SYSTEMS AND METHODS FOR PHOTOBIOMODULATION

Abstract

The present application is directed to systems, devices, and methods for diagnosing, preventing, and treating diseases and disorders through photobiomodulation therapy, either alone or in combination with one or more other therapies. More particularly, the present invention provides photon source devices configured to deliver light to a portion of an organism, which causes a physiological response within that light exposed organism. The invention also provides a system which includes one or more photon source devices and functionality for diagnosing or assessing a disease or disorder, and for monitoring responsiveness of the disease or disorder to treatment with the therapeutic light. Additionally, this application is directed to utilizing the present systems and devices in combination with known adjunctive therapies including devices, services, drugs, biologics, genetics and supplements to produce synergistic optimal therapeutic outcomes.

Claims

1. A method for using a photobiomodulation photon source system to deliver photon energy applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves to trigger cellular processes that prevent apoptosis and restore homeostasis, comprising the steps of: (a) applying a photon energy delivery to one or more of a subject's cells, tissues, organs, bodily fluids and nerves; and (b) delivering another therapy in parallel with the delivery of said applied photon energy; wherein the application of photon energy to one or more of a subject's cells, tissues, organs, bodily fluids and nerves in combination with the delivery of another therapy in parallel thereby acts to synergistically bring about physiological changes within said one or more of a subject's cells, tissues, organs, bodily fluids and nerves resulting in the improvement and maintenance of a health state including a disease state.

2. The method for using a photobiomodulation photon source system to deliver photon energy applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves to trigger cellular processes that prevent apoptosis and restore homeostasis according to claim 1, wherein the bioavailability of another therapeutic compound is further regulated by photon energy delivery induced changes at the molecular, cellular and tissue levels that affect cellular response and compound bioavailability.

3. The method for using a photobiomodulation photon source system to deliver photon energy applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves to trigger cellular processes that prevent apoptosis and restore homeostasis according to claim 1, wherein the bioavailability of another active therapeutic compound is further regulated by photon energy delivery inherently introduced heat-induced chemical and biophysical changes that further alter blood perfusion and cellular absorption rates to regulate another therapeutic compound bioavailability.

4. A method for using a photobiomodulation photon source system to deliver photon energy applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves to affect the cellular energy and oxidative species homeostasis, comprising the steps of: (a) applying a photon energy delivery to one or more of a subject's cells, tissues, organs, bodily fluids and nerves for the purpose of affecting physiological changes within said one or more of a subject's cells, tissues, organs, bodily fluids and nerves; and (b) delivering an active therapeutic compound; wherein the application of photon energy to one or more of a subject's cells, tissues, organs, bodily fluids and nerves thereby acts to further regulate the efficacy of another therapeutic active compound by inducing physiological changes within said one or more of a subject's cells, tissues, organs, bodily fluids and nerves resulting in the improvement and maintenance of a health state including a disease state.

5. The method for using a photobiomodulation photon source system to deliver photon energy applied to one or more of a subject's tissues, organs, bodily fluids and nerves to affect the cellular energy and oxidative species homeostasis according to claim 4, wherein the efficacy of another active compound is further regulated by photon energy delivery induced changes at the molecular, cellular and tissue levels that modulate and alter the concentrations of intracellular chemical and biological agents, directly and indirectly involved in reactions with another therapeutic compounds and associated effects, to regulate compound efficacy changes.

6. The method for using a photobiomodulation photon source system to deliver photon energy applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves to affect the cellular energy and oxidative species homeostasis according to claim 4, wherein the efficacy of another active compound is further regulated by photon energy delivery temperature changes and subsequent alterations of the concentrations of intracellular chemical and biological agents, directly and indirectly involved in reactions with active compounds and associated effects, to further regulate another compound efficacy.

7. A method for using a photobiomodulation photon source system in combination with one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves, comprising the steps of: (a) providing a photobiomodulation system photon source device capable of communicating with other devices wirelessly; (b) pairing said photobiomodulation system photon source device with a subject's profile using a software application and a data management and analytic system; (c) placing and positioning said photobiomodulation system photon source device using a fitted bio-interface and one or more placement sensors; (d) activating adjusted photon emissions from one or more light sources and delivering a quantity of photonic energy to a subject's tissues; and (e) applying one or more combination therapies to one or more of a subject's cells, tissues, organs, bodily fluids and nerves; wherein the method for using said photobiomodulation photon source system in combination with said one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluid and nerve cells when paired to said software application and said data management and analytic system enables modulation of the subject's physiological state and development of optimally customized protocols for diagnostic and preventative therapy treatments through the evaluation of resulting Changes in the physiological state of one or more subjects following the delivery of photonic energy.

8. The method for using a photobiomodulation photon source system in combination with one or more other therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves, according to claim 7, wherein said one or more other therapies are applied systemically.

9. The method for using a photobiomodulation photon source system in combination with one or more other therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves according to claim 7, wherein said one or more other therapies are applied locally.

10. The method for using a photobiomodulation photon source system in combination with one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves according to claim 7, wherein said one or more other therapies are applied trans-tympanically.

11. The method for using a photobiomodulation photon source system in combination with one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves according to claim 7, wherein said one or more other therapies are applied orally.

12. The method for using a photobiomodulation photon source system in combination with one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves according to claim 7, wherein said one or more other therapies are applied parenterally.

13. The method for using a photobiomodulation photon source system in combination with one or more therapies applied to one or more of a subject's cells, tissues, organs, bodily fluid and nerve cells according to claim 7, wherein said one or more other therapies are applied topically.

14. The method for using a photobiomodulation photon source system in combination with one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves according to claim 7, wherein said one or more other therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves regulate cellular function in said subject's tissues, organs, bodily fluid and nerve cells.

15. The method for using a photobiomodulation photon source system in combination with one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves according to claim 7, wherein said one or more other therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves further includes a therapeutic medication compound.

16. The method for using a photobiomodulation photon source system in combination with one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves according to claim 7, wherein said one or more other therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves further includes therapeutic non-medication compounds and treatments.

17. The method for using a photobiomodulation photon source system in combination with one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves, according to claim 15, wherein said one or more other therapies applied regulates cellular function in said subject's cells, tissues, organs, bodily fluid and nerve cells further includes therapies which regulate reactive oxygen species, anti-apoptosis, cellular inflammatory response and anti-oxidant agents.

18. The method for using a photobiomodulation photon source system in combination with one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves, according to claim 17, wherein said other therapies applied which regulate reactive oxygen species and cellular inflammatory response further include, free radical scavengers and steroids.

19. The method for using a photobiomodulation photon source system in combination with one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves, according to claim 17, wherein said other steroid therapies includes dexamethasone.

20. The method for using a photobiomodulation photon source system in combination with one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves, according to claim 15, wherein said one or more other therapies applied regulates cellular function in said subject's cells, tissues, organs, bodily fluid and nerve cells further includes therapies which regulate neurotransmission including neurotransmission modulators.

21. The method for using a photobiomodulation photon source system in combination with one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves, according to claim 21, wherein said neurotransmission modulator therapies includes antiemetics and anxiolytics.

22. The method for using a photobiomodulation photon source system in combination with one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves, according to claim 20, wherein said other therapies which include neurotransmission modulators further includes calcium channel modulators, 5-HT3 receptor antagonists, NK1 receptor antagonists, sodium and calcium ion channel modulators and psychoactive pharmaceuticals.

23. The method for using a photobiomodulation photon source system in combination with one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves, according to claim 15, wherein said one or more other therapies applied regulates cellular function in said subject's cells, tissues, organs, bodily fluid and nerve cells further includes therapies which regulate cell growth stimulators.

24. The method for using a photobiomodulation photon source system in combination with one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves, according to claim 23, wherein said other therapies applied which regulate cell growth stimulators further include bone marrow stimulators, epidermal growth factor, gamma secretase inhibitor, WNT antagonists, and LATS kinases.

25. The method for using a photobiomodulation photon source system in combination with one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves, according to claim 15, wherein said one or more other therapies applied regulates cellular function in said subject's cells, tissues, organs, bodily fluid and nerve cells further includes therapies which regulate sirtuin proteins.

26. The method for using a photobiomodulation photon source system in combination with one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluids and nerves, according to claim 15, wherein said one or more other therapies applied regulates cellular function in said subject's cells, tissues, organs, bodily fluid and nerve cells further includes stem cell therapy.

27. The method for using a photobiomodulation photon source system in combination with one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluid and nerve cells, according to claim 16, wherein said other therapeutic non-medication compounds and treatments further includes the administration of dietary supplements.

28. The method for using a photobiomodulation photon source system in combination with one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluid and nerve cells, according to claim 27, wherein said dietary supplement includes zinc gluconate.

29. The method for using a photobiomodulation photon source system in combination with one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluid and nerve cells, according to claim 16, wherein said therapeutic non-medication treatments further include a non-medication service therapy, cognitive behavior therapy, coping skills and activities, meditation, sleep treatments, stress treatments, yoga and acupuncture.

30. The method for using a photobiomodulation photon source system in combination with one or more combination therapies applied to one or more of a subject's cells, tissues, organs, bodily fluid and nerve cells, according to claim 16, wherein said therapeutic non-medication compounds and treatments further includes non-medication electromagnetic therapy and non-medication acoustical energy therapy.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0148] The accompanying drawings, which are incorporated in and form a part of this specification, illustrate embodiments of the Systems and Methods for Photobiomodulation and together with the description, serve to explain the principles of this application.

[0149] FIG. 1 depicts a cross-sectional schematic view of the photobiomodulation device inserted in a subject's ear canal.

[0150] FIG. 2 depicts a photobiomodulation device configured to apply the device diagnostic and therapeutic capabilities to one or both of a subject's ears, including a light source in communication with a smartphone or like device, both of which are connected to the two photobiomodulation devices.

[0151] FIG. 3 depicts a detailed cross-sectional view of a subject's ear anatomy with a photobiomodulation device inserted into the ear canal.

[0152] FIG. 4 depicts an enlarged cross-sectional detailed view of a photobiomodulation device which operates and communicates wirelessly and is powered by an on-board battery.

[0153] FIG. 5 depicts an enlarged cross-sectional detailed view of a photobiomodulation device which operates and communicates wirelessly and is powered by an on-board battery as well as an external wired power source.

[0154] FIG. 6 depicts an enlarged cross-sectional detailed view of a photobiomodulation device which operates and communicates wirelessly, has an external light source connection, and is powered by an on-board battery as well as an external wired power source.

[0155] FIG. 7A depicts a photobiomodulation device configured in a dual device for insertion into one or both of a subject's ears, including a light source in communication with a smartphone or like device, both of which are connected to the two photobiomodulation devices.

[0156] FIG. 7B depicts a photobiomodulation device configured in a head set style dual device for insertion into both of a subject's ears, including a light source in wireless communication with a smartphone or like device.

[0157] FIG. 7C depicts a photobiomodulation device configured in a head set style dual device for insertion into both of a subject's ears including a light source in communication with a smartphone or like device, both of which are connected to the two photobiomodulation devices.

[0158] FIG. 8 depicts a schematic diagram of the photobiomodulation system bus illustrating the numerous communications capabilities between the system bus and the hardware elements integrated into the photobiomodulation device.

[0159] FIG. 9 depicts a schematic diagram of the various telecommunications capabilities of the PBMT device either alone or coupled to a smartphone utilizing a smartphone application (APP) or other like computing device.

[0160] FIG. 10 depicts a flow chart illustrating the system architecture interrelationships between the human/biointerface, the photobiomodulation device and the external data sets and inputs which are cloud based and located on a smartphone application (APP), for facilitating analytics performed by the photobiomodulation system.

[0161] FIG. 11 depicts a flow chart illustrating the setup/authorization steps in which a subject or authorized third party can create a subject profile, import external data and pair an external device to create diagnostic and therapeutic protocols.

[0162] FIG. 12 depicts a flow chart illustrating the steps taken in a hearing restoration and/or protection configuration having the diagnostic and therapeutic functionality initiated with only insertion location sensing capability enabled in the photomodulation device.

