Therapeutic laser system and method

Abstract

To provide improved methods, systems, and devices for treatment of fungal infection.SOLUTION: A treatment system 300 can include a channel generation system 310 configured to expose with a laser beam focused at a focal volume located in or adjacent to a target tissue. The laser beam can be configured to generate at least a first channel in the infected region. The treatment system can also include a detection system configured to detect a first radiation generated by one or more of (i) the target tissue, (ii) fungi coupled to the infected region in the target tissue, and (iii) an adjacent tissue located proximal to the target tissue as a result of interaction with the laser beam. The treatment system can also include a delivery system 304 configured to deposit an active treatment agent in the at least first channel.SELECTED DRAWING: Figure 3

Description

[Technical field]

[0001] This application is a continuation of U.S. Provisional Patent Application No. 62 / 818,987, filed March 15, 2019. No. 119(e) claims priority under the U.S. Patent Act to No. 6,399,433, filed on Oct. 23, 2006, the entirety of which is expressly incorporated herein by reference. [Background technology]

[0002] Onychomycosis is characterized by discoloration, thickening, and detachment of the nail from the nail bed. It is a fungal infection that can cause nasal congestion. Infected nails tend to look unattractive. This accounts for approximately 50% of nail disorders. Approximately 2-8% of the world's population has nail disorders. Infected with fungal infections. Various microorganisms (e.g. dermatophytes) ), yeast, non-dermatophyte fungi The majority of fungal nail infections are caused by dermatophytes. Dermatophytes are caused by the fungus Mycobacterium tuberculosis, which more commonly infects the toenails than the fingernails. They exist in two forms: the active form, filaments (filamentous cells), and the passive form, spores, which reproduce by hyphae. Both forms can grow deep into the nail plate. Other medical conditions (e.g. Fungal infections may be complicated in people with underlying conditions (e.g., diabetes, peripheral vascular disease, immune disorders). Treatment of onychomycosis is classified based on the location of infection (e.g., toes, fingers, etc.). It is possible.

[0003] Accurate diagnosis of onychomycosis may involve physical and microscopic examination and culture. Histological evaluation using periodic acid-Schiff staining may increase the sensitivity of detecting infection. Treatment of onychomycosis involves determining the causative organism (e.g., dermatophytes, yeast fungi, non-dermatophytes, This can lead to the eradication of the fungus, thereby restoring the infected nail to its normal appearance. Systemic antifungal drugs are a viable treatment but have limited efficacy and can cause hepatitis. It is toxic, causes other serious side effects, and interacts strongly with common statin drugs. Application of topical solutions of antifungal drugs has the following effects: 1) the solutions are effective against hyphal forms of dermatophytes; It is effective against the fungus, but not so effective against the spores, which later produce more hyphae. and 2) the solution has difficulty penetrating the nail plate, making it difficult to treat infected nails. Laser-based therapies are effective in treating onychomycosis. Although we have demonstrated some feasibility to do so, the methods we have employed so far have been of limited effectiveness. This only provides temporary relief and is not curative.

[0004] Additionally, existing methods for treating onychomycosis include topical application of anti-onychomycotic agents to the surface of the nail infected with onychomycosis. However, the effectiveness of such treatment methods is unclear. Efficacy may be limited. For example, topical ointments have limited penetration into the nail plate. In addition, the nail plate is exposed to a wide range of chemicals (e.g., due to the layered structure of the nail plate described above). Topical ointments may not remain on the nail plate long enough to spread (e.g., due to contact between the nail plate and external objects). Topical ointments may be removed by contact with the body (e.g., socks, shoes). Typically, treatment methods may include surgery (e.g., nail removal), and such Surgery can be painful, lead to infection, and require long healing periods. Summary of the Invention

[0005] Thus, improved methods, systems and methods for the treatment of fungal infections (e.g., onychomycosis) are provided. A system and a device are provided.

