Nail-specific fungus treament

Abstract

The present disclosure relates to systems, devices, and methods for treating fungal infections in nails, nail beds, hyponychium, and / or at least one nail fold, using personalized components. In certain embodiments, the systems and devices clip onto a subject's appendage (having a nail and nail bed and nail folds) and energy from an antenna, via dielectric polarization, is converted into heat: i) at the subject's nail and / or nail bed and / or nail fold (providing a treatment temperature), and ii) at a personalized nail mirror mimic and nail bed mimic (providing a proxy temperature that is sensed). The sensed proxy temperature allows a personalized indication of an optimal treatment temperature, such that it can be adjusted to kill nail fungus (e.g., without severely burning a subject's appendage). In this regard, the personalized components of the systems and devices herein account for, or compensate for, differences in different subject's nail shapes, sizes, and topography.

Description

[0001] NAIL-SPECIFIC FUNGUS TREAMENT

[0002] The present application claims priority to U.S. Provisional application 63 / 621,746 filed January 17, 2024, which is herein incorporated by reference in its entirety.

[0003] FIELD OF THE INVENTION

[0004] The present disclosure relates to systems, devices, and methods for treating fungal infections in nails, nail beds, hyponychium, and / or at least one nail fold using personalized components. In certain embodiments, the systems and devices clip onto a subject's appendage (e.g., having a nail, nail bed, and nail folds) and energy from an antenna, via dielectric polarization, is converted into heat: i) at the subject's nail, nail bed and / or nail fold (providing a treatment temperature), and ii) at a personalized nail mirror mimic and nail bed mimic (providing a proxy temperature that is sensed). The sensed proxy temperature allows a personalized indication of an optimal treatment temperature, such that it can be adjusted to kill nail fungus (e.g., without severely burning a subject's appendage). In this regard, the personalized components of the systems and devices herein account for, or compensate for, differences in different subject's nail, and nail bed, shapes, sizes, and topography.

[0005] BACKGROUND OF THE INVENTION

[0006] Nail fungus, also known as onychomycosis or tinea unguium, is a common infection that often begins as a discolored spot under the tip of a fingernail or toenail. As the infection progresses, nail fungus causes the nail to discolor, thicken and crumble. Nail fungal infections are typically caused by a dermatophyte fungus. Yeasts and molds also can be responsible for nail fungal infections.

[0007] Signs of nail fungus include thickened, brittle, crumbly, or ragged nails that are distorted in shape and white or yellow in color. Infected nails also may separate from the nail bed, a condition called onycholysis. A severe case of nail fungus can be painful and may cause permanent damage to the nails. Nail fungus may lead to other serious infections that spread beyond the hands or feet, particularly for those with a suppressed immune system due to medication, diabetes or other conditions.

[0008] Risk factors for infection of the nail by fungus include having a family history of onychomycosis, having athlete’s foot, heavy perspiration, wearing footwear that hinders ventilation, living with someone that has nail fungus, being exposed to damp communal areas, and working in humid or moist environments. The risk of onychomycosis increases with increasing age and is more common in males than females. Other factors that predispose to nail fungal infection include having recent nail injury, psoriasis or other nail disorders, circulation problems, weakened immune system, or Down syndrome.

[0009] Existing treatments are highly unsatisfactory even though over a billion dollars a year is spent on oral and topical prescriptions. Oral antifungal drugs include terbinafine (LAMISIL) and itraconazole (SPORANOX). The drugs are typically taken for six to twelve weeks and results, if achieved, take months to observe. Treatment success rates with these drugs appeal' to be lower in adults over age 65. Importantly, oral antifungal drugs can cause serious side effects ranging from skin rash to liver damage. As such, these drugs may be contraindicated for patients with liver disease or congestive heart failure or those taking certain medications. Available topical treatments include medicated nail polishes (e.g., ciclopirox, aka PENLAC) and liquids (enilconazole, aka JUBLIA). The effectiveness of these treatments is limited.

[0010] Surgical, laser, and light-based approaches have also been used. Surgical approaches include nail removal. This is a painful procedure requiring weeks of dressing changes and management with pain medication. A new nail grows back very slowly (typically 12-18 months for a new big toenail) and may be permanently abnormal in shape and thickness. Laser and light approaches are newer and have not demonstrated effectiveness in curing nail fungus. They are also not available everywhere, are expensive, painful and typically not covered by insurance. People have also attempted home remedies, which have limited to no effectiveness. These include over-the-counter antifungal nail creams and ointments, use of VICKS VAPORUB, personal mechanical trimming or thinning of nails, use of snakeroot extract, and use of tea tree oil.

[0011] SUMMARY OF THE INVENTION

[0012] The present disclosure relates to systems, devices, and methods for treating fungal infections in nails, nail beds, hyponychium, and / or at least one nail fold (e.g., one or both lateral nail folds, and / or proximal nail fold) using personalized components. In certain embodiments, the systems and devices clip onto a subject's appendage (having a nail and nail bed and a nail fold) and energy from an antenna, via dielectric polarization, is converted into heat: i) at the subject's nail and nail bed and / or nail fold (providing a treatment temperature), and ii) at a personalized nail mirror mimic and nail bed mimic (providing a proxy temperature that is sensed). The sensed proxy temperature allows a personalized indication of the likely treatment temperature, such that it can be adjusted to kill nail fungus, such as T. rubrum, (e.g., without severely burning a subject's appendage). In this regard, the personalized components of the systems and devices herein account for, or compensate for, differences in different subject's nail, and nail bed, shapes, sizes, and topography.

[0013] In some embodiments, provided herein are systems and devices for treating fungus (e.g., T. rubrum) in a nail and / or nail bed and / or hyponychium, and / or nail fold (and / or nail matrix) comprising: a) an energy system for delivering energy to a nail and / or nail bed and / or at least one nail fold (and / or nail matrix) of an appendage of a subject such that heat is generated at the nail and / or nail bed and / or hyponychium, and / or nail fold (and / or nail matrix), optionally wherein said at least one nail fold is one or both lateral nail folds and / or a proximal nail fold; and b) at least one of the following: i) a nail bed mimic (NBM), and ii) a nail mirror mimic (NMM). In certain embodiments, the NMM has at least one (or two, or three, or four, or five) of the following properties: i) substantially matches at least one of the length, width, overall thickness, local thickness variations, nail arch, and nail surface topography, of the subject’s nail, ii) is not symmetrical along at least one of length, width, and thickness, and iii) in combination with the NBM, substantially replicates the subject's nail and nail bed (and / or nail matrix) with respect to heating therein caused by energy applied thereto. In particular embodiments, the energy system comprises an energy source and antenna. In other embodiments, the energy system further comprises at least one dielectric component.

[0014] In some embodiments, provided herein are systems and devices for treating fungus in a nail and / or nail bed and / or hyponychium, and / or nail fold (and / or nail matrix) comprising one or more or all of: a) a top applicator clip comprising a first surface; b) a bottom applicator clip comprising a second surface that receives the bottom of a subject's appendage that comprises a nail and nail bed and nail fold (and / or nail matrix); c) a shield component positioned below said first surface of said top applicator clip, wherein said shield component provides heat and electrometric shielding for said top applicator clip; d) a bottom treatment applicator (BTA) comprising a dielectric material, wherein said BTA is positioned above said nail and / or nail bed and / or hyponychium, and / or at least one nail fold (and / or nail matrix) when said subject's appendage is present, and wherein optionally said BTA substantially matches at least one of the length, width, or overall shape of said subject's nail and / or and / or hyponychium, nail bed and / or said at least one nail fold (and / or nail matrix), optionally wherein said at least one nail fold is one or both lateral nail folds and / or a proximal nail fold; c) one or more thermal sensors present in, or adjacent to, said BTA; and f) an antenna situated between said BTA and said heat shield, wherein said antenna emits energy towards said BTA when attached to an active energy source causing dielectric polarization of said BTA thereby heating said nail and said nail bed (and / or hyponychium, and / or nail matrix) and / or said at least one nail fold to a treatment temperature when said subject's appendage is present, optionally wherein said at least one nail fold is one or both lateral nail folds and / or a proximal nail fold.