[0163] FIG. 13 depicts a flow chart illustrating the steps taken in a hearing restoration and/or protection configuration having the diagnostic and therapeutic functionality initiated with all sensing capabilities enabled in the photomodulation device.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0164] As required, the detailed embodiments of the present Systems and Methods for Photobiomodulation 10A, 10B, 10C, 10D, 100, 200 and 300 are disclosed herein, however, it is to be understood that the disclosed embodiments are merely exemplary of the design that may be embodied in various forms. Therefore, specific functional and structural details disclosed herein are not to be interpreted as limiting, but merely as basic for the claims and as a representative basis for teaching one skilled in the art to variously employ the present design in virtually any appropriately detailed structure as well as combination.

[0165] Referring now to FIG. 1, there is depicted a cross-sectional schematic view of an exemplary photobiomodulation system photon source device 10A inserted into an ear canal of a subject. Generally, a photobiomodulation system photon source device 10A comprises a housing 12 with an interior section 14 including a light source 16 and a waveguide 18 configured to emit a quantity of a therapeutic light 20 in one or more wavelengths therefrom. A plurality of placement sensors 22 and 24 configured to detect that the photobiomodulation system photon source device 10A is properly positioned for use, and a proximity sensor 26 are connected to a control system 28 that operably connects a power source 30 to the light source 16. The photobiomodulation system photon source device 10A may also include a light modulator 32 on the end of waveguide 18 which illuminates light outward from aperture 16 in the device protective cover 34. The photobiomodulation system photon source device 10A may also include a microphone/receiver 36 and speaker 38, and comprise one or more means for aiming and/or guiding the therapeutic light down the ear canal for delivery to the middle ear and/or the inner ear (see details of this function discussed below).

[0166] Referring now to FIGS. 1, 4, 5, and 6, there are depicted a schematic of an exemplary photon source device 10A inserted into an ear canal of a subject as shown in FIG. 1, a cross-sectional view of a first embodiment PBMT device 10B as shown in FIG. 4, a second embodiment PBMT device 10C as shown in FIG. 5, and a third embodiment PBMT device 10D as shown in FIG. 6 of a photobiomodulation system photon source device (hereinafter photon source device) configured for use to deliver photobiomodulation therapy (hereinafter PBMT) to an ear of a subject. As shown in FIG. 4, a photon source device 10B comprises a housing 12 with an interior 14 which contains a plurality of components described in detail below. In embodiments, the housing 12 includes a form factor having fitting bio-interfaces 40 and 42 which is configured for insertion into an ear and/or an ear canal of the subject for PBMT operations, as may be used for treatment, prevention, diagnosis, evaluation of hearing loss, SNHL, tinnitus, ear ringing, or any combination thereof.

[0167] In embodiments, the photon source device 10B may be fitted to the subject, such that a distance between a light source 16 and the portion of the subject is controlled to optimize the safe and effective PBMT therapeutic light delivered. Because different subjects may have substantially different anatomies, optimal safe and effective PBMT therapy may require the photon source device 10A and 10B to be custom fitted to a particular anatomical structure of the subject. As a non-limiting example, if the PBMT system is used to diagnose, prevent, restore hearing loss and/or treat SNHL, then the photon source device 10B may be configured to be positioned within one or both ear canals of the subject for treatment of the middle ear, the inner ear, or both. Similarly, if the PBMT system is used to diagnose, prevent, and/or treat oral mucositis, then the photon source device 10B may be configured to be positioned within the mouth of the subject for treatment of the oral mucosal membranes. Accordingly, in embodiments of the PBMT system, the photon source device 10B may be custom fitted to an ear of the subject to deliver the therapeutic light to and through a tympanic membrane of the ear of the subject, or alternatively, may be custom fitted to a mouth of the subject to deliver the therapeutic light to a mucous membrane of the mouth of the subject. The photon source device 10B may utilize materials to custom fit to the patient's body location including coatings, disposable covers, malleable materials, and/or materials that are formed to fit the patient's specific body location, e.g., by a separate method.

[0168] In embodiments, the photon source device 10B may comprise a protective cover 34 which is seated about one or more fitted bio-interfaces 40 and 42. The protective cover 34 may include a forward aperture 33 on a forward end thereof, through which the therapeutic light from the light source 16 passes after beam formation at a light modulator 32. In embodiments, the forward aperture 44 may have a defined impact on the light signal, such as through one or more of attenuation and disbursement of the light signal. In addition, the protective cover 34 may be reusable or single-use, and in this manner, the photon source device 10B may be used by one subject only, or may be used by more than one subject without cross-contamination between subjects.

[0169] In embodiments, the photon source device 10B comprises a light source 16 configured to emit an optimal safe and effective quantity of the therapeutic light therefrom, a plurality of placement sensors 22 and 24 configured to detect that the photon source device 10B is positioned for use, and a control system 28 that operably connects a power source 30 to the light source 16. The photon source device 10B may be configured to emit one or more wavelength of light, e.g. red light, near-IR light, or both, among others; in embodiments, the photon source device 10B may be configured to emit light having one or more wavelengths including, but not necessarily limited to: 447 nm, 532 nm, 635 nm, 808 nm, and any combination thereof.

[0170] In embodiments, the plurality of positioning sensors 22 and 24 may be configured to detect whether the photon source device 10B is placed for use, and may conditionally emit one or more signals which communicate to the subject and/or another individual whether the device is correctly positioned. In embodiments, one or more placement sensors 22 and 24 may detect the location of the device inside the ear canal of the subject, and one or more proximity sensors 26 may detect a particular distance from the light source 16 to the portion of the subject's body to receive therapeutic light thereon, e.g., the tympanic membrane.

[0171] In embodiments, one or more placement sensors of the plurality of placement sensors 22 and 24 may emit an electronic signal, emit an audio signal, emit a visual signal, emit a haptic and/or tactile signal, complete an electronic circuit, or otherwise change or alter a state or a configuration of the photon source device 10B or the control system 28, when one or more of the sensors are activated. In embodiments, the one or more placement sensors 22 and 24 may be activated if the device is inserted into the ear canal, and the one or more proximity sensors 26 may be activated if the device is appropriately distanced from the portion of the subject's body to receive therapeutic light thereon. In embodiments, all sensors may need to be activated before using the photon source device 10B. In this manner, the photon source device 10B may be unable to be activated unless correctly positioned for use for the safe and effective delivery of therapeutic light.

[0172] In embodiments, the photon source device 10B may utilize a form of haptic feedback (e.g., kinesthetic communication) during one or more stages of operation, such as the photon source device 10B being properly placed, starting, delivering energy, working, stopping, and any combination thereof. In this manner, the subject, or another individual such as a caretaker, may operate the photon source device 10B using the sense of touch. In embodiments, the photon source device 10B may include one or more sensing means, of a plurality of sensing means, which measures noise exposure over time.

[0173] In embodiments, the plurality of placement sensors 22 and 24 may comprise a sensing means (e.g., a placement sensor) which detects proper placement of the photon source device 10B into an orifice (e.g., in an ear or in an ear canal) of a subject. In embodiments, the sensing means may be comprised of one or more suitable mechanisms, including but not necessarily limited to light and/or optical detection, detection of a mechanical change, detection of an electrical change, and/or detection of a galvanic skin response. In embodiments, the sensing means may need to be activated before the light source 16 is fully activated, to ensure the photon source device 10B is safely positioned for optimal therapeutic effect before use.

[0174] In embodiments, the sensing means may include, but may not necessarily be limited to, one or more skin color and skin condition sensors, one or more pulse oximetry SpO2 sensors, one or more StO2 sensors, one or more sensors capable of obtaining SmO2 measurements, one or more optical sensors, one or more optical imaging arrays, one or more heart rate (HR) sensors, one or more heart rate variability (HRV) sensors, one or more respiration rate sensors, one or more compression sensors, one or more electrodermal activity sensors (e.g., galvanic skin response (GSR) or galvanic skin conductance), one or more temperature sensors (e.g., skin, tympanic membrane), one or more sensors capable of measuring one or more neurological signals, one or more neural electrical impulse activity (EEG) sensors, and any combination thereof. In embodiments, the photon source device 10B may employ one or more sensing means to detect the presence of otitis media, cerumen (ear wax), other growths, foreign media, tympanic membrane surface/changes, ear canal topology, tympanic membrane topology or other conditions within the ear before, during, or after use of the invention.

[0175] In embodiments, the plurality of sensing means may comprise the proximity sensor 26 which automatically or upon command measures a distance between the light source 16 and the portion of the subject's body. In embodiments, the proximity sensor 26 may comprise a time-of-flight (TOF) sensor. The proximity sensor 26 may be operably connected to the control system 28, a control circuit of the photon source device 10B, or both, in order to enable safe and effective delivery of the therapeutic light to the portion of the subject's body.

[0176] In embodiments, the TOF sensor (e.g., 26) may include one or more components designed to determine the distance from the light source 16 to the portion of the subject to receive the PBMT treatment (e.g., skin, tympanic membrane). In embodiments, the TOF sensor may include any suitable optical, acoustic, or electromagnetic transmitter and receiver, or any combination thereof. In embodiments, the TOF sensor may include one or more photodetectors, photodetector arrays, microphones, antennae, and the like. One function of the TOF sensor is to detect if the photon source device 10B is properly positioned with the subject's body to deliver a safe and effective PBMT treatment prior to or during the treatment, and may operate inside the subject's ear, inside the subject's mouth, next to the subject's skin, or at another position within or adjacent to the subject. Another function of the TOF sensor is to detect if the photonic illumination plane orientation to deliver the optimal safe and effective PBMT.

[0177] In embodiments, the control system 28 may include an aperture 44 thereon, through which a component, such as an electrical wire, may pass which operably connects a power source 30 (e.g., a battery or a rechargeable battery) to the control system and/or light source 16. In this manner, the aperture 33 may facilitate insertion of an electronic or electrical component, or a portion thereof, therethrough, as may be needed during assembly of the photon source device 10B. In embodiments, the control system 28 may be operably connected to the power source 30 and the light source 16 and may be configured to control the photon source device 10B or an operation or method thereof. In embodiments, the light source 16 may be configured to deliver a safe and effective quantity of a therapeutic light to a portion of a subject, and to operate according to the control system 28.

[0178] In embodiments, the light source 16 may be comprised of one or more suitable sources of therapeutic light and may include one or more of any organic or inorganic light source. The light source 16 may be coherent, non-coherent, or both coherent and non-coherent. In embodiments, the light source 16 may be any suitable source of electromagnetic radiation, such as a light-emitting diode (LED), a laser, an incandescent light, a fluorescent light, a compact fluorescent light, one or more chemiluminescent compositions, one or more electrochemiluminescent compositions, a high-intensity discharge light, a halogen light, another suitable light source, or any combination thereof. In addition, it is contemplated herein that embodiments of the invention may be designed for reuse, and other embodiments of the invention may be designed for single use.

[0179] In embodiments, the photon source device 10B may be wearable by a subject, such that if the photon source device 10B is worn by the subject, the plurality of positioning sensors 22 and 24 detect that the photon source device 10B is positioned for optimal safe and effective use. In embodiments, the photon source device 10B may include any form factor suitable for its intended use, including but not necessarily limited to an ear insert form factor (e.g., as shown in FIGS. 4, 5, and 6), a behind the ear form factor, an over-the-ear form factor, a mouthpiece form factor, a handheld form factor, a general form factor which may be used to treat any part of the body, and the like. In this manner, the photon source device 10B may be worn by the subject while the subject performs other tasks, and therapy may be delivered on a constant or regular basis throughout a period.

[0180] In embodiments, the photon source device 10B may also comprise a light modulator 32. The light modulator 32 may be configured to convert a first wavelength of light into one or more second or additional wavelengths of light to produce the optimal safe and effective PBMT for the physiological state of the subject. In embodiments, any suitable optical mechanism for modulating light may be utilized for the light modulator 32, including but not necessarily limited to one or more filters, one or more waveguides, one or more quantum dots, one or more lenses, and any combination thereof. In this manner, the photon source device 10B may be configured to deliver an optimal safe and effective PBMT in a particular treatment mode of operation of the device.

