method or structure may include additional ingredients, steps and/or parts, but only if the additional ingredients, steps and/or parts do not materially alter the basic and novel characteristics of the claimed composition, method or structure.

As used herein, the singular form "a", "an" and "the" include plural references unless the context clearly dictates otherwise. For example, the term "a compound" or "at least one compound" may include a plurality of compounds, including mixtures thereof. Throughout this application, various embodiments of this invention may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

Whenever a numerical range is indicated herein, it is meant to include any cited numeral (fractional or integral) within the indicated range. The phrases“ranging/ranges between” a first indicate number and a second indicate number and“ranging/ranges from” a first indicate number“to” a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numerals therebetween.

As used herein the term "method" refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts.

As used herein, the term“treating” includes abrogating, substantially inhibiting, slowing or reversing the progression of a condition, substantially ameliorating clinical or aesthetical symptoms of a condition or substantially preventing the appearance of clinical or aesthetical symptoms of a condition.

It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements.

All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention. To the extent that section headings are used, they should not be construed as necessarily limiting.

In addition, any priority document(s) of this application is/are hereby incorporated herein by reference in its/their entirety.