[0006] The treatment system includes a light axis that moves along the infected area of ​​the target tissue and delivers the light into or to the target tissue. configured to expose the tissue with a laser beam focused at a focal volume located adjacent the tissue. The laser beam may include a channel generating system. The laser beam may have a wavelength in the range of nm. The treatment system can also be configured to generate one channel of: (i) a target (ii) a fungus bound to an infected area within the target tissue; and (iii) a laser beam. by one or more of the adjacent tissues located proximal to the target tissue as a result of interaction with A detection system may be included configured to detect the generated first radiation. The treatment system is also configured to deposit an active therapeutic agent in at least the first channel. The delivery system may include a delivery system that is

[0007] In one implementation, the treatment system includes a detection system that detects the first radiation. and determining the identity of the fungus bound to the infected area in the target tissue. In another implementation, the first radiation may further include a controller configured to: At least one of the fluorophores is from the fungus and is bound to the fungus. In the form of one of the fluorophore, 5-ALA, an ester of ALA, and ppIX. Including the above.

[0008] In one implementation, the channel generating system includes at least a second channel adjacent to the first channel. The at least a second channel is configured to generate a channel for an active therapeutic agent. The received activity in the first channel and the second channel is The sexual therapeutic agent is adapted to diffuse into a portion of the target tissue adjacent to the first channel and the second channel. In another implementation, the target tissue is a nail plate and the adjacent tissue is a nail bed tissue. a first channel extending from an upper proximal surface of the nail plate and a lower distal surface of the nail plate and extending from the lower proximal surface of the nail plate to the The distal surface of the nail bed is adjacent to the nail bed tissue. The detection system detects the relationship between the laser beam and the nail bed tissue. and detecting a second radiation generated due to an interaction between the laser beam and the nail bed tissue. and transmitting a second detection signal indicative of an interaction between the channel generation system. The stem detects an interaction between the laser beam and the nail plate based on receiving the second detection signal. It is configured to terminate.

[0009] In one implementation, the treatment system is adapted to create one or more drill holes in the target tissue. In another implementation, the treatment system may further include a drill system. The present invention relates to a method for treating a vascular endothelial cell, comprising the steps of applying a modulated pressure wave to a target tissue, applying heat to a target tissue, and applying ultrasound to a target tissue. and configured to deliver an active therapeutic agent within the first channel by one or more of the applications. The modulated pressure wave may further include a delivery system for a second laser beam on the target tissue. In one implementation, the delivery system may be configured to direct a beam of light. The first channel is formed by spraying at least an active therapeutic agent into the first channel. The nozzle is configured to deposit an active therapeutic agent within the nozzle.

[0010] In one implementation, the delivery system includes a disposable unit package that includes an active therapeutic agent. a sealant tip configured to be applied to the first channel after deposition of the active therapeutic agent; In another implementation, the active therapeutic agent is a particle, a liposome, a gel, The first channel includes one or more of a polymer, an emulsion, an ointment, and a suspension. The cross-section, which may be oriented perpendicular to the optical axis, may be one of a circle, an ellipse, or a rectangle. In one implementation, the channel generation system can generate a square pattern, a triangular pattern, and a pseudorandom pattern. The pitch of the array of channels is adapted to generate a beam of radiation in response to a given amount of infection of the target tissue. Based on.

[0011] In one implementation, the array of channels is generated by a plurality of laser sub-beams; Multiple laser sub-beams are produced by splitting a laser beam into multiple sub-beams. In another implementation, the distance between the centers of adjacent channels in the array of channels is The spacing is 2-10, 3-7, 4-6, and 4 times the diameter of the channels in the channel array. The channel diameter at the proximal opening of the channel is approximately 30 mm. The spot diameter, which is related to the focal volume, can be in the range of 100 to 200 microns. The diameter of the active therapeutic agent can be about 1 to 25 micrometers. The composition may include one or more of the antifungal agents approved for use in the treatment of cancer.

[0012] The treatment method involves sensitizing the target tissue to form a plurality of separate channels in a predetermined pattern. The dyed region is illuminated with light having a wavelength in the range of about 100 nm to about 400 nm, traveling along an optical axis, and Exposure with a laser beam focused at a focal volume located within or adjacent to the target tissue. Each of the channels may include extending from a top proximal surface of the target tissue to an adjacent set of tissue. each of the channels extending from the upper proximal surface to the lower distal surface of the target tissue proximal to the tissue, and each of the channels extending from the upper proximal surface to the lower distal surface of the target tissue proximal to the tissue, The method includes the step of: Fungi bound to the infected area within the tissue and target tissue as a result of interaction with the laser beam detecting a first radiation generated by one or more of the adjacent tissues located proximate to the The method can further include providing an active substance in at least one of the channels. It may further include depositing a therapeutic agent.