[0181] In embodiments, the photon source device 10B may comprise a control system 28 operably connected to the photon source device 10B, and the control system 28 may be partially or completely integral with the photon source device 10B. In embodiments, the control system 28 may be configured to control at least part of the photon source device 10B. The control system 28 may include computer hardware and software elements to enable partially and/or fully automated control of the photon source device 10B, as may be desired to perform one or more methods of the invention. In embodiments in which the control system 28 is partially integrated with the photon source device 10B, some portion of the control system 28 may reside on or with the photon source device 10B and some other portion of the control system 28 may reside on or with another device, such as a personal computing device (e.g., smartphone, smart watch, computer), or a networked computer system, e.g., as may be utilized as part of a treatment service. In embodiments having full integration of the control system 28 with the photon source device 10B, the entire control system 28 may reside on or with the photon source device 10B, and in this manner, the control system 28 may be fully integrated with the photon source device 10B for localized control of the device during use. In embodiments, the control system may be configured to enable local control, remote control, or both local and remote control, according to a particular implementation. In embodiments, one or more operable connections between the control system 28 (or a component thereof) and the photon source device 10B may be wired, wireless, or any combination thereof. In embodiments in which the control system 28 is in wireless communication to the photon source device 10B, a split control system 28 may be utilized, wherein part of the control system 28 is local and part of the control system 28 is remote. In embodiments, one or more wireless connections of the invention may include one or more optical connections, one or more radiofrequency (RF) connections, one or more acoustic connections, one or more Wi-Fi connections, one or more Bluetooth® connections, one or more cellular connections, or any combination thereof.

[0182] In embodiments, the photon source device 10B may be capable of sensing and generating acoustic frequencies with an in-ear microphone/receiver 36 and speaker 38, or one or more similar devices. The microphone/receiver 36 and speaker 38 may be utilized to detect auditory acuity changes (e.g., gains and losses) over time, including changes in the ability to hear different sound frequencies as well as different sound intensities the subject is exposed to during a period of time. Along with the other components of the system, the microphone/receiver 36 and speaker 38 provide data to determine the physiological state of the subject, such as auditory acuity, and/or to detect total ambient sound exposure during use and/or during the time between applications of the PBMT therapy, for example. Accordingly, the microphone/receiver 36 and speaker 38 may be present in embodiments for which the intended use is diagnosis, evaluation, treatment, restoration and/or prevention of hearing loss, particularly sensorineural hearing loss, tinnitus and/or ear ringing.

[0183] In embodiments, the photon source device 10B may be integral with another device, such as a device that protects the ear from excessive sounds and/or reduces ambient sound (e.g. industrial/military protective headphones, noise cancellation headphones). In embodiments, the photon source device 10B may cooperate with the protective headphones to deliver PBMT to prevent and/or restore hearing loss, SNHL, tinnitus, and/or ear ringing. In this manner, through the use of such a combination, a subject wearing a combinatorial device may experience lower environmental noise and have a lower risk for hearing loss, and may also receive PBMT to prevent or treat hearing loss, SNHL, tinnitus, or ear ringing. In embodiments, the combinatorial device may sense noise exposure directly, or receive input from another device (e.g., a computer, a cellular phone, etc.) communicating noise exposure to form a singular and/or a cumulative data set for noise exposure; such a singular and/or cumulative data set may be utilized by the combinatorial device to determine the optimal safe and effective therapy which may be required by the subject for a period of time, e.g., daily, weekly, monthly, or some other period of time.

[0184] In embodiments, a waveguide 18 is positioned between the light source 16 and the light modulator 32. The waveguide 18 may be any structure that guides light waves from the light source 16 to the light modulator 32 with minimal loss of energy by optimizing the delivery of light energy to the subject. The waveguide 18 may be necessary to maintain and/or define the amount of light delivered to the light modulator 32, and in this manner, a defined quantity of light may be available for modulation by the light modulator 32 prior to illuminating the selected subject's body location.

[0185] In embodiments, a light source aimer and/or collimating feature 46 may be included in the photon source device. The light source aimer and/or collimating feature 46 may be any suitable structure for adjusting one or more angles of one or more of the light sources 16, the waveguide 18, and the light modulator 32. Because different subjects have different anatomical shapes of ear canals, one or more angles of the waveguide 18 may need to direct the optimal therapeutic light from the light source 16 toward the selected tissue, e.g. tympanic membrane, cochlea, etc. Exemplary angles that may be adjusted by the light source aimer and/or collimating feature 46 include an angle about a vertical axis, an angle about a horizontal axis, and any combination thereof.

[0186] Now referring to FIG. 5 and FIG. 6, in embodiments, the photon source device 10D includes a stem 48 which may be hollow and include a stem aperture 50 on a lower portion thereof. The stem 48 may be sized to enable one or more wires and/or fiberoptic cables to pass therethrough. Exemplary wires which may pass through the stem 48 and the stem aperture 50 include a cable 54 carrying one or more wave guides transmitting light from an external light source, a wire such as a control wire 52 carrying electrical power from an external power source, a wire from a partial of completely external control system, and any combination thereof. In the embodiment of FIG. 6, the photon source device 10D may be a self-contained earphone embodiment, and in such an embodiment, the stem 48 and/or the stem aperture 50 may be omitted from a particular design as needed. In the embodiment of FIG. 5, the photon source device 10C may be a semi-contained earphone embodiment, wherein control of the photon source device 10C is achieved through an external control mechanism and/or wherein power is delivered to the control system 28 by the control wire 52. In the embodiment of FIG. 6, the photon source device 10D may be an externally-controlled earphone embodiment, wherein control and power are relayed by the control wire 52 and wherein light is delivered from the external light source by the cable 54, which may be a fiberoptic cable.

[0187] In embodiments, the control system 28 may comprise a non-transitory computer-readable storage medium with instructions encoded thereon which, when executed by a processor, causes a PBMT system which comprises the photon source device 10A-10D to perform all or part of a method of the invention. In embodiments, the method may be wholly or partially performed by the control system 28 and the photon source device 10A-10D. In this manner, the method may be completely performed by a system of the invention, or alternately, may be partially performed by the system of the invention.

[0188] FIG. 2 depicts a combination photobiomodulation/smartphone device 100 configured in a dual photon source device 10A for insertion into one or both of a subject's ears, including a control feature/light source 120 in communication with a smartphone 102 or like device, both of which are connected to the two photobiomodulation devices via a wired connection 122 (see FIG. 5 below).

[0189] FIG. 3 depicts a detailed cross-sectional view of a subject's ear anatomy with a photobiomodulation system photon source device 10A inserted into the ear canal illustrating the illumination of therapeutic light 20 into the subject's tympanic membrane, middle ear, cochlea and inner ear.

[0190] Referring now to FIG. 2 and FIG. 3, there are depicted an illustration of an exemplary PBMT combination photobiomodulation/smartphone system 100 as shown in FIG. 2, and an illustration of the exemplary PBMT system photon source device 10A in use to diagnose, prevent, restore hearing loss and/or treat a hearing condition as shown in FIG. 3. In embodiments, a computer system 102 (e.g., one or more of a personal computer, a tablet, a cellular phone, a smartphone, and the like) is operably connected to one or more photon source devices 10A via connection 122. In embodiments, connection 122 may be a wired connection, a wireless connection, an RF connection, an audio connection, an optical connection, or any other connection type or combination thereof. In embodiments, a control feature 120 (which may comprise all or part of the control system) may be included to enable full or partial control of the photon source device 10A and/or a control system of the invention. To use the photon source device 10A to diagnose, prevent, restore hearing loss and/or treat a hearing condition, the photon source device 10A is inserted into one or both ear canals of a subject, as shown in FIG. 3. Upon inserting the photon source device 10A into the ear canal, one or more sensors of a plurality of sensors may be triggered to enable the photon source device 10A to be activated, as described elsewhere herein. In this manner, the photon source device 10A may be activatable if correctly positioned for use.

[0191] FIG. 4 depicts an enlarged cross-sectional detailed view of a photobiomodulation device 10B which operates wirelessly and is powered by an on-board battery power source 30, and is discussed in greater detail above.

[0192] FIG. 5 depicts an enlarged cross-sectional detailed view of a photobiomodulation device 10C which operates wirelessly and is powered by an on-board battery 30 as well as an external wired power/control source wire 52, and is discussed in greater detail above.

[0193] FIG. 6 depicts an enlarged cross-sectional detailed view of a photobiomodulation device 10D which operates wirelessly, has an external light source connection, and is powered by an on-board battery 30 as well as an external wired power/control source wire 52, and a fiber optic light source 54, and is discussed in greater detail above.

[0194] FIG. 7A depicts a combination photobiomodulation/smartphone system 100 photobiomodulation device 10C configured in a dual device for insertion into one or both of a subject's ears, including a light source 120 in communication with a smartphone or like device via a wired connection 122, both of which are connected to the two photobiomodulation devices 10C.

[0195] FIG. 7B depicts a combination photobiomodulation/headset system 200 configured in a head set 224 style dual devices 10B for insertion into both of a subject's ears, including a self-contained control feature/light source 226 in wireless communication with a smartphone or like device.

[0196] FIG. 7C depicts a combination photobiomodulation/smartphone/headset system 300 configured in a head set 324 style dual device 10D for insertion into both of a subject's ears including a light source 320 in communication with a smartphone 302 or like device, both of which are wire 322 connected to the two photobiomodulation devices.

[0197] Referring now to FIG. 7A, FIG. 7B, and FIG. 7C, there are depicted illustrations of a first (FIG. 7A), a second (FIG. 7B), and a third (FIG. 7C) exemplary combination PBMT systems according to the present invention. In embodiments, the PBMT system may include an “ear bud” form factor 10A-10D, configured to be inserted into the ear canal of the subject (FIG. 7A). In embodiments, the photon source device(s) 10A-10D may be operably connected to the smartphone/computer system 102 via connection 122, which may be a wired connection, a wireless connection, an RF connection, an audio connection, an optical connection, or any other connection type or combination thereof. In embodiments, a control feature/light source 120 (which may comprise all or part of the control system) may be included to enable fill or partial control of the photon source device 10A-10D and/or a control system of the invention. In embodiments, the PBMT system 200 may include an “over-ear” form factor 224, configured to both cover the ear and to be inserted into the ear canal of the subject (FIG. 7B); in such embodiments 200, an over-ear portion 224 may include an integral control feature 226, and may be configured for noise cancellation and/or acoustical acuity therapy using the photon source device(s) 10A-10D and/or another component of the PBMT system (FIG. 7B). In embodiments, the PBMT system 300 may include an “over-ear” form factor 324 with an external control feature 320 (FIG. 7C); in such embodiments, the over-ear portion 324 may include the photon source device(s) 10D operably connected to the computer system 302 via a wire connection 322. Selection of one or more particular embodiments may be driven by cost and/or design considerations.

[0198] In embodiments, the invention provides a method for photobiomodulation, comprising: evaluating a physiological state of a subject and compiling a first signature from data of the subject's profile, first evaluation, positioning a photon source device within and/or adjacent to the subject, activating the photon source device to deliver a safe and effective quantity of a therapeutic light to a portion of the subject, evaluating the physiological state of the subject and compiling a second signature from data of the second evaluation, and comparing the first signature with the second signature to determine change or the probability of change in the physiological state. The method may be performed by the control system and the photon source device, an individual such as a healthcare worker, the subject, or any combination thereof, regardless of whether the control system is local to the photon source device, remote to the photon source device, or both local and remote. The physiological state may correspond to a condition, disease, or disorder for which treatment with PBMT is being applied. For example, if PBMT is being used to treat SNHL, the physiological state may include hearing sensitivity, auditory acuity, medical history, or any combination thereof.

[0199] In embodiments, evaluation of the physiological state may be performed by the subject, an individual such as a healthcare worker, an authorized third party or any combination thereof. The physiological state may correspond to a condition, disease, and/or disorder for which treatment with PBMT is being applied. For example, if PBMT is being used to treat SNHL, the physiological state may include current hearing sensitivity, past auditory sensitivity, current auditory acuity, past auditory acuity, or any combination thereof. Additional physiological states which may be utilized by the present invention include, but are not limited to, physiological sensing (e.g. heart rate, heart rate variability, electro cardiogram, pulse wave velocity, blood flow, blood pressure, skin/tissue/core temperature, skin color, skin topology, pulse oximetry, tissue oximetry, tissue composition, tissue impedance, electroencephalogram, evoked potential voltages, galvanic skin response/skin conductance, body motion, body position, respiratory rate, respiratory volume, respiratory noise, VO.sub.2 max, algorithmically transformations of one or more of these physiological parameters into a different bioparameter), blood tests for stress and inflammatory biomarkers, genetic tests, microbiome tests, auditory tests, time since last PBMT treatment, number of previous PBMT treatments, last PBMT treatment dose energy e.g. J/cm.sup.2, and/or similar dose measurements, type of prior PBMT treatment, subject age, subject gender, subject ethnicity, and subject medical history (including but not necessarily limited to injuries such as punctured and/or ruptured tympanic membrane, procedures, prescriptions including current and prior prescriptions, presence of antibiotics or steroids or ototoxic compositions, audiometry including auditory acuity loss, range, and length of time since last PBMT treatment, co-morbidities, and the like). Additional data may also be included such as the amount of acoustical energy that the subject has been exposed to for a period of time.