[0015] In other embodiments, the systems and devices further comprise: a control component operably linked to said one or more thermal sensors in order to receive temperature measurements from said one or more thermal sensors, wherein said control component is configured to allow a user or computer algorithm to, in response to said temperature measurements, increase or decrease energy emitted by said antenna to increase or decrease said treatment temperature. In particular embodiments, the control component is configured to increase or decrease said treatment temperature to achieve an effective fungus treatment temperature. In particular embodiments, the shield component comprises: metal foil, metal tape, metal with an insulation barrier, or EMF absorbing fabric, and optionally wherein said metal is selected from copper, brass, nickel, silver, and tin.

[0016] In some embodiments, the devices, systems, and methods herein are used to treat all of, or most of, or one part of, the nail unit epithelium, which includes the nail bed, hyponychium, nail matrix, nail folds, hyponychium, and eponychium.

[0017] In particular embodiments, provided herein are methods of treating fungus (or suspected fungus, such as T. rubrum) in a nail and / or nail bed and / or nail fold (and / or hyponychium, and / or nail matrix) comprising: a) attaching a system or device to a subject's appendage that comprises a nail and a nail bed and nail fold (and / or hyponychium, and / or nail matrix), at least one of which has a fungal infection, or is suspected of developing a fungal infection, wherein the system or device comprises, or is operably linked, to an energy system, and wherein the system or device comprises a nail mirror mimic (NMM) customized to the subject's nail in at least one property, and optionally a nail bed mimic (NBM), and b) activating the energy system such that energy is delivered to the nail and / or nail bed and / or at least one nail fold (and / or hyponychium, and / or nail matrix) such that heat is generated at the nail and / or nail bed and / or nail fold (and / or hyponychium, and / or nail matrix), optionally wherein said at least one nail fold is one or both lateral nail folds and / or a proximal nail fold. In other embodiments, the methods further comprise: scanning the nail of the appendage of the subject with a scanning device to generate data, and employing the data to generate the NMM, and optionally, wherein the NMM substantially matches the width and / or length of the subject's nail. In additional embodiments, the methods further comprise: employing the data to generate a bottom treatment applicator (BTA) and / or top treatment applicator (TTA) which substantially match the width of the subject's nail. In additional embodiments, the at least one property is substantially matching the length, width, overall thickness, local spot thickness, shape, arch, or topography of the subject's nail. In some embodiments, the nail is treated at an early stage of fungal infection or prophylactically prior to infection. In some embodiments, the nail is treated at any various stage of infection, including severe infections where significant nail damage has already occurred.

[0018] In some embodiments, provided herein are methods comprising: a) attaching a system or device to a subject's appendage that comprises a nail and a nail bed and nail fold (and / or hyponychium, and / or nail matrix), at least one of which has a fungal infection or is suspected of developing a fungal infection, wherein the system or device comprises, or is operably linked, to an energy source which optionally comprises an antenna, and wherein the system or device comprises a nail mirror mimic (NMM) customized to the subject's nail in at least one property, and optionally a nail bed mimic (NBM), and wherein optionally the system or device is any one of systems or devices described herein, and b) activating the energy source such that: i) energy is delivered to the nail and / or nail bed and / or at least one nail fold (and / or hyponychium, and / or nail matrix) thereby heating the nail and / or nail bed and / or nail fold (and / or nail matrix) to a treatment temperature, optionally wherein said at least one nail fold is one or both lateral nail folds and / or a proximal nail fold, and / or ii) energy is delivered to the NMM and / or NBM thereby heating the NMM and / or NBM to a proxy temperature, and optionally wherein the systems and devices further comprise at least one temperature sensor that senses the proxy temperature. In additional embodiments, the at least one property is substantially matching the length, width, overall thickness, local spot thickness, shape, arch, or topography of the subject's nail and / or hyponychium, and / or at least one nail fold.

[0019] In particular embodiments, the system or device comprises, or is operably linked to, a control component, and wherein the methods further comprises: c) employing the control component, manually or automatically, to increase or decrease energy, optionally emitted by the antenna, to increase or decrease the treatment temperature. In further embodiments, the control component increases or decreases the treatment temperature to achieve an effective fungus treatment temperature that kills some, substantially, or all, of the fungal infection. In additional embodiments, the effective fungus treatment is such that it does not burn the subject's appendage. In some embodiments, the methods further comprise: c) applying protective drapes or gel around the subject's appendage. In other embodiments, the treatment temperature kills some, substantially all, or all, of the fungal infection. In certain embodiments, the BTA comprises a size and shape that substantially matches a margin extending beyond the sides of said nail that have fungus infected skin. In other embodiments, the BTA has a width that extends over said subject's nail and at least one nail fold, optionally wherein said at least one nail fold is one or both lateral nail folds and / or a proximal nail fold. In additional embodiments, the top treatment applicator (TTA) matches or substantially matches the width of the BTA (see, e.g., Figure 9A).

[0020] In certain embodiments, the fungal infection is an onychomycosis selected from: i) distal and lateral subungual onychomycosis, ii) superficial white onychomycosis, iii) proximal subungual onychomycosis, iv) complete dystrophic onychomycosis, v) non-dermatophyte mold and / or yeast onychomycosis, vi) mixed pattern onychomycosis, and vii) endonyx onychomycosis. In other embodiments, the subject's nail is a toenail that: i) is irregularly shaped, ii) is thicker than the same digit toenail in the general population, and / or iii) is excessively curved. In certain embodiments, the subject's nail is a fingernail that: i) is irregularly shaped, ii) is thicker than the same digit fingernail in the general population, and / or iii) is excessively curved. In particular embodiments, the subject is a human.

[0021] In some embodiments, the methods further comprise: scanning the nail of the appendage of the subject with a scanning device to generate data, and employing the data to generate the NMM, and optionally, wherein the NMM substantially matches the width and / or length of the subject's nail. In further embodiments, the methods further comprise: employing the data to generate a bottom treatment applicator (BTA) and / or top treatment applicator (TTA) which substantially match the width of the subject's nail and / or nail bed and / or at least one nail fold (e.g., one or both lateral nail folds and / or proximal nail fold). In other embodiments, the width of the BTA and TTA is the same or substantially the same.

[0022] In some embodiments, provided herein are methods comprising: a) scanning a nail of an appendage of a subject with a scanning device to generate data, b) processing the data with a computer system to generate a two-dimensional (2D) or three-dimensional (3D) computer image of the nail, wherein the computer system comprises non-transitory computer memory and a processor, wherein the non-transitory computer memory comprises software, c) further processing the 2D or 3D computer image of the nail with the software to generate a 2D or 3D computer mirror image of the nail. In particular embodiments, the methods further comprise: d) employing the 2D or 3D computer image of the nail to generate a physical nail mirror mimic (NMM). In additional embodiments, the NMM has at least one of the following properties: i) substantially matches at least one of the length, width, overall thickness, local thickness variations, nail arch, and nail surface topography, of the subject’s nail, ii) substantially replicates the size and / or shape of the subject's nail, and iii) is substantially a 2D or 3D mirror image reproduction of the subject’s nail.

[0023] In certain embodiments, a 3D printer is used to generate the physical NMM. In some embodiments, a mould is produced and used to generate the physical NMM. In some embodiments, the NMM is generated by machining. In some embodiments, the NMM comprises keratin or keratin-like material. In further embodiments, the NMM substantially matches at least two, three, or four of the length, width, overall thickness, local thickness variations, nail arch, and nail surface topography, of the subject’s nail. In some embodiments, the subject's appendage is a toenail or a finger nail. In other embodiments, the methods further comprise d) employing the 2D or 3D computer image of the nail to generate a bottom treatment applicator (BTA) as described herein, wherein the BTA comprises a surface that is shaped such that it substantially matches the curvature of the top of the subject's nail. In further embodiments, the methods further comprise assembling the physical NMM and / or the BTA into a nail fungal infection treatment device or system, optionally wherein the nail fungal infection treatment device or system comprises the other components recited above and herein. In further embodiments, the scanning device is selected from an ultrasound device, a MRI device, and a handheld object scanner (e.g., as shown in Figure 2).