[0013] In one implementation, the target tissue is the nail plate and the adjacent tissue is nail bed tissue. The method further comprises: detecting, by the controller, a first detection signal indicative of the detected first radiation. and determining the identity of the fungus bound to the infected area in the target tissue. In one implementation, the method includes: detecting a second radiation generated due to the interaction of the laser beam with the nail bed; transmitting a second detection signal indicative of an interaction between the tissue and the sensor; and receiving the second detection signal. and terminating the interaction between the laser beam and the nail plate based on the determined result. Cut.

[0014] In one implementation, the method further comprises controlling, by a controller, a reflectance confocal microscope and an optical coherence determining a depth associated with the first channel using at least one of the layer projections; In another implementation, the method further includes applying a modulated pressure wave to the target tissue. applying heat to the target tissue, and applying ultrasound to the target tissue. and delivering an active therapeutic agent in at least one of the channels by one or more of the channels. In one implementation, the method can include sealing the channel after deposition of the active therapeutic agent. The method can further include applying a runt tip. A delivery system including a disposable unit package and a syringe with a sealant tip In one implementation, the method includes applying a laser beam to the target prior to exposure to the laser beam. The active therapeutic agent may further comprise a compound selected from the group consisting of glyceryl phosphate, ... At least one approved antifungal drug.

[0015] Embodiments of the present disclosure will be more fully understood from the following detailed description, taken in conjunction with the accompanying drawings, in which: It will be. [Brief description of the drawings]

[0016] [Figure 1] FIG. 1 is a diagram of an exemplary nail organ suffering from a fungal infection. [Figure 2A] FIG. 2 shows a cross-sectional view of the nail organ of FIG. [Figure 2B] 1 shows the effect of onychomycosis on the nail structure. [Figure 2C] FIG. 1 shows the effect of permeabilizing a diseased nail to provide direct access to the nail bed. [Figure 2D] This shows how deeply dermatophytes can penetrate into the nail plate structure. [Diagram 3] FIG. 1 is a schematic diagram of various subsystems of an exemplary nail treatment system. [Figure 4A] 1 shows an exemplary arrangement of channels in a nail plate. [Figure 4B]1 illustrates an exemplary shape and arrangement of channels in a nail plate. [Figure 5A] 1 shows a scanning electron microscope (SEM) image of an exemplary array of channels in a nail plate. [Figure 5B] A magnified version of the image in FIG. 5A is shown. [Figure 6A] 1 shows a scanning electron microscope (SEM) image of another exemplary array of channels in a nail plate. [Figure 6B] A magnified version of the image in FIG. 6A is shown. [Figure 6C] 1 shows exemplary micrographs of an array of microchannels created in a model nail produced using a pulsed Nd:YAG laser. [Figure 7] 1 shows a micrograph of an exemplary array of channels produced by scanning a DPSS laser beam. [Figure 8] 1 illustrates an exemplary system for improving drug delivery. [Figure 9] 1 includes exemplary images showing the effect of vacuum and pressure on improving drug delivery within laser-drilled channels. [Figure 10] 1 illustrates an exemplary embodiment of a drug delivery system. [Figure 11A] 1 shows an exemplary image of calcein dye penetration. [Figure 11B] 1 shows an exemplary image of calcein dye penetration. [Figure 12A] 11 is a micrograph showing an exemplary effect of vacuum / pressure on the delivery of a dye solution through a microchannel generated using an excimer laser. [Figure 12B] 11 is a micrograph showing an exemplary effect of vacuum / pressure on the delivery of a dye solution through a microchannel generated using an excimer laser. [Figure 13A] 13 is a micrograph showing an exemplary effect of vacuum / pressure on the delivery of a dye solution through a microchannel generated using a DPSS laser. [Figure 13B]13 is a micrograph showing an exemplary effect of vacuum / pressure on the delivery of a dye solution through a microchannel generated using a DPSS laser. [Figure 14] 13B shows images of the cross section of the sample of FIG. 13A at various depths. [Figure 15] 1 illustrates an exemplary embodiment of a treatment system for treating a fungal infection of the nail plate. [Figure 16] 1 shows an exemplary overlap of therapeutic agent effects from various channels. [Figure 17] 1 illustrates an exemplary treatment system. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] Please note that the drawings are not necessarily to scale. It is intended to illustrate only exemplary aspects of the present disclosure and therefore should not be construed as limiting the scope of the present disclosure. Those skilled in the art will appreciate that the present invention is not limited to the above-described embodiment and may be modified without departing from the spirit and scope of the present invention. The systems, devices, and methods described herein are non-limiting exemplary embodiments and are within the scope of the present invention. It will be understood that the scope is defined only by the claims.