[0200] In embodiments, the method may further comprise adjusting the quantity of the therapeutic light, adjusting a size of the portion of the subject's body which is illuminated/receives the therapeutic light, adjusting the sequence of therapeutic light applied, adjusting the pattern in which the therapeutic light is applied, or any combination thereof. The adjustment may be made by the control system, by the subject, by the individual such as the healthcare worker, or any combination thereof, regardless of whether the control system is local to the photon source device, remote to the photon source device, or both local and remote. In this manner, the treatment may be adjusted inside the medical setting and outside the medical setting as needed.

[0201] In embodiments, the method may further comprise administering one or more exogenous material and/or treatments to the subject. Exemplary exogenous materials include treatments such as localized and/or systemic therapies, including but not limited to pharmaceutical compositions, biological compositions, supplements, cell-based therapies, and other therapeutic services. In embodiments, the exogenous material may comprise a stem cell. A variety of factors may limit the effectiveness of stem cell therapy, and the method of the present invention may be used to overcome some or all of these factors to improve the safety and efficacy of a combined PBMT and stem cell therapy.

[0202] In embodiments, an output of the method of the invention includes recommendations for, and/or adjustments to, a dosing protocol adjustment for current and subsequent treatment applications (e.g., treatment duration, light frequency, light sequence, light intensity, and/or light pattern), which may be performed by a clinician, an audiologist, a patient, a care provider, or any combination thereof. The method may evaluate treatment efficacy and/or progress and escalate the intervention to a clinician if the subject is not achieving the requisite progress with the treatments on their own. The method may also output the results of sensor physiological and/or gains or losses in auditory sound frequency, intensity or degradation, recovery, and/or homeostasis. The auditory tests output may also determine the subject's ability to hear words and/or digits transmitted by the system. The method may output correlations between treatments, patient information, and auditory acuity by combining and evaluating data sets from one or more patients. In addition, the method may utilize artificial intelligence (AI) or machine learning (ML) analysis, which may include one or more of predicted future auditory acuity loss and/or restoration, risk profile and index of future auditory acuity loss and/or restoration, combine data from other subjects to increase accuracy of prediction and risk profile, combine data from other subjects to improve treatment profile such as duration, light wavelength, type (combination of photonic with other energy, supplements, drugs, foods, lifestyle, and the like), and any combination thereof.

[0203] In embodiments, the method of the control system may further comprise adjusting the quantity of the therapeutic light, wavelength, wavelength illumination sequence, wavelength illumination pattern, the area of the subject's body which receives the therapeutic light to optimize the PBMT, or any combination thereof. In embodiments, the quantity adjusted may include all wavelengths of the therapeutic light or a subset of wavelengths thereof. For example, if deeper penetration of tissue is needed, the wavelength of therapeutic light delivered to the portion of the subject may include a greater intensity of one or more longer wavelengths, optionally combined with a lesser intensity of shorter wavelengths. The sequence of light wavelengths emitting therapeutic light may be set to emit one or more wavelengths simultaneously, sequentially, in a graduated overlap, and/or in one or more patterns, or any combination of those elements. Similarly, if a greater portion of the subject needs to be irradiated with the safe and effective PBMT to facilitate treatment, then the optical properties of the photon source device may be adjusted to irradiate a larger area of the portion of the subject.

[0204] Combination Therapies

[0205] Generally, the present invention provides an improved localized PBMT therapy for the effective treatment and management of conditions, diseases, and disorders, which may be combined with any other known or unknown treatment, primary or secondary (adjunctive) treatment, localized or systemic treatment, or any combination thereof, whether intended for the same or a different condition, disease, or disorder. Exemplary therapies which may be combined with PBMT therapy of the present invention include, but are not limited to, biologic therapies, device therapies, drug therapies, gene therapies, service therapies, and supplement therapies.

[0206] Biologic Therapies

[0207] In embodiments, PBMT may be combined with one or more anti-apoptosis and/or anti-necrosis biologic therapeutics. As a non-limiting example, PBMT may be combined with a JNK inhibitor such as AM-111 (Sonsuvi®) or similar, XG-102 (brimapitide) or similar, or any combination thereof. In this manner, the therapeutic action of PBMT may benefit from or be enhanced by one or more anti-apoptosis and/or anti-necrosis biologic therapeutics.

[0208] In embodiments, PBMT may be combined with one or more antioxidant enzymatic scavenger biologic therapeutics. As a non-limiting example, PBMT may be combined with an anti-oxidant such as superoxide dismutase, catalase, glutathione peroxidases, thioredoxin peroxiredoxin, glutathione transferase, or any combination thereof. In this manner, the therapeutic action of PBMT may benefit from and/or be enhanced by one or more antioxidant enzymatic scavenger biologic therapeutics.

[0209] In embodiments, PBMT may be combined with one or more cell growth stimulating biologic therapeutics. As a non-limiting example, PBMT may be combined with a cell growth stimulator such as epidermal growth factor (EGF), a gamma secretase inhibitor, a WNT agonist, brain-derived neurotrophic factor (BDNF), an anti-NOTCH antibody, a composition comprising one or more progenitor and/or stem such as umbilical cord blood, a modulator of a stem cell signaling pathway such as one or more of Wnt, Notch, and Sonic Hedgehog, signaling pathways for development of hair cells from stem cells, one or more other exogenous factors which promote the expression of Math1 transcription factor, a composition comprising one or more mesenchymal stem cells (MSC), a composition comprising one or more pillar and/or Deiter cells, bone marrow, bone marrow-derived mesenchymal stem cells (MSCs), or any combination thereof. In this manner, the therapeutic action of PBMT may benefit from or be enhanced by one or more cell growth stimulating biologic therapeutics.

[0210] In embodiments, PBMT may be combined with one or more cell growth regulator biologic therapeutics. As a non-limiting example, PBMT may be combined with one or more bone remodeling modulators, such as sclerostin (bone growth modulator through Wnt inhibition). In this manner, the therapeutic action of PBMT may benefit from and/or be enhanced by one or more cell growth regulators.

[0211] In embodiments, PBMT may be combined with one or more cell growth stimulating biologic therapeutics. As a non-limiting example, PBMT may be combined with one or more LATS kinase compositions, stimulators, or inhibitors, such as one or more gene therapies which deliver, stimulate, or inhibit LATS kinase, or any combination thereof. In this manner, the therapeutic action of PBMT may benefit from and/or be enhanced by one or more cell growth stimulating biologic therapeutics.

[0212] In embodiments, PBMT may be combined with a biologic/drug combination for enhanced drug delivery. As a non-limiting example, PBMT may be combined with a therapeutic such as an auris pressure modulator, a combination of one or more of a immunomodulatory agent, an interferon, a channel modulator, a gamma-globulin, a chemotherapeutic agent, an anti-viral, an antibiotic, an anti-vascular agent, or any combination thereof. In embodiments, the biologic/drug combination may comprise a gamma secretase modulator and/or a pharmaceutically acceptable prodrug or salt thereof, and about 15% to about 35% by weight of a polyoxyethylene-polyoxypropylene triblock copolymer. In this manner, the therapeutic action of PBMT may benefit from and/or be enhanced by a biologic/drug combination for enhanced drug delivery.

[0213] Device Therapies

[0214] In embodiments, PBMT may be combined with one or more acoustical energy therapies. As a non-limiting example, PBMT may be combined with acoustical energy that downregulates and/or inhibits detrimental physiological changes that are associated with, correlated with, or causative of sensorineural auditory acuity (frequency and/or intensity) loss and/or tinnitus. In the alternative or in addition, PBMT may be combined with acoustical energy that upregulates and/or stimulates beneficial physiological changes that are associated with, correlated with, and/or causative of sensorineural hearing acuity (frequency and/or intensity) loss and/or tinnitus. In this manner, the therapeutic action of PBMT may benefit from and/or be enhanced by one or more acoustical energy therapies.

[0215] In embodiments, PBMT may be combined with one or more electromagnetic and/or electrical therapies. As a non-limiting example, PBMT may be combined with an electrical stimulation which promotes neural plasticity changes, such as an electrical therapy that downregulates and/or inhibits detrimental physiological changes that are associated with, correlated with, or causative of sensorineural auditory acuity (frequency and/or intensity) loss and/or tinnitus. In the alternative or in addition, PBMT may be combined with an electrical stimulation which promotes neural plasticity changes, such as an electrical therapy that upregulates and/or stimulates beneficial physiological changes that are associated with, correlated with, and/or causative of sensorineural auditory acuity (frequency and/or intensity) loss and/or tinnitus. In this manner, the therapeutic action of PBMT may benefit from and/or be enhanced by one or more electromagnetic or electrical therapies.

[0216] In embodiments, PBMT may be combined with one or more device therapies which enhance drug delivery. As a non-limiting example, PBMT may be combined with one or more therapies such as such as electrophoresis (opens pores to allow delivery of exogenous drugs, biologics, cellular treatments) which may be electrical or photonic, iontophoresis, reverse iontophoresis, or any combination thereof. In this manner, the therapeutic action of PBMT may benefit from and/or be enhanced by one or more device therapies which enhance drug delivery.

[0217] Drug Therapies

[0218] In embodiments, treatment with other drug therapies and/or exposure to ototoxic chemicals, metals and asphyxiants may cause hearing loss which requires treatment with PBMT of the present invention. As a non-limiting example, treatment with cytotoxic agents (e.g., antibiotics such as aminoglycosides), chemotherapeutic agents (e.g., carboplatin, cisplatin) may cause hearing loss. In addition, treatment with antibiotics (e.g., ciprofloxacin) and/or aminoglycosides (e.g., gentamicin, streptomycin), and ciprofloxacin may cause hearing loss. Accordingly, in embodiments, PBMT may be combined with one or more of these treatments to mitigate, prevent or treat hearing loss, SNHL, tinnitus, or ear ringing in a particular subject. Ototoxic chemicals may cause hearing loss such as: solvents e.g. carbon disulfide, n-hexane, toluene, p-xylene, ethylbenzene, n-propylbenzene, styrene and methylstyrene, trichloroethylene; asphyxiants e.g. carbon monoxide, hydrogen cyanide and its salts, tobacco smoke; nitriles e.g. 3-Butenenitrile, cis-2-pentenenitrile, acrylonitrile, cis-crotononitrile, 3,3′-iminodipropionitrile. Ototoxic metals and compounds may cause hearing loss e.g. mercury compounds, germanium dioxide, organic tin compounds, lead. Accordingly, in embodiments, PBMT may be combined with one or more other treatments defined herein to mitigate, prevent, restore and/or treat hearing loss, SNHL, tinnitus, or ear ringing in a subject caused by ototoxic chemicals.

[0219] In embodiments, PBMT may be combined with one or more anti-apoptotic or anti-inflammatory drug therapies. As a non-limiting example, PBMT may be combined with a therapeutic such as an inhibitor of BCL-2, an inhibitor of glycogen synthase kinase 3 (GSK3β), or any combination thereof. In this manner, the therapeutic action of PBMT may benefit from and/or be enhanced by one or more anti-apoptotic drug therapies.

[0220] In embodiments, PBMT may be combined with an anti-coagulant therapy. As anon-limiting example, PBMT may be combined with an anti-coagulant such as ancrod. In this manner, the therapeutic action of PBMT may benefit patients receiving an anti-coagulant therapy.

[0221] In embodiments, PBMT may be combined with one or more anti-inflammatory therapeutic drugs. As a non-limiting example, PBMT may be combined with one or more anti-inflammatory agents such as an antagonist of IL-1 receptor (e.g., anakinra), methotrexate, a therapy that increases adenosine signaling, a steroid (e.g., dexamethasone, corticosteroid, glucocorticoid, mineralocorticoid, anakinra), an anti-TNF-α agent, SPI-1005, Ebselen, or any combination thereof. In this manner, the therapeutic action of PBMT may benefit from and/or be enhanced by one or more anti-inflammatory therapeutic drugs.

[0222] In embodiments, PBMT may be combined with one or more anti-oxidant therapeutic drugs. As a non-limiting example, PBMT may be combined with an anti-oxidant such as sodium thiosulfate, EPI-743, vatiquinone, glutathione, a histone deacetylase inhibitor, a pan-HDAC inhibitor (e.g., SAHA), or any combination thereof. In this manner, the therapeutic action of PBMT may benefit from and/or be enhanced by one or more anti-oxidant therapeutic drugs.