[0024] In some embodiments, provided herein are systems and devices for treating (or preventing) fungus in a nail and / or nail bed and / or nail fold comprising: a) a top applicator clip comprising a first surface; b) a bottom applicator clip comprising a second surface that receives the bottom of a subject's appendage that comprises a nail and nail bed and nail fold, c) a nail bed mimic (NBM) positioned below the first surface of the top applicator clip, d) one or more thermal sensors present in, or adjacent to, the NBM, e) a nail mirror mimic (NMM) positioned below the NBM in a mirror image orientation with respect to the subjects nail when the appendage is present, wherein the NMM has at least one of the following properties: i) substantially matches at least one of the length, width, overall thickness, local thickness variations, nail arch, and nail surface topography, of the subject’s nail, ii) is not symmetrical along at least one of length, width, and thickness, and iii) in combination with the NBM, substantially replicates the subject's nail and nail bed with respect to heating therein caused by energy applied thereto; f) a top treatment applicator (TTA) positioned below the NMM and comprising a first dielectric material, g) a bottom treatment applicator (BTA) comprising a second dielectric material (e.g., the same or different as the first dielectric material), wherein the BTA is positioned above the nail when the subject's appendage is present; and h) an antenna situated between the BTA and the TTA, wherein the antenna emits energy towards the TTA and BTA when attached to an active energy source causing: i) dielectric polarization of the BTA thereby heating the nail and the nail bed and / or at least one nail fold to a treatment temperature when the subject's appendage is present, and ii) dielectric polarization of the TTA (e.g., which matched or substantially matches the width of the BTA) thereby heating the NMM and the NBM to a proxy temperature that is detected by the at least one or more thermal sensors (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10 or more). In certain embodiments, the dielectric polarization of said BTA further heats fungus infected skin areas around said nail (nail fold) to a treatment temperature when the subject's appendage is present.

[0025] In certain embodiments, the systems and devices further comprise: i) a control component operably linked to the one or more thermal sensors in order to receive proxy temperature measurements from the one or more thermal sensors, wherein the control component is configured to allow a user or computer algorithm (e.g., software) to, in response to the proxy temperature, increase or decrease energy emitted by the antenna to increase or decrease the treatment temperature. In other embodiments, the control component (e.g., handheld device or computer or smartphone or tablet computer) is configured to increase or decrease the treatment temperature to achieve an effective fungus treatment temperature. In additional embodiments, the effective fungus treatment temperature kills fungus but does not burn the subject's nail or nail bed or at least one nail fold (or at least both lateral nail folds and the proximal nail fold). In other embodiments, the NMM comprises keratin or keratin-like material.

[0026] In certain embodiments, the NMM substantially matches the length and / or width of the TTA and / or the BTA. In other embodiments, the NMM substantially matches at least two, three, or four of the length, width, overall thickness, local thickness variations, nail arch, and nail surface topography, of the subject’s nail. In some embodiments, the NMM is not symmetrical along at least one of length, width, and thickness, and optionally the NMM is not symmetrical along at least two or three of length, width, and thickness. In further embodiments, the NMM, in combination with the NBM, substantially replicates the subject's nail and / or nail bed with respect to heating therein caused by energy passing therethrough.

[0027] In further embodiments, the devices and systems further comprise the energy source (e.g., battery, rcscarchablc battery, wall outlet power, etc.), wherein optionally the energy source is a radio-frequency generator. In other embodiments, the energy source has an output power that ranges from 0 dBm to 43 dBm (ImW to 20W), and / or a frequency range from 0.01 GHz to 20 GHz, wherein optionally said frequency is about 8.4 GHz or about 8.0 GHz - 9.0 GHz (c.g., 8.0, 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8, 8.9, or 9.0 GHz).

[0028] In some embodiments, the second surface of the bottom applicator clip comprises a deformable pad (e.g., composed of cotton, gel, or a particular fabric). In certain embodiments, the deformable pad provides cooling to the appendage when present. In additional embodiments, the TTA is sized to substantially match the length and / or width of the nail mirror mimic. In other embodiments, the BTA is sized to substantially match the length and / or width of the nail. In particular embodiments, the NMM is substantially a three-dimensional mirror image reproduction of the subject’s nail.

[0029] In certain embodiments, the control component operably linked to the one or more thermal sensors is via wires or is wireless, and optionally, wherein the wireless comprises a Bluetooth connection (e.g., from a tablet computer, smartphone, or similar device) or near field communication connection. In other embodiments, the first surface of the top applicator clip comprises plastic (or fabric, gel, or cotton). In some embodiments, the NBM comprises nail bedlike material, which optionally comprises silicone, PDMS, or gel or other compatible material. In particular embodiments, the one or more thermal sensors comprises at least five or at least ten thermal sensors.

[0030] In certain embodiments, the systems and devices further comprises protective drapes or gel that is configured to surround the subject's appendage when present (e.g., as part of the device or added separately around the patient's appendage). In other embodiments, the BTA comprises a surface that is shaped such that it substantially matches the curvature of the top of a nail, and may further include the nail fold. In further embodiments, the TTA comprises a surface that is shaped such that it substantially matches the curvature of the NMM. In other embodiments, the subject's appendage is a toenail or a fingernail (e.g., from a human).

[0031] In particular embodiments, the first dielectric material of the TTA comprises silicone, Teflon, Kapton, FR-4, or polyethylene. In some embodiments, the second dielectric material of the BTA comprises silicone, Teflon, Kapton, FR-4, or polyethylene. In certain embodiments, the antenna comprises foil or a thin conductor composed of copper, aluminum, or gold-plated copper. In additional embodiments, the antenna is in a single- or multi-resonant slot (or double slot) or bowtie (or double bowtie) configuration on a dielectric substrate. In other embodiments, the antenna is a patch antenna. In other embodiments, the systems and devices further comprise a second, third, fourth, or fifth of the devices or systems described above or herein, and optionally such that the second, third, fourth, or fifth device or system is configured to treat a nail of a second, third, fourth, or fifth appendage of the subject. In additional embodiments, the systems further comprise a scanning system configured to scan the nail of the subject's appendage and generate a two- dimensional or three-dimensional computer image of the nail, and optionally further configured to generate a mirror image of the two-dimensional or three-dimensional computer image of the nail.

[0032] DESCRIPTION OF THE DRAWINGS

[0033] Figure 1A shows an exemplary nail and nail bed fungus treatment device or system. Figure IB shows an exemplary nail fungus treatment device or system clipped to a subject's toe, and a control and power cord operably connecting the device to an energy source and control component.

[0034] Figure 2 shows a workflow for generating customized nail mirror mimics and bottom treating applicators (e.g., by scanning a subject's toe), and integrating these components into a nail fungus treatment device.

[0035] Figure 3A shows various views of a subject's large nail and the customized nail fungus treatment device made to accommodate such nail (e.g., with a nail mirror mimic that matches at least the width of the large nail, and top and bottom treatment applicators that substantially match at least the width of the large nail). Figure 3B shows various views of a subject's small nail and the customized nail fungus treatment device made to accommodate such nail (e.g., with a nail mirror mimic that matches at least the width of the small nail, and top and bottom treatment applicators that substantially match at least the width of the small nail). Figure 3C shows various views of a subject's hypercurved (pincer) nail and the customized nail fungus treatment device made to accommodate such nail (e.g., with a nail mirror mimic that matches at least the width and arch of the hypcrcurvcd nail, and top and bottom treatment applicators that substantially match at least the width of the hypercurved nail). Figure 3D shows various views of a subject's shortened nail and the customized nail fungus treatment device made to accommodate such nail (e.g., with a nail mirror mimic that matches at least the shape of the shortened nail, and top and bottom treatment applicators that substantially match at least the width of the shortened nail). Figure 4A shows various views of a topographically distorted nail and the customized mirror mimic that is generated to accommodate the varying topography of this nail. Figure 4B shows various views of a front-indented nail and the customized nail mirror mimic that is generated to accommodate the indent in this nail.