[0018] [Definition] Unless otherwise defined, all technical and scientific terms used herein belong to the present invention. In the event of a conflict, This application, including definitions, shall take precedence.

[0019] "Subject" refers to any animal, including mice, rabbits, pigs, sheep, goats, cattle, and primates, including humans. Any animal of the mammalian species, including domestic animals, zoo animals, sport animals or pets. vertebrates, including mammals.

[0020] As used herein, "treat" and "treat The terms "treatment," "treatment," and the like refer to the associated disorder and / or condition. It means to reduce or improve the condition of a disorder or condition, but not to eliminate it. Treating a condition does not seek to completely eliminate the associated disorder, condition, or symptoms. It will be understood that there is no.

[0021] Ranges provided herein are understood to be shorthand for all values ​​within that range. For example, the range 1 to 50 is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 1 2, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 , 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 (in sequence and, unless the context clearly indicates, any number in the group consisting of a number of It is understood to include any combination or subrange.

[0022] In this disclosure, "comprises" and "compris "containing," and "having" "Including" and the like can have the meaning given to them in U.S. patent law, and "including" and the like can have the meaning given to them in U.S. patent law. "consisting essentially of something" (e.g., "consisting of essentia ludes"). "consists essentially of" or "consists essentially of " likewise has the meaning given to it in U.S. Patent Law, where the term is referred to as "open-ended"; The existence of more than what is described changes a basic or novel characteristic of what is described Unless otherwise stated, the presence of more than what is stated is permitted, but prior art embodiments are excluded. .

[0023] Other definitions 4 are apparent in context throughout this disclosure.

[0024] The principles of structure, function, manufacture, and use of the devices, systems, and methods disclosed herein In order to provide a thorough understanding of the principles of the present invention, certain exemplary embodiments are described below. One or more of these embodiments are illustrated in the accompanying drawings. The devices, systems and methods specifically described in and illustrated in the accompanying drawings are intended to be illustrative, but not limiting. The present invention is intended to be illustrative and not restrictive, and the scope of the present invention is defined only by the claims. It will be understood that features illustrated and described in connection with one exemplary embodiment may be applied to other embodiments. Such modifications and variations are within the spirit and scope of the present disclosure. are intended to be within the scope.

[0025] The embodiments of the present disclosure are described in detail with respect to the treatment of onychomycosis. The illustrated embodiments are not limited to, and may be used to treat other medical and / or cosmetic conditions, such as fungal infections. Examples of fungal infections include, but are not limited to, , and onychomycosis.

[0026] Furthermore, in this disclosure, similarly named components of the embodiments generally have similar characteristics. Therefore, in certain embodiments, each feature of each component of a similar name is necessarily Further, the disclosed systems, devices, and methods To the extent that linear or circular dimensions are used in the description of It is not intended to limit the types of shapes that can be used in conjunction with the systems, devices, and methods. Those skilled in the art will appreciate that such linear and circular dimensions are not intended to be construed as limiting the scope of the present invention for any geometric shape. It will be appreciated that dimensional equivalents can be readily determined. The size and shape of those components should be determined at least according to the requirements of the system and device in use. Depending on the anatomy of the subject being examined and the method and procedure in which the system and device are to be used, This can change things.

[0027] FIG. 1 is a diagram of an exemplary nail organ 100 suffering from a fungal infection. , the nail plate 102 formed by the nail matrix (not shown). The nail plate 102 includes a proximal nail fold 112 The nail plate 102 is formed by a thickened layer of skin called the fetal nail 104. The portion of the nail plate 102 adjacent to the PNF (at its proximal end) may be surrounded by The nail plate 10 is formed by the nail matrix and contains a crescent-shaped area called the lunula 106. 2 grows from the proximal end 108 to the distal end 110 of the nail organ.