[0223] In embodiments, PBMT may be combined with an anti-oxidant and/or free radical scavenger. As a non-limiting example, PBMT may be combined with a therapeutic such as HPN-07 (4-[(tert-butylimino)methyl] benzene-1, 3-disulfonate N-oxide) (disufenton sodium). In this manner, the therapeutic action of PBMT may benefit from and/or be enhanced by an anti-oxidant and/or free radical scavenger.

[0224] In embodiments, PBMT may be combined with an anti-viral agent. As a non-limiting example, PBMT may be combined with an anti-viral therapy such as valgancilovir, which is used to treat cytomegalovirus (CMV) infection which may lead to hearing loss. In this manner, the therapeutic action of PBMT may benefit patients receiving anti-viral therapy.

[0225] In embodiments, PBMT may be combined with a channel modulator drug therapeutic. As a non-limiting example, PBMT may be combined with a channel modulator such as such as AUT00063 or zonisamide. In this manner, the therapeutic action of PBMT may benefit from and/or be enhanced by a channel modulator drug therapeutic.

[0226] In embodiments, PBMT may be combined with a channel modulator or glutamate signaling drug therapeutic. As a non-limiting example, PBMT may be combined with a drug therapeutic such as gacyclidine, one or more N-methyl-D-aspartate (NMDA) receptor antagonists, or any combination thereof. In this manner, the therapeutic action of PBMT may benefit from and/or be enhanced by a channel modulator and/or glutamate signaling drug therapeutic.

[0227] In embodiments, PBMT may be combined with a channel modulator and/or neurotransmission modulator. As a non-limiting example, PBMT may be combined with a channel modulator and/or neurotransmission modulator drug therapeutic such as such as Zonisamide. In this manner, the therapeutic action of PBMT may benefit from or be enhanced by a channel modulator and/or neurotransmission modulator.

[0228] In embodiments, PBMT may be combined with one or more channel modulators and/or neurotrophic growth factors. As a non-limiting example, PBMT may be combined with a drug therapeutic such as a central nervous system (CNS) modulator, such as AUT00063, BDNF, or any combination thereof. In this manner, the therapeutic action of PBMT may benefit from and/or be enhanced by one or more channel modulators and/or neurotrophic growth factors.

[0229] In embodiments, PBMT may be combined with one or more neurotransmission modulators. As a non-limiting example, PBMT may be combined with a neurotransmission modulator such as PF-04958242 (α-amino-3-hydroxy-5-methyl-4—isoxazolepropionic acid potentiator), R-azasetron besylate (5-HT3 receptor antagonist and calcineurin inhibitor), vestipitant (NK1 receptor selective antagonist), or any combination thereof. In this manner, the therapeutic action of PBMT may benefit from and/or be enhanced by one or more neurotransmission modulators.

[0230] Gene Therapies

[0231] In embodiments, PBMT may be combined with one or more cell growth stimulator gene therapies. As a non-limiting example, PBMT may be combined with a cell growth stimulator drug gene therapy such as CGF166 (adenovirus vector containing cDNA for the human Atonal transcription factor (Hath1)), one or more AAV gene therapies (e.g., delivery of Atoh1, VGLUT3, or both), or any combination thereof (Atoh1 may also be referred to as Math1 (mouse) and/or HATH1 (human)). In this manner, the therapeutic action of PBMT may benefit from and/or be enhanced by one or more cell growth stimulator gene therapies.

[0232] In embodiments, PBMT may be combined with gene therapy containing any suitable gene for delivery which utilizes a particular vehicle for delivery. As a non-limiting example, PBMT may be combined with a therapy comprising a suitable gene therapy delivery vehicle such as AAV—i.e. which is an AAV viral vector with select peptides inserted to make it optimal for delivery into the inner ear. In this manner, the therapeutic action of PBMT may benefit from and/or be enhanced by gene therapy containing any suitable gene for delivery which utilizes a particular vehicle for delivery.

[0233] In embodiments, PBMT may be combined with one or more cell growth stimulator biologic and/or gene therapeutic approaches. As a non-limiting example, PBMT may be combined with cochlear hair cell regeneration therapy such as promoting ATOH1 expression, blocking NOTCH activity (e.g., using one or more gamma-secretase inhibitors), or any combination thereof. In this manner, the therapeutic action of PBMT may benefit from and/or be enhanced by one or more cell growth stimulator biologic and/or gene therapeutic approaches.

[0234] In embodiments, PBMT may be combined with one or more cell growth regulator gene therapies. As a non-limiting example, PBMT may be combined with a gene therapy such as delivery of p27Kip1, which must be tightly regulated to prevent overgrowth and/or lack of hair cell formation (both of which lead to hearing loss). In this manner, the therapeutic action of PBMT may benefit from and/or be enhanced by one or more cell growth regulator gene therapies.

[0235] Service Therapies

[0236] In embodiments, PBMT may be combined with one or more service therapies which benefit physiological, neural, and cognitive parameters of the subject. As a non-limiting example, PBMT may be combined with one or more service therapies such as acupuncture, cognitive behavior therapy, coping skills, physical activities, exercise, food, meditation, sleep treatments, stress treatments, yoga, stellate ganglion blocking (SGB), or any combination thereof. In this manner, the therapeutic action of PBMT may benefit from and/or be enhanced by one or more service therapies which benefit physiological, neural, and cognitive parameters of the subject.

[0237] Supplement Therapies

[0238] In embodiments, PBMT may be combined with one or more anti-oxidant and/or anti-inflammatory supplement therapies. As a non-limiting example, PBMT may be combined with one or more supplement therapies such as vitamin A (trans retinol 2), vitamin C(ascorbic acid), vitamin E (tocopherol and tocotrienols e.g., alpha tocopherol), beta carotene, glutathione, D-methionine, N-acetylcysteine, glutathione peroxidase mimicry (e.g., Ebselen), sodium thiosulfate, alpha lipoic acid, HPN-07 cofactor of mitochondrial enzymes, turmeric, a free radical scavenger, zinc gluconate, and any combination thereof. In this manner, the therapeutic action of PBMT may benefit from and/or be enhanced by one or more anti-oxidant and/or anti-inflammatory supplement therapies.

[0239] Assorted Therapies

[0240] Assorted therapies that may be combined with PBMT therapy include, but are but not limited to, treatment with one or more anti-inflammatory agents, treatment with one or more beneficial supplements, or any combination thereof.

[0241] In embodiments, the portion of the subject which receives PBMT may also comprise an exogenous material. Exemplary exogenous materials include treatments such as localized and/or systemic therapies, including but not limited to pharmaceutical compositions, biological compositions and/or cell-based therapies. In embodiments, the exogenous material may comprise a stem cell. A variety of factors may limit the effectiveness of stem cell therapy, and the PBMT system of the present invention may be used to overcome these factors to improve the effectiveness of stem cell therapy. In embodiments, PBMT may increase the stem cell efficacy by causing the stem cells to preferentially become hair cells by exposing the stem cells to a PBMT protocol that may include one or more light wavelengths and therapeutic emission sequences and patterns. In embodiments, PBMT may be combined with one or more intratympanic injections of one or more stem cells.

[0242] Additional assorted therapies that may be combined with PBMT include one or more anti-TNF-α agents, one or more auris pressure modulators, one or more CNS modulators, one or more cytotoxic agents, one or more anti-apoptotic agents, one or more bone-remodeling modulators, one or more free radical modulators, one or more ion channel modulators, one or more antibiotics (e.g., ciprofloxacin), one or more steroids (e.g., dexamethasone), one or more other compounds such as sodium thiosulfate, one or more other compounds such as gacyclidine, one or more other factors such as brain derived neurotropic factor (BDNF), one or more other factors such as gamma-secretase inhibitors, and any combination thereof.

[0243] Because human mesenchymal stem cells (MSCs) appear to require epidermal growth factor (EGF) and retinoic acid in culture for their directed differentiated into inner ear sensory cells, in embodiments having PBMT combined with one or more stem cell therapies, the treatment may also comprise use of one or more of epidermal growth factor (EGF), retinoic acid, and any combination thereof. In this manner, the therapy may facilitate differentiation of one or more MSCs into inner ear sensory cells for therapeutic benefit.

[0244] In embodiments, PBMT may be combined with the use of light, electricity, and/or acoustical energies in differing patterns and dosing methods to mitigate tinnitus and/or ear ringing and/or to modify the phantom signal generated by the brain which causes tinnitus and/or ear ringing. In embodiments, a treatment for tinnitus and/or ear ringing comprises administration of PBMT, optionally combined with one or more other stimulation therapies, such as electromagnetic, electrical, acoustic, or any combination thereof, wherein a signal of one or more of the PBMT, the electrical, photonic and/or acoustic therapies are adapted and/or changed over time to sustain an optimal safe and effective treatment of tinnitus and/or ear ringing. In embodiments, PBMT alone or in combination with one or more other therapies, stimulates a neurological response in the subject, which may comprise signal creation, neural remodeling, or any combination thereof to impart a therapeutic benefit to the subject.

[0245] Generally, PBMT of the present invention may be combined with any established, experimental, or alternative therapies that may be local or systemic in nature. In embodiments, one or more adjunctive therapies may be combined with PBMT of the present invention. Such adjunctive therapies may include, but may not necessarily be limited to, treatment with one or more lipoflavinoids, treatment with ketamine, treatment with MDMA, treatment with LSD, treatment with psilocybin, treatment with hypnosis, treatment with acupuncture, treatment with Ginkgo biloba, treatment with a B complex, and any combination thereof. In this manner, the PBMT of the present invention may be enhanced and/or complementary with respect to an adjunctive therapy, an established therapy, an experimental therapy, and/or an alternative therapy.

[0246] Variations of the invention—Variations of the invention are included within the scope of this invention and disclosure. Exemplary variations of the invention include, but are not limited to, the inclusion of one or more wavelengths of therapeutic light in the treatment method, which includes narrow band wavelengths, wide band wavelengths, or any combination thereof. While it may be beneficial to utilize primarily red and/or near-IR light, other wavelengths may also provide a therapeutic benefit, including but not necessarily limited to blue light, UV-A light, UV-B light, amber light, blue light, and green light. In embodiments, the photon source device may be configured to emit light having one or more wavelengths including, but not necessarily limited to: 447 nm, 532 nm, 635 nm, 808 nm, and any combination thereof.

[0247] In embodiments, the power source may be integral with the photon source device or non-integral with the photon source device, as a battery such as a rechargeable battery or as an external power source such as a larger battery or an alternating current (AC) or direct current (DC) external power source, or any combination thereof. The power of the therapeutic light may be adjustable such that irradiance and radiance, as well as the wavelength and/or wavelengths which are delivered to the portion of the subject receiving therapy, may be selectively adjustable to adjust and/or control the PBMT dosing provided. The photonic illumination plane may be selectively adjustable, or at a defined distance from the light source to the portion of the subject receiving PBMT, or any combination thereof. In addition, the photonic output may include biphasic pulses, monophasic pulses, multiphasic pulses, and any combination thereof. In embodiments, a single photonic source wavelength is provided by the light source, and this is converted into one or more different wavelengths through the use of one or more optics, one or more filters, one or more waveguides, one or more quantum dots (QD's), and any combination thereof. In an embodiment of the system it may be configured to prevent hearing injury from ototoxic drug and/or chemical exposure, age related degeneration, acoustical injury, viral/bacterial infection or any combination thereof. A preventative application could require the subject to be exposed to the PBMT for a period of time prior to exposure to such sources of hearing injury. This preventative treatment may utilize a specific wavelength of light, e.g. 808, 830, 650 nm, that has demonstrated protective capabilities for the subject, ambient environment and injury source.

[0248] In embodiments, the system provides local control system and data management, remote control system and data management, or a combination of all, as well as analytic features to determine the subject's therapy progress and adjust therapy during use of the invention. The invention may be configured to track patient compliance, status, and progress, and allow therapy variables to be adjusted remotely, for example, by a remotely located clinician. The system may upload sensor and therapy compliance and device status data to a remote data management and analysis system. In embodiments, sensor and treatment data that pertains to the invention may be reviewed remotely by the subject and/or authorized third parties, e.g., a clinician, In embodiments, the photon source device, the control system, and any combination thereof may include one or more wireless communication interfaces, which enables wireless control of one or more components of the system. In embodiments, the control system may upload data to a mobile device such as a smartphone, to a networked data management system, to a cloud-based data management and analytics system, or to another authorized data management system (e.g., such as a system containing protected health information, medical records, or employee records) or any combination thereof. In embodiments, the invention allows analysis and visual display of such results using a mobile device, a networked, cloud, and/or another data management system.