[0036] Figure 5 shows an exemplary nail and nail bed fungus treatment device or system that includes an entry slot for introducing a custom nail mirror mimic that has standardized outer dimension to accommodate the slot.

[0037] Figure 6A shows a perspective view of an exemplary 3D image of a customized nail mimic generated from a scan of a subject's nail (shown prior to being converted into a mirror image). Figure 6B shows a side view of an exemplary 3D image of a customized nail mimic generated from a scan of a subject's nail (shown prior to being converted into a mirror image). Figure 6C shows a top view of an exemplary 3D image of a customized nail mimic generated from a scan of a subject's nail (shown prior to being converted into a mirror image).

[0038] Figure 7 shows an exemplary nail and nail bed fungus (and at least one nail fold) treatment device or system. In the exemplary treatment device or system of claim 7, a nail mirror mimic is not used for temperature sensing. Instead, temperature sensors are located near the nail itself. Temperature measurement of the nail bed is measured by interpreting the temperature from the sensors near the nail. In embodiments herein, such as Figure 7, where no nail mirror mimic is employed, the Bottom Treatment Applicator (BTA) size could be selected based on an 'off the shelf manner where, for example, small, medium, and large BTAs are ready to be used based on the size of the toenail being treated. In other embodiments like Figure 7 (where no nail mirror mimic is employed), the BTA could be custom designed (e.g., based on scanning the nail and / or taking a mould) for a particular patient's nail, particularly if the nail is an odd shape or complex.

[0039] Figure 8 shows an exemplary double bowtie antenna that can be used with the systems, devices, and methods herein.

[0040] Figure 9 A shows an exemplary nail, nail bed, and nail fold fungus treatment device or system that includes a Bottom Treatment Applicator that is wide enough (and / or long enough) to cover the subject's nail and at least one nail fold (e.g., one or both lateral nail folds and / or proximal nail fold), and further includes a Top Treatment Applicator with the same width (and / or length) as the Bottom Treatment applicator. Figure 9B shows an exemplary nail, nail bed fungus, and nail fold treatment device or system with a Bottom Treatment Applicator wide enough (and / or long enough) to cover the subject's nail and at least one nail fold (e.g., one or both lateral nail folds, and / or proximal nail fold).

[0041] DEFINITIONS

[0042] The terms “comprise(s),” “include(s),” “having,” “has,” “can,” “contain(s),” and variants thereof, as used herein, are intended to be open-ended transitional phrases, terms, or words that do not preclude the possibility of additional acts or structures. The singular forms “a,” “and” and “the” include plural references unless the context clearly dictates otherwise. The present disclosure also contemplates other embodiments “comprising,” “consisting of” and “consisting essentially of,” the embodiments or elements presented herein, whether explicitly set forth or not.

[0043] For the recitation of numeric ranges herein, each intervening number there between with the same degree of precision is explicitly contemplated. For example, for the range of 6-9, the numbers 7 and 8 are contemplated in addition to 6 and 9, and for the range 6.0-7.0, the number 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, and 7.0 are explicitly contemplated.

[0044] DETAILED DESCRIPTION OF THE INVENTION

[0045] The present disclosure relates to systems, devices, and methods for treating fungal infections in nails and nail bednail beds and at least one nail fold (e.g., one or both lateral nail folds and / or proximal nail fold) using personalized components. In certain embodiments, the systems and devices clip onto a subject's appendage (having a nail and nail bed and nail folds) and energy from an antenna, via dielectric polarization, is converted into heat: i) at the subject's nail and / or nail bed and / or nail fold (providing a treatment temperature), and ii) at a personalized nail mirror mimic and nail bed mimic (providing a proxy temperature that is sensed). The sensed proxy temperature allows a personalized indication of the likely treatment temperature, such that it can be adjusted to kill nail fungus (e.g., without severely burning a subject's appendage). In this regard, the personalized components of the systems and devices herein account for, or compensate for, differences in different subject's nail, and nail bed, shapes, sizes, and topography.

[0046] There are large variations in nail size, thickness and shape which occur with severe onychomycosis. The systems, devices, and methods herein address this variation. In certain embodiments, a nail is 2D scanned where, for example, the scan is from proximal to distal, and then lateral to medial (or vice versa). Other exemplary steps arc as follows. A nail is ultrasound scanned using a 3D ultrasound or other 3D or 2D imaging modality under consistent conditions - scan speed, resolution, etc. This results in scans that capture, for example, gaps under nails and steep curvatures that level out. In order to provide appropriate and consistent temperature monitoring and appropriate and consistent energy deposition, in some embodiments, the technology accounts for these nail-specific conditions in the custom components to provide a nail fungus treatment device or system. In some embodiments, using a 2D or 3D / Al algorithm, the ultrasound image is combined (top down + cross section, etc) and converted to a 2D, 3D, or other printer file type (in mirror fashion) and printed using materials matching or substantially close to the thermal and dielectric properties of keratin. The printed nail mirror mimic is utilized on the reflective (upward) side of the system and devices herein, such as shown in Figure 1A. In some embodiments, the 2D, 3D, or other type of nail file is also used to design a bottom treatment applicator to shield the skin next to the nail and prevent energy deposition (similar to an x-ray collimator however much more precise) from the adjacent skin. Additionally, in certain embodiments, such as in cases of high variation in thickness or extreme curvature, one can place a keratin like “even-up structure I substrate” on both the nail and the nail mimic to ensure even deposition on energy across nail. In some embodiments, the temperature sensors comprise optical thermocouples (e.g., Proximion FBG array temperature sensor). In some embodiments, thermocouples accurately and responsively sense temperature across fibers (e.g., 0.8mm fibers). In some embodiments, the system utilizes temperature sensors that comprise individual sensors or multi-point sensors in a single temperature sensing device component. In some embodiments, the temperature sensor comprises an infrared temperature sensor or camera.

[0047] In some embodiments, the variation in nail size and / or shape of a patient is accommodated by taking a mould impression of the nail and / or toe (e.g., similar what is done at a dentist office). This impression may be sent to the manufacturer to help build the custom systems and devices herein (e.g., instead of or in addition to the scanning used herein).

[0048] Figures 1-9 shows exemplary embodiments herein of the systems, devices, and construction methods. These figures are described in detail below.

[0049] Figure 1A shows an exemplary nail fungus treatment device or system. Figure IB shows an exemplary nail fungus treatment device or system clipped to a subject's toe, and a control and power cord operably connecting the device to an energy source and control component. Top and bottom applicator clips provide the outer components of the device, and can be configured, for example, with a spring-like hinge in order to clamp down on a subject's appendage. From top to bottom in Figure 1A, the following components of the device, and a subject's appendage, arc shown: i) a nail bed mimic (e.g., that substantially recapitulates the subject's nail bed), ii) temperature sensors that, for example, may be embedded in the nail bed mimic material; iii) nail bed mirror mimic that, for example, recapitulates in mirror fashion properties of the subject's nail to be treated, such as length, width, thickness, arch, and topography; iv) a top treatment applicator that, for example, is composed of dielectric materials and has substantially the same length and / or width of the subject's nail to be treated; v) an antenna that, for example, is configured to receive power from a power source and generate energy bi-directionally, where the antenna emits energy bi-directionally toward the nail and nail bed and simultaneously to the nail mirror mimic and the nail bed mirror mimic; vi) a bottom treatment applicator that, for example, is composed of dielectric material (e.g., the same as or different from the top treatment applicator), and has substantially the same length and / or width of the subject's nail to be treated; vii) a nail of an appendage of a subject that may have a fungus infection and has subject-specific properties, such as length, width, topography, arch, and other surface topography variability portions; viii) a nail bed under the nail of a subject, which may be have a fungal infection; ix) a toe or finger of the subject that carries the nail; and x) a bottom applicator clip, which may be padded to more comfortable accommodate the subject's appendage and / or provide cooling to counter the heat generated when the exemplary device is in use. Also shown on the side of the subject's appendage are protective drapes or gel that serve to keep portions of the subject's appendage from getting burned during treatment.