[0028] As shown in FIG. 1, the nail plate 102 is in a state where it appears to be suffering from a fungal infection (e.g., onychomycosis). The fungal infection can begin in a given area of ​​the nail plate 102 and spread to the nail. It can extend to other areas of the plate 102 (for example, it can extend laterally in the xy plate). along the nail growth direction (along the y direction) If the growth rate of the infected area 114 is slower than the growth rate of the nail, the infected area 114 is The growth rate of the infected area 114 along the nail growth direction is If the growth rate of the nail plate 102 is faster than the rate of infection, the nail plate 102 may remain infected (e.g., (The infection may spread to the lunula.) Fungal infections are caused by the growth rate of the fungus, which depends on the growth of the nail. This can be used to treat, for example, fungal infections. By creating a barrier against the proliferation of This can be achieved by applying topical medications.

[0029] FIG. 2A shows a cross-sectional view of the nail organ 100. The nail plate 102 overlies the nail bed, which contains the capillaries. The nail plate 102 is thin (e.g., about 0.25 to 1 mm), hard, and slightly elastic. It is a semi-transparent convex shape composed of about 80-90 layers of dead, keratinized flattened cells. These layers are composed of numerous intercellular links, membrane coatings, The nail plate 102 is made up of a dorsal layer, a middle layer, and a granule, which are tightly connected to each other via desmosomes. The dorsal layer can be a few cells thick, while the middle layer is thicker. It may be softer and more flexible and may represent the thickest layer of the nail plate 102. The ventral layer is very The nail plate 102 is thin (e.g., only about 1-2 cells thick) and adheres to the underlying nail bed. It can be connected.

[0030] FIG. 2B shows the effect of onychomycosis on the nail apparatus. The nail plate thickens and layers separate. can be done.

[0031] FIG. 2C shows changes in the nail apparatus using a nail treatment system to permeabilize the nail plate. 1 illustrates an exemplary embodiment of a nail bed according to the present invention. The channel shown provides access from the nail plate to the nail bed. but also provides access to the nail plate from the side of the channel.

[0032] FIG. 2D illustrates how deeply dermatophytes can penetrate into the structure of the nail plate 102, as well as The tile-like structure makes it difficult to deliver solution to either the hyphae or the spores. The spores remain dormant until they germinate and re-form hyphae. and can survive for months to years despite the presence of the drug.

[0033] The systems and methods for treating nails described herein may be used to treat fungal infections of the nail plate 102. This allows for the effective and safe treatment of the disease, thereby successfully improving the cosmetic appearance. Such systems and methods may be used for a variety of purposes, including, but not limited to, medical, veterinary, cosmetic, and other medical applications. It will be appreciated that the treatment may be used for a variety of purposes, including cosmetic and aesthetic purposes. 102 (e.g., vertically along the z-axis). (For example, liquid forms, gel forms, gas forms, etc.) Therapeutic agents (in the form of gelatinous fluids) can be added to these channels. A portion of the nail plate 102 that is not readily accessible to a therapeutic agent applied to the surface of 102 (e.g. , the infected area below the surface of the nail plate 102). The channels allow for efficient diffusion of therapeutic agents between the different layers of the nail plate 102. The channels act as repositories of drugs to treat fungal infections along the direction of nail growth. It can function as a barrier that can reduce the rate of proliferation.

[0034] In one implementation, the nail treatment system includes a comprehensive system for the treatment of onychomycosis. The nail treatment system can be used to diagnose fungal infections, treat the nail plate 102 and the area beneath the nail plate 102. Access fungal infections throughout the nail bed, deliver topical antifungal agents, and promote nail growth The nail treatment system can be configured to: Ultraviolet energy (having wavelengths in the ranges of 280-315 nm, 315-400 nm, etc.) (e.g., by creating a channel through the nail plate 102) using a laser to deliver It can provide access to the infected area. After the channel is created, the nail treatment is performed by Antifungal drugs can be deposited within the

[0035] 3 is a schematic diagram of the various subsystems of an exemplary nail treatment system 300. The system may include a diagnostic system 302 and a drug delivery system 304. The diagnostic system 302 includes an infection detection system 306, a profile determination system 308, and The infection detection system may include one or more of the channel generation systems 310. The nature of the infection and / or the area of ​​the nail plate that is infected can be detected. The nature of the infection (e.g. type of fungal infection) is determined by exposing the nail plate to input radiation and the The detected output radiation can be detected by detecting the emitted / reflected output radiation. Based on the power radiation (e.g., the wavelength of the detected output radiation), the type of fungal infection of the nail plate For example, when a given fungus is irradiated with input radiation of a given wavelength, This can lead to the generation of an output fluorescent signal (e.g., fluorescence spectroscopy). The wavelength of the fluorescent signal is then calculated (e.g., by a processor in the controller) to obtain the fluorescence signal of the fungus. The identity of a given fungus can be determined by comparison to a database. Based on this, a course of treatment (e.g., type of therapeutic agent) can be determined.