[0249] In embodiments, the invention provides a speculum that can be flexible, curved or straight, with a waveguide feature to illuminate the selected tissue region of the subject to deliver optimal safe and effective therapeutic light. The flexible and/or curved speculum may be utilized to mitigate ear canal topology for effective PBMT illumination of the targeted tissue region e.g. to the middle ear, cochlea and/or inner ear, for optimal hearing loss protection and/or restoration. In embodiments, the invention provides a standard or customized speculum cover that may be disposable or durable. In embodiments, the invention provides a speculum with a protective cover to protect the photon light source from foreign materials from impairing the operation of the device and may enable the adjustment of the optimal safe and effective light illumination to the selected site on the subject. This cover, which may be fixed or adjustable, may be configured with a known impact on the delivery of the photonic output and illumination site on the subject. Alternatively, or in addition, the invention provides one or more algorithms that adjust the system to limit the impact of the cover on the performance of the system. In embodiments, the invention may provide one or more algorithms for the system to create optimal safe and effective light signal that illuminates the selected tissue region of the subject. e.g. inner ear through the tympanic membrane, by adjusting one or more of the following device variables, e.g. irradiance, radiance, time of exposure, sequence, light wavelength, treatment frequency, distance to light source, state of the subject, light modulation, light coherence, site exposure, tissue type, prior treatments, etc. In embodiments, the invention provides a pre-treatment of the selected subject's site with exogenous materials or processes that improve the delivery of the optimal safe and effective therapeutic light signal to the selected site on the subject. Such pre-treatments may comprise the application of one or more reflective substances, materials or devices to the ear canal or within the oral cavity, and in this manner, the optimal safe and effective therapeutic light is able to travel to the selected treatment site with a known amount of signal loss/attenuation through absorption and reflectance into areas of the body adjacent and/or near the treatment site.

[0250] In embodiments, the photonic energy delivered to the portion of the subject's body may upregulate and/or stimulate beneficial physiological changes that are associated with, correlated with, and/or causative to mitigate sensorineural auditory acuity (frequency and/or intensity) loss, and/or tinnitus and/or ear ringing. In embodiments, the photonic energy delivered to the selected portion of the subject's body may down regulate and/or inhibit detrimental physiological changes that are associated with, correlated with, and/or causative of sensorineural auditory acuity (frequency and/or intensity) loss, and/or tinnitus and/or ear ringing. In embodiments, the photonic energy delivered to the portion of the subject's body may upregulate and/or stimulate beneficial physiological changes that are associated with, correlated with, and/or causative to mitigate sensorineural auditory acuity (frequency and/or intensity) loss, and/or tinnitus and/or ear ringing, and also down regulate and/or inhibit detrimental physiological changes that are associated with, correlated with, and/or causative of sensorineural auditory acuity (frequency and/or intensity) loss, and/or tinnitus and/or ear ringing.

[0251] In embodiments, the invention may utilize one or more waveguides (may be flexible, curved or straight) to deliver the therapeutic light to the selected portion of the subject's body. The flexible, straight and/or curved waveguide may be utilized to mitigate the ear canal curvature for effective delivery of PBMT to the middle ear and/or inner ear or any combination thereof. The invention may provide fine-tuned control over duty cycle, light wavelength, treatment frequency, sequence, pulse shape, therapy time, minimum to maximum light control, and/or increasing and decreasing power/energy for purposes of stimulating, inhibiting, and/or stimulating and inhibiting one or more biological responses in a single or multiple applications of the PBMT. In embodiments, the invention utilizes a vertical-cavity surface-emitting laser (VCSEL), which is a type of semiconductor laser diode with laser beam emission perpendicular from the top surface, which is contrary to conventional edge-emitting semiconductor lasers (also known as in-plane lasers). In embodiments of the invention, the invention stimulates one or more physiological responses, which may include one or more nerve cells.

[0252] In embodiments, the invention provides a mechanism that utilizes an external force (e.g. electromagnetic, e.g. near infrared light, X-ray, ultrasound, and the like) to change the activation state of one or more chemical and/or biological compounds to elicit a therapeutic outcome. In embodiments, the present invention may be utilized for wound healing therapy, for example, after tympanostomy tube insertion and/or removal, cochlear implant, post intratympanic injections and/or after tympanic membrane rupture. In this manner, the wound obtained from any of these procedures or injuries, e.g. tympanostomy tube insertion and/or removal, cochlear implant surgery, may be more effectively healed.

[0253] In embodiments, the invention provides systems, devices, and methods of utilizing PBMT to produce one or more biological responses in the subject. In embodiments, PBMT may generate one or more biological responses by varying stimulation sequence, irradiance, treatment time, patterns, duty cycle, sequence, wavelengths, location, and exposure area. In embodiments, PBMT of the present invention may stimulate and/or inhibit the cellular respiratory electron transport chain for optimal treatment based on a state of the subject. In embodiments, PBMT of the present invention may enable cellular REDOX regulation and related ROS and/or oxidative stress for optimal treatment based on a state of the subject. In embodiments, PBMT of the present invention may inhibit and/or stimulate cellular ATP for optimal treatment based on a state of the subject. In embodiments, PBMT of the present invention may manage cellular apoptosis and/or necrosis for optimal treatment based on a state of the subject. In embodiments, PBMT of the present invention may manage cellular nitric oxide (NO), cyclooxygenase (COX), and/or the interfacial water layer (IWL) responses for optimal treatment based on a state of the subject. In embodiments, PBMT of the present invention may upregulate messenger molecules, including but not necessarily limited to ROS and NO, which in turn may activate transcription factors such as NF-κB and AP-1, which may enter the nucleus and cause transcription of a range of new gene products for optimal treatment based on a state of the subject. In embodiments, PBMT of the present invention may mitigate, manage, or both mitigate and manage an underlying biological state of the subject to prevent further degradation of auditory acuity, hearing loss and associated side effects, e.g., tinnitus and/or ear ringing.

[0254] In embodiments, the PBMT systems, devices, and methods may deliver an optimal safe and effective light therapy to maintain a beneficial and/or therapeutic quantity of cellular compounds e.g. ATP, NO, ROS, in one or more cells, tissues, and/or biological structures of the subject. In embodiments, the optimal therapeutic light energy may be between 0.5 and 5.0 J/cm.sup.2 at the selected tissue site on the subject. In embodiments, the optimal therapeutic light energy at one or more selected tissue sites on the subject may be about 2.8 J/cm.sup.2 or exactly 2.8 J/cm.sup.2. The amount of therapeutic light energy delivered to one or more selected tissue sites will be based upon the needed physiological response, e.g. stimulation, inhibition or a combination of those responses. An example is therapeutic light may be delivered to a portion of a subject's body for maintenance or optimization of the cellular compounds e.g. ATP, NO, ROS, levels in one or more cells, tissues, or biological structures of the subject. In embodiments, the PBMT systems, devices, and methods may deliver an optimal safe and effective light energy to maximize the amount of cellular compounds, e.g. ATP, NO, ROS in one or more cells, tissues, and/or biological structures of the subject, by varying the time of treatment. In embodiments, the time of treatment may be between 15 and 30 minutes, depending on the amount of the cellular compounds, e.g. ATP, NO, ROS, that is desired to be produced from the PBMT stimulation.

[0255] In embodiments, the PBMT systems, devices, and methods may utilize one or more light wavelengths including, but not necessarily limited to: 447 nm, 532 nm, 635 nm, 808 nm, and any combination thereof. In embodiments, the one or more light wavelengths utilized may comprise one or more additional light wavelengths which may be adjacent to the utilized light wavelength. For example, to deliver a nominal wavelength, a range of wavelengths around the nominal wavelength may be included in the PBMT. As a non-limiting example, to deliver 447 nm light to a subject for PBMT, a range of wavelengths may be delivered, wherein 447 nm is within the range, e.g., 446 nm to 448 nm, 445 nm to 449 nm, and 444 nm to 450 nm. The range of wavelengths may be expressed as a nominal wavelength plus or minus a surrounding range of wavelengths, or may be expressed as a percentage of the nominal wavelength, or may be expressed as a range having a minimum and a maximum, as would be understood by a person having ordinary skill in the art. As a non-limiting example, to deliver 447 nm light to the subject for PBMT, light represented as 447±1 nm may be delivered. Similarly, to deliver 447 nm light to the subject for PBMT, light represented as 447±2 nm may be delivered.

[0256] In embodiments, therapeutic light of the PBMT of the present invention may comprise, may consist essentially of, or may consist of light with a nominal wavelength of 447 nm. In embodiments, the light may have a wavelength of 447±1 nm, 447±2 nm, 447±3 nm, 447±4 nm, 447±5 nm, or 447±10 nm or more. In this manner, in a sense, any range of wavelengths of light which includes 447 nm may be utilized in embodiments.

[0257] In embodiments, therapeutic light of the PBMT of the present invention may comprise, may consist essentially of, or may consist of light with a nominal wavelength of 532 nm. In embodiments, the light may have a wavelength of 532±1 nm, 532±2 nm, 532±3 nm, 532±4 nm, 532±5 nm, or 532±10 nm or more. In this manner, in a sense, any range of wavelengths of light which includes 532 nm may be utilized in embodiments.

[0258] In embodiments, therapeutic light of the PBMT of the present invention may comprise, may consist essentially of, or may consist of light with a nominal wavelength of 635 nm. In embodiments, the light may have a wavelength of 635±1 nm, 635±2 nm, 635±3 nm, 635±4 nm, 635±5 nm, or 635±10 nm or more. In this manner, in a sense, any range of wavelengths of light which includes 635 nm may be utilized in embodiments.

[0259] In embodiments, therapeutic light of the PBMT of the present invention may comprise, may consist essentially of, or may consist of light with a nominal wavelength of 808 nm. In embodiments, the light may have a wavelength of 808±1 nm, 808±2 nm, 808±3 nm, 808±4 nm, 808±5 nm, or 808±10 nm or more. In this manner, in a sense, any range of wavelengths of light which includes 808 nm may be utilized in embodiments.

[0260] In embodiments, the invention provides PBMT that includes two or more light wavelengths which are combined, sequential, overlapping, or any combination thereof. In embodiments, the PBMT includes a combination of all sequences in one or more illumination sequences. In embodiments, the PBMT utilized may depend on a treatment plan and may include one or more of a pre-treatment, a treatment, and/or a post-treatment, or any combination thereof. Each of these treatments may have the same or different purpose, e.g. protection, stimulation, inhibition or any combination thereof. In embodiments, the treatment method may vary one or more of the irradiance, the treatment time, the treatment wavelength, the treatment location, the treatment exposure area, and the treatment stimulation and/or inhibition illumination sequence or any combination thereof

[0261] Implementations

[0262] The operations, algorithms, and methods of the present invention may generally be implemented in suitable combinations of software, hardware, firmware, or a combination thereof, and the provided functionality may be grouped into a number of components, modules, and/or mechanisms. Modules can constitute either software modules (e.g., code embodied on a non-transitory machine-readable medium) or hardware-implemented modules. A hardware-implemented module is a tangible unit capable of performing certain operations and can be configured or arranged in a certain manner. In example embodiments, one or more computer systems (e.g., a standalone, client, or server computer system) or one or more processors can be configured by software (e.g., an application or application portion) as a hardware-implemented module that operates to perform certain operations as described herein.

[0263] In embodiments, a hardware-implemented module can be implemented mechanically or electronically. For example, a hardware-implemented module can comprise dedicated circuitry or logic that is permanently configured (e.g., as a special-purpose processor, such as a field programmable gate array (FPGA) or an application-specific integrated circuit (ASIC)) to perform certain operations. A hardware-implemented module can also comprise programmable logic or circuitry (e.g., as encompassed within a general-purpose processor or other programmable processor) that is temporarily configured by software to perform certain operations. It will be appreciated that the decision to implement a hardware-implemented module mechanically, in dedicated and permanently configured circuitry, or in temporarily configured circuitry (e.g., configured by software) can be driven by cost and time considerations.