[0050] Figure 2 shows a workflow for generating customized nail mirror mimics and bottom treating applicators, and integrating these components into a nail fungus treatment device. Three different sized toes with distinct nails are shown to demonstrate how various components are customized. Initially, the subject's toe or toes are scanned, such as with a handheld scanner (e.g., intraoral scanner or other handheld scanners), or by ultrasound or similar modality. This scanning generates data which is analyzed and processed by a computer that comprises software that generates 2D or 3D images of the scanned nails. Software on the computer then provides a mirror image of the 2D or 3D images to generate nail mirror mimic data. This data can, for example, be sent to a device used to generate the physical nail mirror mimics and the bottom (and top) treatment applicators. Next, these personalized components are integrated into an exemplary nail fungus treatment device (e.g., where the device has a nail mirror mimic and / or bottom or top treatment application, that substantially matches the width, length, arch, or overall dimensions of the subject's nail).

[0051] Figure 3A shows various views of a subject's large nail and the customized nail fungus treatment device made to accommodate such nail (e.g., with a nail mirror mimic that matches at least the width of the large nail, and top and bottom treatment applicators that substantially match at least the width of the large nail). Matching the width (and length or other features) allows a maximization of the nail and nail bed treatment area, without, for example, over-heating the skin immediately next to the nail (nail fold skin) or the cuticle. For example, comparing the nails in Figures 3A and 3B, which are different in size, using non-customized components (such as a 'medium nail' size treatment device) in a nail fungus treatment device undesirably leaves large areas of the large nail untreated and may cause heat damage (e.g., severe burning) on the skinfold and cuticles of the small nail. Similarly, in Figures 3C, the nail has somewhat of an hourglass shape. Preparing nail mirror mimetics and top and bottom applicators that generally account for this shape provide personalize treatment (e.g., optimal treatment area, and lack of severe burning surround skin and cuticle) where the subject has such an irregularly shaped nail. The same applies to the shortened and topographically altered nail in Figure 3D, where customization of treatment components allows for a personalized, optimized treatment outcome.

[0052] Figure 4A shows various views of a topographically distorted nail and an exemplary customized mirror mimic that is generated to accommodate the varying topography of this nail. Figure 4B shows various views of a front-indented nail and a customized nail mirror mimic that is generated to accommodate the indent in this nail. The nail mirror mimics in these figures shows substantial customization. Such customization of the nail mirror mimic (e.g., in combination with the nail bed mimic) allows, for example, the temperature sensors to detect a proxy temperature (at a proximal end of the device away from the appendage) that closely matches the temperature being generated at the subject's nail and nail bed. In this regard, the proxy temperature allows one (e.g., manually or via a computer algorithm) to set and / or adjust the energy output to provide a treatment temperature that efficaciously treats or prevents a fungal infection, without causing undesired harm (e.g., severe burning) to surrounding anatomical structures.

[0053] Figure 5 shows an exemplary nail fungus treatment device or system that includes an entry slot for introducing a custom nail mirror mimic that has standardized outer dimension to accommodate the slot. For example, in certain embodiments, the nail mirror mimetics that are generated may all have the same exterior rectangular or square shape, and have the same outer dimension thickness, to allow them to easily insert into the slot shown in Figure 5. Such uniform dimensioned nail mirror mimics have internal shapes that are customized for a particular subject's nail (e.g., width, length, arch, thickness, topography, etc.). Figure 6A shows a perspective view of an exemplary 3D image of a customized nail mimic generated from a scan of a subject's nail (shown prior to being converted into a mirror image). Figure 6B shows a side view of an exemplary 3D image of a customized nail mimic generated from a scan of a subject's nail (shown prior to being converted into a mirror image). Figure 6C shows a top view of an exemplary 3D image of a customized nail mimic generated from a scan of a subject's nail (shown prior to being converted into a mirror image). 3D mirror images data is generated. Such 3D image data is sent to a device, such as a 3D printer, that synthesizes a physical version for insertion into the nail fungus treatment devices and systems described herein.

[0054] In some embodiments, the treated subject is a human. However, the systems, devices, and methods find use in veterinary application for treatment of companion animals (e.g., dogs, cats), livestock (e.g., including treatment of fungal infections in hooves or surrounding tissue, zoo animals, wild animals, and the like). Human subjects include both adults and children. Human may be selected based on risk factors, including but not limited to age, heavy perspiration, being male, family history, working in humid or moist environments, wearing footwear that hinders ventilation, living with someone that has nail fungus, exposure to damp communal areas, having athlete’s foot, having skin or nail injury, having psoriasis, circulation problems, weakened immune system, or Down syndrome.

[0055] The energy delivery herein provides a mechanism that is able to kill and / or inhibit the growth of a wide variety of organisms associated with nail fungus, onychomycosis, or related conditions. In some embodiments, the targeted organism is a dermatophyte (e.g., Trichophyton rubrum, T. interdigitale, Epidermophyton floccosum, T. violaceum, Microsporum gypseum, T. tonsurans, T. soudanense), Candida, or a nondermatophytic mold (Neoscytalidium, Scopulariopsis, and Aspergillus), or combinations thereof.

[0056] Treatment times and intervals may be selected based on the subject’s needs. In some embodiments, one treatment is provided. In some embodiments, two or more treatments are provided (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, . . ., 20, . . . chronic). Treatments may be spaced apart by minutes, hours, days, weeks, months, or years.

[0057] In some embodiments, the result of treatment is partial to complete clearance of infection (e.g., greater than 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 98%, 99% clearance or reduction as measured by any suitable assay, including but not limited to, culture, KOH prep, calcofluor white stain, molecular tests, antigen testing, nail surface appearance, nail lost regrowth, etc.). In some embodiments, there is minimal loss (e.g., no reversible loss) to no loss of healthy tissue, nail plate, or nail bed in response to the energy delivery.

[0058] In some embodiments, the energy delivery is combined with other existing therapies as a combination therapy. Such therapies include, but are not limited to, oral antifungal drugs (e.g., terbinafine, itraconazole), topical treatments (e.g., ciclopirox), mechanical treatments, and surgical and laser treatments.

[0059] Figure IB shows an energy source connected by a cable to the systems and devices herein. In some embodiments, the energy source is a radio-frequency (RF) generator (e.g., a micro wave generator). The energy source may comprise or consist of a tunable or fixed- frequency oscillator (either general-purpose laboratory-grade, e.g. from Keysight Technologies or Anritsu) or dedicated. Output powers from such oscillators may range, for example, from 0 dBm to 43 dBm (1 mW to 20W) or more, and frequency ranges may extend from 0.01 GHz to 20 GHz or more. Power from the oscillator may be amplified by a suitable solid-state power amplifier having gain of 1-45 dB or more and output power of +10 dBm to +43 dBm (e.g., 10 Watts) or more. The power amplifier may be a commercially-available module or a customized single- or multi-transistor module preferably located on or near to the applicator to minimize the effect of power losses in the delivery. In some embodiments, the cable is a coaxial cable. In some embodiments the cable is a plurality of cables either separate or bundled together or integrated (i.e., two functionalities in the same housing). In some embodiments, the cable provides a coolant channel to circulate coolant to the energy delivery device (e.g., antenna). In such embodiments, a coolant source (e.g., liquid coolant, gas such as CO2) is provided (not shown). In some embodiments, the cable further comprises a transmission line for transmitting data or other information to and from the energy delivery device to and from a control computer or component.

[0060] A connector may be used to connect the top applicator clip and the bottom applicator clips. Multiple connectors may be employed. The connector may include a spring or other tensioning component that causes the top applicator clip and bottom applicator clip to be directed towards one another by a force, such that the device clamps onto an object (e.g., finger, toe) inserted therebetween. Where such force is applied, the connector may employ any of a variety of mechanisms employing clips or clamps, including, but not limited to, tension / extension springs, compression springs, torsion springs, constant springs, variable springs, coil springs, flat springs, machined springs, serpentine springs, cantilevers, leaf springs, bands, band clamp, bar clamp, C-clamp, set screw, spring clamp, and the like. In certain embodiments, the antenna is preferably comprised of a foil or thin conductor (Cu, Al, Au-platcd Cu) formed in a single- or multi-resonant slot (or double slot) or bowtie (or double bowtie) configuration on a suitable dielectric substrate (e.g., silicone, Teflon, Kapton, FR-4, polyethylene). In other embodiments, the antenna comprises a patch antenna. However, other types of antennas such as dielectric antenna may also be employed. The conformal dielectric material, in some embodiments, may be a gel, silicone, PDMS, or other suitable material with low dielectric losses to maximize transfer of energy into the treatment zone.