[0036] The fluorescent signal can also be used to determine areas of the nail plate that are infected. For example, a beam of input radiation having a limited lateral extent (e.g., parallel to the nail plate) can be The part of the nail plate that produces a fluorescent signal is called the fungal infection. Areas that produce no signal but can be designated as affected by fungal infection In some implementations, a camera or sensor (e.g., For example, a charge-coupled device (CCD) or complementary metal-oxide semiconductor (CMOS) image the nail plate. and an image recognition module can identify areas of the nail plate that are affected by fungal infection. It is possible.

[0037] The profile determination system can be used to determine the surface profile of the nail plate. This provides focus information to the channel generation system and provides a basis for pattern generation. The profile can be a structure having a fixed pattern, e.g., an array of lines. Using illuminating illumination, the distortion of the pattern can be used to determine the depth and shape of the surface. Other methods that can be used to determine the surface profile Techniques include interferometry and mechanical scanning using a measurement probe. In an implementation of the method, a grid of lines can be projected onto a surface and characterized. The sensor can see the lines on the surface, and image processing algorithms detect deviations from straightness. If the surface (e.g., the surface of the nail plate) is flat, the pattern can be detected directly. The result is a grid of lines, but the lines appear to be curved when the surface has a contour. Processing algorithms are able to extract a surface profile from the patterns visible on the surface. In some implementations, a focused laser beam can be scanned across a surface. At each point in the scan path, the focus is adjusted (e.g., using an autofocus mechanism). The focus lens can be moved so that the focus is exactly on the surface of the nail. The distance that the focus lens moves in the position is indicative of the surface profile. In one embodiment, interferometry (e.g., optical coherence tomography) is used to determine the surface profile. For example, a plane electromagnetic wave projected onto a nail can interfere with the incident and reflected beams. This allows the detection of phase shifts (e.g., different path lengths) corresponding to the nail contour. In some implementations, confocal microscopy can be used to measure the surface profile of the nail plate. The file can be identified.

[0038] This channel generating system generates channels through the nail plate (e.g., the z-axis as shown in Figure 2C). This can be done, for example, by creating a laser in the nail plate. A laser beam is irradiated onto the nail plate to generate a channel (e.g., by scanning). Scanning can be achieved by directing a laser beam at a part. Use galvanometers to move or modify the beam (e.g., redirect By physically moving the optics used to focus, focus, and collimate the Any number of channels can be used to adjust the channel density. The desired pattern (e.g., linear pattern, circular pattern, hexagon, etc.) can be generated. The density of the channels (e.g., the number of channels per unit area) can be determined by the It can vary in different areas (e.g., along the length of the nail plate). For example, fungal infections Areas of the nail plate where blood flow is more concentrated can be treated to contain more concentrated channels. Cut.

[0039] The individual channels can be made in a variety of geometries. For example, the cross-section of the channel (e.g., a cross section parallel to the surface of the nail plate) may have a rectangular shape, a circular shape, an elliptical shape, etc. Figure 4A shows an exemplary arrangement of channels 402 having an elliptical cross-section. As shown in the figure, the cross section of the channel is aligned along the growth direction of the nail plate 404 (e.g., from the proximal end 40 6 to the distal end 408 along the y-axis) and In some implementations, such cross-sectional geometries For example, fungal infections may be more pronounced in the direction of nail growth compared to the lateral direction. The elliptical cross-sectional geometry shown in FIG. 4A (or , or other geometric shapes extending along a direction transverse to the direction of nail growth) can reduce the spread of fungal infection along the direction of nail growth. The growth rate of the fungal infection (from the proximal end 406 to the distal end 408) is slower than the growth rate of the nail plate. In this case, the growing nail plate can push out the fungal infection.