[0264] Accordingly, the term “hardware-implemented module” should be understood to encompass a tangible entity, be that an entity that is physically constructed, permanently configured (e.g., hardwired), or temporarily or transitorily configured (e.g., programmed) to operate in a certain manner, to perform certain operations described herein, or both. Considering embodiments in which hardware-implemented modules are temporarily configured (e.g., programmed), each of the hardware-implemented modules need not be configured or instantiated at any one instance in time. For example, where the hardware-implemented modules comprise a general-purpose processor configured using software, the general-purpose processor can be configured as respective different hardware-implemented modules at different times. Software can accordingly configure a processor, for example, to constitute a particular hardware-implemented module at one instance of time and to constitute a different hardware-implemented module at a different instance of time.

[0265] Hardware-implemented modules can provide information to, and receive information from, other hardware-implemented modules. Accordingly, the described hardware-implemented modules can be regarded as being communicatively coupled. Where multiple such hardware-implemented modules exist contemporaneously, communications can be achieved through signal transmission (e.g., over appropriate circuits and buses that connect the hardware-implemented modules). In embodiments in which multiple hardware-implemented modules are configured or instantiated at different times, communications between such hardware-implemented modules can be achieved, for example, through the storage and retrieval of information in memory structures to which the multiple hardware-implemented modules have access. For example, one hardware-implemented module can perform an operation and store the output of that operation in a memory device to which it is communicatively coupled. A further hardware-implemented module can then, at a later time, access the memory device to retrieve and process the stored output. Hardware-implemented modules can also initiate communications with input or output devices, and can operate on a resource (e.g., a collection of information).

[0266] The various operations of example methods described herein can be performed, at least partially, by one or more processors that are temporarily configured (e.g., by software) or permanently configured to perform the relevant operations. Whether temporarily or permanently configured, such processors can constitute processor-implemented modules that operate to perform one or more operations or functions. The modules referred to herein can, in some example embodiments, comprise processor-implemented modules.

[0267] Similarly, the methods described herein can be at least partially processor-implemented. For example, at least some of the operations of a method can be performed by one of processors or processor-implemented modules. The performance of certain of the operations can be distributed among the one or more processors, not only residing within a single machine, but deployed across a number of machines. In embodiments, the processor or processors can be located in a single location (e.g., within an office environment, or a server farm), while in other embodiments the processors can be distributed across a number of locations.

[0268] The one or more processors can also operate to support performance of the relevant operations in a “cloud computing” environment or as a “software as a service” (SaaS). For example, at least some of the operations can be performed by a group of computers (as examples of machines including processors), these operations being accessible via a network (e.g., the Internet) and via one or more appropriate interfaces (e.g., application program interfaces (APIs)).

[0269] Example embodiments can be implemented in digital electronic circuitry, in computer hardware, firmware, or software, or in combinations thereof. Example embodiments can be implemented using a computer program product, e.g., a computer program tangibly embodied in an information carrier, e.g., in a machine-readable medium for execution by, or to control the operation of, data processing apparatus, e.g., a programmable processor, a computer, or multiple computers.

[0270] A computer program can be written in any form of description language, including compiled or interpreted languages, and it can be deployed in any form, including as a standalone program or as a module, subroutine, or other unit suitable for use in a computing environment. A computer program can be deployed to be executed on one computer or on multiple computers at one site or distributed across multiple sites and interconnected by a communication network.

[0271] In example embodiments, operations can be performed by one or more programmable processors executing a computer program to perform functions by operating on input data and generating output. Method operations can also be performed by, and apparatus of example embodiments can be implemented as, special purpose logic circuitry, e.g., an FPGA or an ASIC.

[0272] The computing system can include clients and servers. A client and server are generally remote from each other and typically interact through a communication network. The relationship of client and server arises by virtue of computer programs running on the respective computers and having a client-server relationship to each other. In embodiments deploying a programmable computing system, it will be appreciated that both hardware and software architectures merit consideration. Specifically, it will be appreciated that the choice of whether to implement certain functionality in permanently configured hardware (e.g., an ASIC), in temporarily configured hardware (e.g., a combination of software and a programmable processor), or a combination of permanently and temporarily configured hardware can be a design choice. Below are set out hardware (e.g., machine) and software architectures that can be deployed, in various example embodiments.

[0273] FIG. 8 depicts a schematic block diagram of the photobiomodulation computer system 400 bus architecture illustrating the numerous communications capabilities between the system bus 408 and the hardware elements integrated into the previously described photobiomodulation device 10A-10D.

[0274] Referring now to FIG. 8, which depicts a block diagram of a machine in the example form of a computer system 400 within which various instructions 424 may be executed to cause the machine to perform any one or more of the methodologies discussed herein. In alternative embodiments, the machine operates as a standalone device or can be connected (e.g., networked) to other machines. In a networked deployment, the machine can operate in the capacity of a server or a client machine in server-client network environment, or as a peer machine in a peer-to-peer (or distributed) network environment. The machine can be a personal computer (PC), a tablet PC, a set-top box (STB), a personal digital assistant (PDA), a cellular telephone, a web appliance, a network router, switch, or bridge, or any machine capable of executing instructions (sequential or otherwise) that specify actions to be taken by that machine. Further, while only a single machine is illustrated, the term “machine” shall also be taken to include any collection of machines that individually or jointly execute a set (or multiple sets) of instructions to perform any one or more of the methodologies discussed herein.

[0275] The example computer system 400 includes a processor 402 (e.g., a central processing unit (CPU), a graphics processing unit (GPU), or both), a main memory 404, and a static memory 406, which communicate with each other via a bus 408. The computer system 400 can further include a video display 410 (e.g., a liquid crystal display (LCD) or a cathode ray tube (CRT)). The computer system 400 also includes an alpha-numeric input device 412 (e.g., a keyboard or a touch-sensitive display screen), a user interface (UI) navigation (or cursor control) device 414 (e.g., a mouse), a disk drive unit 416, a signal generation device 418 (e.g., a speaker), and a network interface device 420.

[0276] The disk drive unit 416 includes a machine-readable medium 422 on which are stored one or more sets of data structures and instructions 424 (e.g., software) embodying or utilized by any one or more of the methodologies or functions described herein. The instructions 424 can also reside, completely or at least partially, within the main memory 404 or within the processor 402, or both, during execution thereof by the computer system 400, with the main memory 404 and the processor 402 also constituting machine-readable media.

[0277] While the machine-readable medium 422 is shown in an example embodiment to be a single medium, the term “machine-readable medium” can include a single medium or multiple media (e.g., a centralized or distributed database, and/or associated caches and servers) that store the one or more instructions 424 or data structures. The term “machine-readable medium” shall also be taken to include any tangible medium that is capable of storing, encoding, or carrying instructions 424 for execution by the machine and that cause the machine to perform any one or more of the methodologies of the present disclosure, or that is capable of storing, encoding, or carrying data structures utilized by or associated with such instructions 424. The term “machine-readable medium” shall accordingly be taken to include, but not be limited to, solid-state memories, and optical and magnetic media. Specific examples of machine-readable media 422 include non-volatile memory, including by way of example semiconductor memory devices, e.g., erasable programmable read-only memory (EPROM), electrically erasable programmable read-only memory (EEPROM), and flash memory devices; magnetic disks such as internal hard disks and removable disks; magneto-optical disks; and CD-ROM and DVD-ROM disks.

[0278] The instructions 424 can be transmitted or received over a communication network 426 using a transmission medium. The instructions 424 can be transmitted using the network interface device 420 and any one of a number of well-known transfer protocols (e.g., HTTP). Examples of communication networks include a local area network (LAN), a wide area network (WAN), the Internet, mobile telephone networks, plain old telephone (POTS) networks, and wireless data networks (e.g., Wi-Fi and WiMax networks). The term “transmission medium” shall be taken to include any intangible medium that is capable of storing, encoding, or carrying instructions 424 for execution by the machine, and includes digital or analog communications signals or other intangible media to facilitate communication of such software.

[0279] In embodiments, one or more components of the invention (e.g., the photon source device, the control system) may be configured for communication via radiofrequency (RF). In embodiments, the one or more components may send and/or receive data by transfer via RF to enable control of the device by another device. In additional embodiments, one or more components of the invention may be configured for communication via acoustic means, optical means, or both acoustic and optical means, and may include a microphone for receiving audio commands from a subject or individual, and/or may include a photosensor for receiving optical commands from the subject or individual. In embodiments, the one or more components of the invention may be configured for communication via RF, acoustic, and optical means, and in this manner the number of possible ways to control the invention may be increased or improved.

[0280] FIG. 9 depicts a schematic diagram of the various telecommunications 500 capabilities of the PBMT device, either alone or coupled to a smartphone utilizing a smartphone application (APP), or other like computing device. As shown, the PBMT device communicates wirelessly or by a connection wire to a smartphone APP and/or wirelessly directly to the internet/cloud. The smartphone/computing device is capable of communications directly to the internet/cloud or a local or remote data management system. Both the PBMT device and the smartphone/computing device communicate wirelessly to perform digital communications (talk, text and video) via the internet/cloud. The PBMT device and the smartphone/computing device communicate wirelessly to third party systems including providers, payors, employers and government agencies.

[0281] FIG. 10 depicts a flow chart illustrating the system architecture interrelationships between key elements of the system, including the human/biointerface, the therapeutic and diagnostic features and/or functions, adjunctive therapies and/or diagnostics, analytic capabilities, data management system, and the external data sets and inputs. The system's data management, algorithms and analytic capabilities can be located within the device, within a smartphone APP, within a local and/or remote data management system or combinations of each of these elements. The therapeutic and diagnostic algorithms can be updated manually or automatically with data collected from the subject, authorized third parties, devices, analytic system and/or from external sources, e.g. adjunctive therapies, adjunctive diagnostics, electronic health records, manual input by subject or authorized third party. The external data can be manually or automatically imported into the data management system, the smart phone APP, and/or device for use, analysis, storage or a combination of those purposes.

[0282] FIG. 11 depicts a flow chart illustrating the typical setup/authorization steps in which a subjects profile can be created by the subject or authorized third party with direct input, importation of external data or a combination of any of those methods. This sequence of steps may manually or automatically pair the assigned device(s), smart phone APP to the subject profile and records. After the creation of the subject profile, pairing of the device(s) and APPs the system may manually or automatically create the initial diagnostic and therapy protocols and transmit such protocols to the devices. The system may then authorize the devices to begin such diagnostic and therapeutic functions as defined in the protocols. The diagnostic and therapeutic protocols may be periodically manually or automatically updated with data from external sources and/or from the devices. The diagnostic and therapeutic protocols can include the scheduled time period in which they are performed.

[0283] FIG. 12 depicts a flow chart illustrating the use of the system in a hearing restoration and/or protection configuration having the diagnostic and therapeutic functions that are enabled after the system is setup as depicted in FIG. 11 and the devices properly inserted and/or affixed to the subject's body. The detection of proper insertion and/or affixing to the subject's body is determined by a sensing capability within the device and can be performed initially and periodically. The system may require a positive confirmation from the sensing feature that determines proper insertion/affixing to enable the therapeutic energy to be output from the device when it is initially inserted/affixed to subject and/or while in use. These data may be periodically transferred to the APP and/or data management system for analysis, display, storage and/or transfer to separate data management systems. As noted in FIG. 10 these features and functions may be within the device, adjacent APP, data management system or combinations of these configurations. The data management system and/or analytics may utilize the data generated by the system and/or external data imported during use to update the diagnostic and therapeutic protocols manually or automatically. The data management system and/or APP may enable review of the system data by the subject or authorized third parties, including but not limited to protocols, measured diagnostic sensing, and/or analyzed data sets. The data management system may enable alerts and/or notifications to the subject and/or authorized third parties to review data from one or more subjects and/or escalate care. Escalation of care can include manual or automated scheduling of appointments, digital communication messaging (text, phone calls, video calls), procedures, and adjunctive testing.