[0061] Any suitable type or number of temperature sensors may be employed in the devices and systems herein. In some embodiments, a single sensor is employed. In some embodiments, two or more sensors are employed. The sensors may be wireless or wired and may employ any sensing mechanism. Contemplated sensors include, but are not limited to, thermistors, thermocouples, resistance thermometers, silicon bandgap temperature sensor, infrared monitors or cameras and the like. In some embodiments, sensors measure indirect consequences of temperature changes, such as pressure (e.g., pressure sensors) or displacement changes (e.g., due to swelling), for example, by assessing tension or displacement on a spring clip holding the treatment device onto a digit. In some embodiments, a reflectometer is employed. In some such embodiments, application of power is alternated between treatment and sensing of local dielectric properties of the treatment zone, enabling localized sensing of treatment progress (see e.g., Choi et al., Compact mixer-based 1-12 GHz reflectometer, in IEEE Microwave and Wireless Components Letters, vol. 15, no. 11, pp. 781-783, Nov. 2005, herein incorporated by reference in its entirety).

[0062] In some embodiments, a control component (e.g., computer, tablet computer, smartphone) is connected directly or wirelessly to the systems and devices herein and provides a user interface for the user to control the system. In some embodiments, the control features include, but are not limited to: selecting an energy level (and corresponding heat / temperature level) or treatment time; changing the treatment temperature based on the proxy temperature; selecting a pre-programmed energy del ivory protocol; collecting procedure data (temperature, energy levels); collecting or inputting patient-specific data (e.g., name, medical history, images of treatment area, insurance provider, payment code; etc.); setting safety protocols; selecting manual versus automatic settings; controlling coolant flow; turning the energy delivery device or generator or control computer on or off; and the like.

[0063] The temperature for killing of pathogens is selected based on the context of the desired treatment, including the nature of the subject being treated and the pathogen to be killed. In some embodiments, target tissue comprising a pathogen is heated to a temperature from 30°C to 70°C for a desired period of time (e.g., 40C to 60C; 45C to 55C; 50C to 55C; or any ranges or individual temperatures therein between; e.g., 40C, 41C, 42C, 43C, 44C, 45C, 46C, 47C, 48C, 49C, 50C, 51C, 52C, 53C, 54C, 55C, 56C, 57C, 58C, 59C, 60C, etc.).

[0064] The systems, devices and methods herein may be employed to treat various types of onychomycosis, such as those described below.

[0065] Distal subungual onychomycosis (DSO): This type of onychomycosis is the most common clinical presentation, in which the distal nail plate is separated from the nail bed. This infection is visualized as nails with normal surface texture and thickness but variable “bays” of white nail that extend from the distal nail tip proximally into the area of the nail bed. This form has been the cornerstone of antifungal drug studies. Since it generally does not involve the nail matrix, it is more amenable to improvement in clinical appearance than some other forms.

[0066] Proximal subungual onychomycosis (PSO): PSO is an uncommon form of onychomycosis that appears as a white discoloration below the nail plate at the base of the nail, near the lunula. The distal nail retains normal appearance and texture. PSO involves infection near the matrix, deep to the nail. It may be associated with trauma to the nail or to immune compromise. Therefore, the clinical presence of PSO may hint at an underlying medical disorder. In addition, PSO may reflect different species of fungus.

[0067] Superficial white onychomycosis (SWO): This form of onychomycosis is defined by the appearance of a white coating on the nail surface. This clinical form can be eliminated by filing or buffing the surface of the affected portion of the nail.

[0068] Complete dystrophy: Nails which are 100% dystrophic are manifested by yellowing and thickening of the entire nail unit. These nails may be difficult to treat due to irreversible damage to the nail matrix. In such cases even complete eradication of the fungus may not lead to normal nail growth rate or appearance.

[0069] In some embodiments, killing of toenail fungus (by the systems and devices herein) causses at least a 20% (e.g., 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, etc.) reduction viable fungi. Any suitable assay may be employed to measure organisms, including but not limited to, molecular techniques, culturing, and microscopy (see e.g., Paugam et al., J. Microbiol. Methods, 95(2):218-222 (2013), herein incorporated by reference in its entirety). REFERENCES

[0070] 1. U.S. Pat. 11,433,251

[0071] 2. Onycom Product web page: https: / / dermachom.com / products / onychom- antifungal-laser- device?agid=6445610042&helix_ad_id=17314633118 &helix_ad_id=17314633118 &utm _source=google&utm_medium=paid&utm_campaign=17314633118&utm_content=&utm_term =&gadid=&wbraid=Ck4KCQjwiIOmBhDPARI9AMasO3g6Qq5PkNDEGOAcgBjADWD- cvOJAIL9cMH2C-5kLHVS7sHBikfkWutmx_gxYgv5r_sfxa9KVLbJ3BoCmRM

[0072] 3. U.S. Patent Publication 2014 / 0200506

[0073] 4. US Patent 9,351,790

[0074] 5. US Patent Publication 2019 / 0321091

[0075] 6. US Patent Publication 2016 / 0113701

[0076] 7. US Patent 9,226,790

[0077] 8. PCT Application WO2012 / 106735

[0078] 9. PCT Application WO2015 / 100451

[0079] All publications and patents mentioned in the above specification are herein incorporated by reference. Various modifications and variations of the described compositions and methods of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention that are obvious to those skilled in the relevant fields are intended to be within the scope of the present invention.

Claims

CLAIMSWc claim:

1. A system or device comprising a nail mirror mimic (NMM) corresponding to a nail of a subject and an antenna configured to generate electromagnetic energy.

2. A system or device for treating fungus in a nail and / or nail bed and / or nail fold and / or hyponychium, comprising one or more or all of: a) a top applicator clip comprising a first surface; b) a bottom applicator clip comprising a second surface that receives the bottom of a subject's appendage that comprises a nail, nail bed, and a nail fold, c) a nail bed mimic (NBM) positioned below said first surface of said top applicator clip, d) one or more thermal sensors present in, or adjacent to, said NBM, e) a nail mirror mimic (NMM) positioned below said NBM in a mirror image orientation with respect to said subjects nail when said appendage is present, wherein said NMM has at least one of the following properties: i) substantially matches at least one of the length, width, overall thickness, local thickness variations, nail arch, and nail surface topography, of said subject’s nail, ii) is not symmetrical along at least one of length, width, and thickness, and iii) in combination with said NBM, substantially replicates said subject's nail and / or nail bed with respect to heating therein caused by energy applied thereto; f) a top treatment applicator (TTA) positioned below said NMM and comprising a first dielectric material, g) a bottom treatment applicator (BTA) comprising a second dielectric material, wherein said BTA is positioned above said nail and / or nail bed when said subject's appendage is present; and h) an antenna situated between said BTA and said TTA, wherein said antenna emits energy towards said TTA and BTA when attached to an active energy source causing: i) dielectric polarization of said BTA thereby heating said nail and said nail bed and / or said nail fold, to a treatment temperature when said subject's appendage is present, andii) dielectric polarization of said TTA thereby heating said NMM and said NBM to a proxy temperature that is detected by said at least one or more thermal sensors.

3. The system or device of claim 2, further comprising: i) a control component operably linked to said one or more thermal sensors in order to receive proxy temperature measurements from said one or more thermal sensors, wherein said control component is configured to allow a user or computer algorithm to, in response to said proxy temperature, increase or decrease energy emitted by said antenna to increase or decrease said treatment temperature.

4. The system or device of claim 3, wherein said control component is configured to increase or decrease said treatment temperature to achieve an effective fungus treatment temperature.

5. The system or device of claim 4, wherein said effective fungus treatment temperature kills fungus but does not severely burn said subject's nail or nail bed, or hyponychium, or nail folds; and / or wherein said dielectric polarization of said BTA further heats fungus infected skin areas comprising at least one nail fold, around said nail to a treatment temperature when said subject's appendage is present, optionally wherein said BTA has a width that extends over said subject's nail and said at least one nail fold, optionally wherein said at least one nail fold is one or both lateral nail folds and / or a proximal nail fold.

6. The system or device of claim 1 or 2, wherein said NMM comprises keratin or keratin- like material.

7. The system or device of claim 2, wherein said NMM substantially matches the length and / or width of said TTA and / or said BTA.

8. The system or device of claim 2, wherein said NMM substantially matches at least two, three, or four of the length, width, overall thickness, local thickness variations, nail arch, and nail surface topography, of said subject’s nail.

9. The system of device of claim 1 or 2, wherein said NMM is not symmetrical along at least one of length, width, and thickness, and optionally said NMM is not symmetrical along at least two or three of length, width, and thickness.

10. The system or device of claim 2, wherein said NMM, in combination with said NBM, substantially replicates said subject's nail and / or nail bed with respect to heating therein caused by energy passing therethrough.

11. The system of device of claim 1 or 2, further comprising said energy source, wherein optionally said energy source is a radio-frequency generator.

12. The system or device of claim 11, wherein said energy source has an output power that ranges from 0 dBm to 43 dBm (ImW to 20W), and / or a frequency range from 0.01 GHz to 20 GHz, wherein optionally said frequency range is about 8.4 GHz.

13. The system or device of claim 2, wherein said second surface of said bottom applicator clip comprises a deformable pad.

14. The system or device of claim 13, wherein said deformable pad provides cooling to said appendage when present.

15. The system or device of claim 2, wherein said TTA is sized to substantially match the length and / or width of said nail mirror mimic, and / or wherein said TTA is sized to match or substantially match the width of said BTA.

16. The system or device of claim 2, wherein said BTA is sized to substantially match the length and / or width of said nail and / or said nail bed, and / or wherein said BTA has a width and / or length that extends over said subject's nail and at least one nail fold, optionally wherein said at least one nail fold is one or both lateral nail folds and / or a proximal nail fold.

17. The system or device of claim 1 or 2, wherein said NMM is substantially a three- dimensional mirror image reproduction of said subject’s nail.

18. The system or device of claim 3, wherein said control component operably linked to said one or more thermal sensors is via wires or is wireless, and optionally, wherein said wireless comprises a Bluetooth connection or near field communication connection.

19. The system or device of claim 2, wherein said first surface of said top applicator clip comprises plastic.

20. The system or device of claim 2, wherein said NBM comprises nail bed-like material, which optionally comprises silicone, PDMS, or gel.

21. The system or device of claim 2, wherein said one or more thermal sensors comprises at least five or at least ten thermal sensors.

22. The system or device of claim 1 or 2, further comprises protective drapes or gel that is configured to surround said subject's appendage when present.

23. The system or device of claim 2, wherein said BTA comprises a surface that is shaped such that it substantially matches the curvature of the top of a nail, or wherein said BTA comprises a size and shape that substantially matches a margin extending beyond the sides of said nail that have fungus infected skin comprising at least one nail fold, optionally wherein said at least one nail fold is one or both lateral nail folds and / or a proximal nail fold..

24. The system or device of claim 2, wherein said TTA comprises a surface that is shaped such that it substantially matches the curvature of the NMM.

25. The system or device of claim 2, wherein said subject's appendage is a toenail or a fingernail.

26. The system or device of claim 2, wherein said first dielectric material of said TTA comprises silicone, Teflon, Kapton, FR-4, or polyethylene.

27. The system or device of claim 2, wherein said second dielectric material of said BTA comprises silicone, Teflon, Kapton, FR-4, or polyethylene.

28. The system or device of claim 2, wherein said antenna comprises foil or a thin conductor composed of copper, aluminum, or gold-plated copper.

29. The system or device of claim 2, wherein said antenna is in a single- or multi-resonant slot, double slot, bowtie, or double-bowtie configuration on a dielectric substrate, or wherein the antenna comprises a patch antenna.

30. The system or device of claim 1 or 2, further comprising a second, third, fourth, or fifth of said device or system of claim 1 or 2, and optionally such that said second, third, fourth, or fifth device or system is configured to treat a nail of a second, third, fourth, or fifth appendage of said subject.

31. The system of claim 1 or 2, further comprising a scanning system configured to scan said nail of said subject's appendage and generate a two-dimensional or three-dimensional computer image of said nail, and optionally further configured to generate a mirror image of said two- dimensional or three-dimensional computer image of said nail.

32. A method comprising: administering energy from a system or device of any of claims 1- 31 to a subject.

33. The method of claim 32, wherein said subject has a nail and / or nail bed and / or nail fold fungal infection.

34. A method comprising: a) attaching a system or device to a subject's appendage that comprises a nail, a nail bed, and a nail fold, at least one of which has a fungal infection or is suspected of developing a fungal infection, wherein said system or device comprises, or is operably linked, to an energy source which optionally comprises an antenna, and wherein said system or device comprises a nail mirror mimic (NMM) customized to the subject's nail in at least one property, and optionally a nail bed mimic (NBM) customized to thesubject's nail bed in at least one property, and wherein optionally said system or device is any one of claims 1-31, and b) activating said energy source such that: i) energy is delivered to said nail and / or nail bed and / or at least one nail fold thereby heating said nail and / or nail bed and / or hyponychium, and / or said at least one nail fold to a treatment temperature, and / or ii) energy is delivered to said NMM and / or NBM thereby heating said NMM and / or NBM to a proxy temperature, and optionally wherein said systems and devices further comprise at least one temperature sensor that senses said proxy temperature, optionally wherein said at least one nail fold is one or both lateral nail folds and / or a proximal nail fold.

35. The method of claim 34, wherein said system or device comprises, or is operably linked to, a control component, and wherein the methods further comprises: c) employing said control component, manually or automatically, to increase or decrease energy, optionally emitted by said antenna, to increase or decrease said treatment temperature.

36. The method of claim 35, wherein said control component increases or decreases said treatment temperature to achieve an effective fungus treatment temperature that kills some, substantially, or all, of said fungal infection.

37. The method of claim 36, wherein said effective fungus treatment is such that it does not severely burn said subject's appendage.

38. The method of claim 34, further comprising: c) applying protective drapes or gel around said subject's appendage.

39. The method of claim 34, wherein said treatment temperature kills some, substantially, or all, of said fungal infection.

40. The method of claim 33 or 34, wherein said fungal infection is an onychomycosis selected from: i) distal and lateral subungual onychomycosis, ii) superficial whiteonychomycosis, iii) proximal subungual onychomycosis, iv) complete dystrophic onychomycosis, v) non-dcrmatophytc mold and / or yeast onychomycosis, vi) mixed pattern onychomycosis, and vii) endonyx onychomycosis.

41. The method of claim 34, wherein said subject's nail is a toenail that: i) is irregularly shaped, ii) is thicker than the same digit toenail in the general population, and / or iii) is excessively curved.

42. The method of claim 34, wherein said subject's nail is a fingernail that: i) is irregularly shaped, ii) is thicker than the same digit fingernail in the general population, and / or iii) is excessively curved.

43. The method of claim 32 or 34, wherein said subject is a human.

44. The method of claim 34, further comprising: scanning said nail of said appendage of said subject with a scanning device to generate data, and employing said data to generate said NMM, and optionally, wherein said NMM substantially matches the width of said subject's nail.

45. The method of claim 44, further comprising: employing said data to generate a bottom treatment applicator (BTA) and / or top treatment applicator (TTA) which substantially match the width and / or length of said subject's nail and / or said subject's nail bed and / or at least one nail fold, optionally wherein said at least one nail fold is one or both lateral nail folds and / or a proximal nail fold.