[0284] FIG. 13 depicts a flow chart illustrating the use of the system in a hearing restoration and/or protection configuration having the diagnostic and therapeutic functions that are enabled after the system is setup as depicted in FIG. 11 and the devices properly inserted and/or affixed to the subject's body. The detection of proper insertion and/or affixing to the subject's body is determined by a sensing capability within the device and can be performed initially and periodically. The system may require a positive confirmation from the sensing feature that determines proper insertion/affixing to enable the therapeutic energy to be output from the device when it is initially inserted/affixed to subject and/or while in use. The devices may periodically and/or continuously measure the subject's physiological bioparamenters and/or device performance/status with integrated sensing capabilities. These data may be periodically transferred to the APP and/or data management system for analysis, display, storage and/or transfer to separate data management systems. As noted in FIG. 10 these features and functions may be within the device, adjacent APP, data management system or combinations of these configurations. The data management system and/or analytics may utilize the data generated by the system and/or external data imported during use to update the diagnostic and therapeutic protocols manually or automatically. The data management system and/or APP may enable review by the subject or authorized third parties of the system data, including but not limited to protocols, measured diagnostic sensing, and analyzed data sets. The data management system may enable alerts and/or notifications to authorized third parties to review data from one or more subjects and/or escalate care. Escalation of care can include manual or automated scheduling of appointments, digital communication messaging (text, phone calls, video calls) procedures, and adjunctive testing.

[0285] The various embodiments of the Systems and Methods for Photobiomodulation primary elements will include as prominent configurations, design and operational functions:

[0286] Element 1—one or more light sources which are therapeutic energy adjusted for location on the subject for optimal therapy results.

[0287] Element 2—one or more light sources which are therapeutic energy adjusted from previously performed diagnostic test results data for optimal therapy results.

[0288] Element 3—one or more light sources in which therapeutic energy is adjusted when device location changes on the body during therapy.

[0289] Element 4—elements 1-3 above in varying combinations.

[0290] Element 5—elements 1-4 above light sources wavelengths are adjusted for optimal therapy results.

[0291] Element 6—elements 1-4 above wherein the light sources energy output is adjusted for optimal therapy results.

[0292] Element 7—elements 1-4 above wherein the area of body illuminated by light energy is adjusted for optimal therapy results.

[0293] Element 8—elements 5-7 above in varying combinations.

[0294] Element 9—elements 1-8 above with one or more of following diagnostic capabilities:

[0295] (a) Auditory Tests: evoke potential auditory brainstem response (ABR) and/or auditory steady-state response—ASSR, otoacoustic emissions (OAE), Pure-Tone, Speech Testing, Word tests e.g. Words in Noise, Digits in Noise, tests of the middle ear;

[0296] (b) Physiological: Temperature e.g. ear, skin, tissue, core, skin color, skin topology, tissue bioimpedance, galvanic skin response/skin conductance, electroencephalogram—EEG, evoked potential voltages, heart rate, heart rate variability, electro cardiogram, SpO2, StO2, blood pressure, pulse wave velocity, blood flow, respiration rate, respiratory volume, respiratory noise, VO.sub.2 max, tissue composition, motion, body position, ambient noise, otitis media, cerumen, optical and/or acoustic ear canal and tympanic membrane topography scans, 2D and/or 3D images and/or models, algorithmically transformations of one or more of these physiological parameters into a different bioparameter, and/or other electrical, optical or mechanical physiological measurements.

[0297] Element 10—elements 1-9 above with an advanced analytics capabilities system and/or device generated diagnostics and/or therapy data.

[0298] Element 11—elements 1-10 above with an advanced analytics capabilities system and/or device generated diagnostic and/or therapy data, and/or externally input data, and/or imported external data.

[0299] Element 12—elements 1-11 above analytic data output that adjusts diagnostic and therapeutic schedules based on prior analyzed data sets from subject and/or other subjects.

[0300] Element 13—elements 1-12 above analytic data output that adjusts therapeutic PBMT protocols based on prior analyzed data sets from subject and/or other subjects.

[0301] Element 14—elements 1-13 above data management system generated data for review by subject and/or authorized third party.

[0302] Element 15—elements 1-14 above combined with one or more other therapies such as:

[0303] (a) Exogenous chemicals e.g. pharmaceutical drugs, biologics, gene therapies e.g. stem cells, supplements;

[0304] (b) Devices—hearing aids, sound amplification; noise protection, communication devices, therapeutic devices;

[0305] (c) Services—Acupuncture, surgery, meditation, auditory training, brain plasticity remodeling training.

[0306] Element 16—elements 1-15 above fully integrated into one or more devices on the body—ear pod, headphone, noise protection, hearing-aid, personal sound amplification, communication devices.

[0307] Element 17—elements 1-15 above with system features and functions located on an on-body device and one or more adjacent computing devices, e.g. smartphone, computer, tablet or similar.

[0308] Element 18—elements 1-15 above with system features and functions located on an on-body device, and one or more adjacent computing devices, and one or more remote data management and analytic systems.

[0309] Element 19—elements 1-18 above with one or more data management and analytic systems that manually or automatically escalate subject care interventions utilizing data from current and/or prior diagnostic and therapy data analysis by one or more of the system analytic features. These interventions can be one or more of the following: Send one or more electronic/digital communication notifications (text, email, voicemail, etc.) to one or more authorized third parties for review and/or action; Automatically create a notification to review analyzed and historical data within data management system by one or more authorized third parties; Automatically scheduling an appointment and/or meeting with subject and authorized third party either in person or through other electronic/digital means, e.g. telemedicine, virtual presence, telephonic or televideo.

[0310] Element 20—elements 1-19 above with automated methods and features to enable manual or automated payment invoicing to authorized third parties for services provided, subscriptions and/or other goods and services, e.g. insurance, health savings accounts, credit/debit cards, employers, government agencies, individual service providers, etc.

[0311] Element 21—elements 1-19—above with automated methods and procedures to transfer data created, analyzed, imported and/or stored within data management system to authorized third parties.

[0312] In summary then, this application relates to systems, devices, and methods for diagnosing, preventing, and treating diseases and disorders through photobiomodulation therapy, either alone or in combination with one or more other therapies. More particularly, the present invention provides photon source devices configured to deliver light to a portion of an organism, which causes a physiological response within that light exposed organism. The invention also provides a system which includes one or more photon source devices and functionality for diagnosing or assessing a disease or disorder, and for monitoring responsiveness of the disease or disorder to treatment with the therapeutic light. Additionally, this application is directed to utilizing the present systems and devices in combination with known adjunctive therapies including devices, services, drugs, biologics, genetics and supplements to produce synergistic optimal therapeutic outcomes.

[0313] With respect to the above description then, it is to be realized that the optimum dimensional relationships for the parts of the Systems and Methods for Photobiomodulation, to include variations in size, materials, shape, form, function and manner of operation, assembly and use, are deemed readily apparent and obvious to one skilled in the art, and all equivalent relationships to those illustrated in the drawings and described in the specification are intended to be encompassed by the present design. Therefore, the foregoing is considered as illustrative only of the principles of the Systems and Methods for Photobiomodulation. Further, since numerous modifications and changes will readily occur to those skilled in the art, it is not desired to limit the Systems and Methods for Photobiomodulation to the exact construction and operation shown and described, and accordingly, all suitable modifications and equivalents may be resorted to falling within the scope of this application.

[0314] The Systems and Methods for Photobiomodulation 10A, 10B, 10C, 10D, 100, 200 and 300 shown in the drawings and described in detail herein disclose arrangements of elements of particular construction and configuration for illustrating preferred embodiments of structure and method of operation of the present application. It is to be understood, however, that elements of different construction and configuration and other arrangments thereof, other than those illustrated and described may be employed for providing the Systems and Methods for Photobiomodulation 10A, 10B, 10C, 10D, 10, 200 and 300 in accordance with the spirit of this disclosure, and such changes, alternations and modifications as would occur to those skilled in the art are considered to be within the scope of this design as broadly defined in the appended claims.

[0315] While certain embodiments of the inventions have been described, these embodiments have been presented by way of example only, and are not intended to limit the scope of the disclosure. Indeed, the novel methods and systems described herein may be embodied in a variety of other forms. Furthermore, various omissions, substitutions and changes in the systems and methods described herein may be made without departing from the spirit of the disclosure. For example, one portion of one of the embodiments described herein can be substituted for another portion in another embodiment described herein. The accompanying claims and their equivalents are intended to cover such forms or modifications as would fall within the scope and spirit of the disclosure. Accordingly, the scope of the present inventions is defined only by reference to the appended claims.

[0316] Features, materials, characteristics, or groups described in conjunction with a particular aspect, embodiment, or example are to be understood to be applicable to any other aspect, embodiment or example described in this section or elsewhere in this specification unless incompatible therewith. All of the features disclosed in this specification including any accompanying claims, abstract and drawings, and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive. The protection is not restricted to the details of any foregoing embodiments. The protection extends to any novel one, or any novel combination, of the features disclosed in this specification including any accompanying claims, abstract and drawings, or to any novel one, or any novel combination, of the steps of any method or process so disclosed.

[0317] Furthermore, certain features that are described in this disclosure in the context of separate implementations can also be implemented in combination in a single implementation. Conversely, various features that are described in the context of a single implementation can also be implemented in multiple implementations separately or in any suitable subcombination. Moreover, although features may be described above as acting in certain combinations, one or more features from a claimed combination can, in some cases, be excised from the combination, and the combination may be claimed as a subcombination or variation of a subcombination.

[0318] Moreover, while operations may be depicted in the drawings or described in the specification in a particular order, such operations need not be performed in the particular order shown or in sequential order, or that all operations be performed, to achieve desirable results. Other operations that are not depicted or described can be incorporated in the example methods and processes. For example, one or more additional operations can be performed before, after, simultaneously, or between any of the described operations. Further, the operations may be rearranged or reordered in other implementations. Those skilled in the art will appreciate that in some embodiments, the actual steps taken in the processes illustrated and/or disclosed may differ from those shown in the figures. Depending on the embodiment, certain of the steps described above may be removed, others may be added. Furthermore, the features and attributes of the specific embodiments disclosed above may be combined in different ways to form additional embodiments, all of which fall within the scope of the present disclosure. Also, the separation of various system components in the implementations described above should not be understood as requiring such separation in all implementations, and it should be understood that the described components and systems can generally be integrated together in a single product or packaged into multiple products.

[0319] For purposes of this disclosure, certain aspects, advantages, and novel features are described herein. Not necessarily all such advantages may be achieved in accordance with any particular embodiment. Thus, for example, those skilled in the art will recognize that the disclosure may be embodied or carried out in a manner that achieves one advantage or a group of advantages as taught herein without necessarily achieving other advantages as may be taught or suggested herein.

[0320] Conditional language, such as “can,” “could,” “might,” or “may,” unless specifically stated otherwise, or otherwise understood within the context as used, is generally intended to convey that certain embodiments include, while other embodiments do not include, certain features, elements, and/or steps. Thus, such conditional language is not generally intended to imply that features, elements, and/or steps are in any way required for one or more embodiments or that one or more embodiments necessarily include logic for deciding, with or without a subject input or prompting, whether these features, elements, and/or steps are included or are to be performed in any particular embodiment.

[0321] Conjunctive language such as the phrase “at least one of X, Y, and Z,” unless specifically stated otherwise, is otherwise understood with the context as used in general to convey that an item, term, etc. may be either X, Y, or Z. Thus, such conjunctive language is not generally intended to imply that certain embodiments require the presence of at least one of X, at least one of Y, and at least one of Z.

[0322] Language of degree used herein, such as the terms “approximately,” “about,” “generally,” and “substantially” as used herein represent a value, amount, or characteristic close to the stated value, amount, or characteristic that still performs a desired function or achieves a desired result. For example, the terms “approximately”, “about”, “generally,” and “substantially” may refer to an amount that is within less than 10% of, within less than 5% of, within less than 1% of, within less than 0.1% of, and within less than 0.01% of the stated amount. As another example, in certain embodiments, the terms “generally parallel” and “substantially parallel” refer to a value, amount, or characteristic that departs from exactly parallel by less than or equal to 15 degrees, 10 degrees, 5 degrees, 3 degrees, 1 degree, or 0.1 degree.

[0323] The scope of the present disclosure is not intended to be limited by the specific disclosures of preferred embodiments in this section or elsewhere in this specification, and may be defined by claims as presented in this section or elsewhere in this specification or as presented in the future. The language of the claims is to be interpreted broadly based on the language employed in the claims and not limited to the examples described in the present specification or during the prosecution of the application, which examples are to be construed as non-exclusive.

[0324] Further, the purpose of the foregoing abstract is to enable the U.S. Patent and Trademark Office, foreign patent offices worldwide and the public generally, and especially the scientists, engineers and practitioners in the art who are not familiar with patent or legal terms or phraseology, to determine quickly from a cursory inspection the nature and essence of the technical disclosure of the application. The abstract is neither intended to define the invention of the application, which is measured by the claims, nor is it intended to be limiting as to the scope of the invention in any way.