46. A method comprising: a) scanning a nail of an appendage of a subject with a scanning device to generate data, b) processing said data with a computer system to generate a two-dimensional (2D) or three-dimensional (3D) computer image of said nail, wherein said computer system comprises non-transitory computer memory and a processor, wherein said non-transitory computer memory comprises software, and c) further processing said 2D or 3D computer image of said nail with said software to generate a 2D or 3D computer mirror image of said nail.

47. The method of claim 46, further comprising d) generating a physical nail mirror mimic (NMM) employing said 2D or 3D computer image.

48. The method of claim 47, wherein said NMM has at least one of the following properties: i) substantially matches at least one of the length, width, overall thickness, local thickness variations, nail arch, and nail surface topography, of said subject’s nail, ii) substantially replicates the size and / or shape of said subject's nail, and iii) is substantially a 2D or 3D mirror image reproduction of said subject’s nail.

49. The method of claim 47, wherein a 3D printer is used to generate said physical NMM.

50. The method of claim 47, wherein said NMM comprises keratin or keratin-like material.

51. The method of claim 47, wherein said NMM substantially matches at least two, three, or four of the length, width, overall thickness, local thickness variations, nail arch, and nail surface topography, of said subject’s nail.

52. The method of claim 47, wherein said subject's appendage is a toenail or a finger nail.

53. The method of claim 46 or 47, further comprising d) employing said 2D or 3D computer image of said nail to generate a bottom treatment applicator (BTA) as recited in claim 1, wherein said BTA comprises a surface that is shaped such that it substantially matches the curvature of the top of said subject's nail.

54. The method of claim 47 or 53, further comprising assembling said physical NMM and / or said BTA into nail fungal infection treatment device or system, optionally wherein said nail fungal infection treatment device or system comprises the other components recited in claim 1.

55. The method of claim 46, wherein said scanning device is selected from an ultrasound device, a MRI, device, and an handheld object scanner.

56. A system or device for treating fungus in a nail and / or nail bed comprising: a) an energy system for delivering energy to a nail and / or nail bed and / or hyponychium and / or at least one nail fold of an appendage of a subject such that heat is generated at said nail and / or nail bed and / or said at least one nail fold; and b) at least one of the following: i) a nail bed mimic (NBM), and ii) a nail mirror mimic (NMM), optionally wherein said at least one nail fold is one or both lateral nail folds and / or a proximal nail fold.

57. The system or device of claim 56, wherein said NMM has at least one of the following properties: i) substantially matches at least one of the length, width, overall thickness, local thickness variations, nail arch, and nail surface topography, of said subject’s nail, ii) is not symmetrical along at least one of length, width, and thickness, and iii) in combination with said NBM, substantially replicates said subject's nail and nail bed with respect to heating therein caused by energy applied thereto.

58. The system or device of claim 56, wherein said energy system comprises an energy source and antenna.

59. The system or device of claim 58, wherein said energy system further comprises at least one dielectric component.

60. A method of treating fungus in a nail and / or nail bed and / or nail fold comprising: a) attaching a system or device to a subject's appendage that comprises a nail and a nail bed and a nail fold and optionally a hyponychium, at least one of which has a fungal infection, or is suspected of developing a fungal infection, wherein said system or device comprises, or is operably linked, to an energy system, andwherein said system or device comprises a nail mirror mimic (NMM) customized to said subject's nail in at least one property, and optionally a nail bed mimic (NBM), and b) activating said energy system such that energy is delivered to said nail and / or nail bed and / or at least one nail fold such that heat is generated at said nail and / or nail bed and / or nail fold, optionally wherein said at least one nail fold is one or both lateral nail folds and / or a proximal nail fold.

61. The method of claim 60, further comprising: scanning said nail of said appendage of said subject with a scanning device to generate data, and employing said data to generate said NMM, and optionally, wherein said NMM substantially matches the width of said subject's nail.

62. The method of claim 61, further comprising: employing said data to generate a bottom treatment applicator (BTA) and / or top treatment applicator (TTA) which substantially match the width of said subject's nail.

63. The method of claim 60, wherein said at least one property is substantially matching the length, width, overall thickness, local spot thickness, shape, arch, or topography of said subject's nail.

64. A system or device for treating fungus in a nail and / or nail bed and / or hyponychium and / or nail fold comprising one or more or all of: a) a top applicator clip comprising a first surface; b) a bottom applicator clip comprising a second surface that receives the bottom of a subject's appendage that comprises a nail and nail bed and nail fold; c) a shield component positioned below said first surface of said top applicator clip, wherein said shield component provides heat and electrometric shielding for said top applicator clip; d) a bottom treatment applicator (BTA) comprising a dielectric material, wherein said BTA is positioned above said nail and / or nail bed and / or nail fold when said subject's appendage is present, and wherein optionally: i) said BTA substantially matches at least one of the length, width, or overall shape of said subject's nail and / or nail bed, and / orii) said BTA has a width and / or length that extends over said subject's nail and at least one nail fold, optionally wherein said at least one nail fold is one or both lateral nail folds and / or a proximal nail fold; e) one or more thermal sensors present in, or adjacent to, said BTA; and f) an antenna situated between said BTA and said heat shield, wherein said antenna emits energy towards said BTA when attached to an active energy source causing dielectric polarization of said BTA thereby heating said nail and said nail bed and / or hyponychium and / or said at least one nail fold to a treatment temperature when said subject's appendage is present.

65. The system or device of claim 64, further comprising: i) a control component operably linked to said one or more thermal sensors in order to receive temperature measurements from said one or more thermal sensors, wherein said control component is configured to allow a user or computer algorithm to, in response to said temperature measurements, increase or decrease energy emitted by said antenna to increase or decrease said treatment temperature.

66. The system or device of claim 65, wherein said control component is configured to increase or decrease said treatment temperature to achieve an effective fungus treatment temperature.

67. The system or device of claim 66, wherein said effective fungus treatment temperature kills fungus but does not severely burn said subject's nail or nail bed and / or said at least one nail fold.

68. The system or device of claim 66, wherein said dielectric polarization of said BTA further heats fungus infected skin areas around said nail, called said at least one nail fold, to a treatment temperature when said subject's appendage is present.

69. The system of device of claim 64, further comprising said energy source, wherein optionally said energy source is a radio-frequency generator.

70. The system or device of claim 69, wherein said energy source has an output power that ranges from 0 dBm to 43 dBm (ImW to 20W), and / or a frequency range from 0.01 GHz to 20 GHz, wherein optionally said frequency range is about 8.4 GHz.

71. The system or device of claim 64, wherein said second surface of said bottom applicator clip comprises a deformable pad.

72. The system or device of claim 71, wherein said deformable pad provides cooling to said appendage when present.

73. The system or device of claim 64, wherein said one or more thermal sensors comprises at least five or at least ten thermal sensors.

74. The system or device of claim 64, which further comprises protective drapes or gel that is configured to surround said subject's appendage when present.

75. The system or device of claim 64, wherein said BTA comprises a surface that is shaped such that it substantially matches the curvature of the top of a nail.

76. The system or device of claim 64, wherein said BTA comprises a size and shape that substantially matches a margin extending beyond the sides of said nail comprising at least one nail fold, that have fungus infected skin.

77. The system or device of claim 64, wherein said subject's appendage is a toenail or a fingernail.

78. The system or device of claim 64, wherein said second dielectric material of said BTA comprises silicone, Teflon, Kapton, FR-4, or polyethylene.

79. The system or device of claim 64, wherein said antenna comprises foil or a thin conductor composed of copper, aluminum, or gold-plated copper.

80. The system or device of claim 64, wherein said antenna is in a single- or multi-resonant slot or double slot, or bowtie or double bowtie configuration on a dielectric substrate, or wherein the antenna comprises a patch antenna.81 . The system or device of claim 64, wherein said shield component comprises: metal foil, metal tape, metal with an insulation barrier, or EMF absorbing fabric, and optionally wherein said metal is selected from copper, brass, nickel, silver, and tin.

82. A method comprising: administering energy from a system or device of any of claims 64- 81 to a subject.

83. The method of claim 82, wherein said subject has a nail and / or nail bed and / or said at least one nail fold, fungal infection.

Images