[0040] The cross-sectional shape / size can vary depending on the depth of the nail plate. The shape and size will be based on the nature of the fungal infection, the amount of therapeutic agent needed to treat the fungal infection, etc. The depth of the channel can be determined by the energy and pulse width of each laser pulse. The number of passes can be determined based on the time the nail plate is exposed to the laser beam. In some implementations, the channel generation system includes a filter that determines the depth of the channel. For example, the nail plate may be fully extended from the nail plate to the nail bed (e.g., in the z-axis). It may be desirable to configure the channels to extend along the nail plate (through the various layers of the nail plate). Such a feedback mechanism allows the laser beam to penetrate the nail bed (e.g., blood vessels in the nail bed). By detecting the fluorescent signal that is generated when the laser beam interacts with the nail In some implementations, the channel generation system The system is designed to detect the fluorescent signal generated by the interaction between the laser beam and the nail bed. When the fluorescent signal is detected, the laser may include a camera or sensor configured to The light source that produces the beam can be turned off, which prevents damage to the nail bed. This can be done.

[0041] In some implementations, multiple laser beams are applied to a mask to produce a multi-layer structure. Multiple sub-beams can be generated simultaneously. Multiple sub-beams can be simultaneously In one implementation, a high power broadband laser operating at 248 nm can be generated. Patterned channel features using a beam excimer laser in conjunction with mask projection The laser can irradiate the mask and then the mask can be A portion of the passing laser beam is sent through a lens to reduce the size of the image on the target. This can be done.

[0042] FIG. 4B shows an exemplary arrangement and shape of channels on the nail plate. As shown in the figure, The shape of the channel can be circular, elliptical (or oblong), rectangular, or spiral. The nails can be arranged in a staggered configuration, a rectangular grid, etc. The nails extend outward toward the distal end. The fungal infection begins at the distal end of the nail and migrates backwards towards the proximal end. Fungi exist in two forms: 1) hyphae, the active form, and 2) spores, the dormant form. The fungus reproduces through spores. The hyphae consume the keratin in the nail plate, causing it to become The drug is effective in treating fungal infections in the form of active hyphae. However, it is not effective in treating spores. Early drug application can treat mycelium, but The remaining spores germinate and form hyphae.

[0043] One exemplary form of treatment, shown in FIG. 4B, is called the "push broom technique." Staggering the channels can provide obstacles to fungal growth. The hyphae move through the nail plate. The staggered channels strengthen the hyphae as shown in the figure. This limits the effective linear fungal migration speed. If the nail's growth rate exceeds the rate at which the fungus can move, the nail will push the fungus away. It may be possible to improve the effectiveness of this technique by loading drugs into the channels. can be improved.

[0044] FIG. 5A shows an exemplary channel array produced by the laser mask setup described above. The scanning electron microscope (SEM) image of the channel is shown. The channels are formed using a 35 micrometer average entrance diameter. and can have a depth of about 300 micrometers. A larger version of the image is shown.

[0045] FIG. 6A is a scan of another exemplary channel array generated by an excimer laser. Scanning electron microscope (SEM) images are shown. The channels were imaged using a 3 × 2 hole array mask. The channels can have an average entrance diameter of about 75 micrometers. FIG. 6B shows an enlarged version of the image in FIG. 6A.

[0046] FIG. 6C shows a photodiode that generates 266 nm pulsed light that is focused through a microlens array. Microchannels generated in model nails using a 300-nm Nd:YAG laser 1 shows an exemplary micrograph of an array of 100 microns of channels. The channels are approximately 50-70 microns in size. The aperture may have an average inlet diameter.

[0047] In one implementation, a diode pumped solid state (DPSS) is used operating at 355 nm. -pumped solid-state lasers are used to generate the channels FIG. 7 shows an example of a DPSS laser beam generated by scanning the beam. A micrograph of an array of channels is shown. The channels have an average inlet diameter of about 70 micrometers. A DPSS laser (e.g., having a numerical aperture (NA) of 0.1) may have a diameter of 1.5 mm. The spot size (using focusing optics) is 4.3 micrometers in diameter. The channel having a diameter of about 70 micrometers has a diameter of 70 micrometers. It can be produced by moving a laser beam within an area.

[0048] In some implementations, the laser beam is an ultraviolet laser (e.g., about 100-2 (having wavelengths in the ranges of 80 nm, 280-315 nm, 315-400 nm, etc.) In some implementations, the laser beam may be an excimer laser (e.g., 15 (operates at 7nm, 193nm, 248nm, 308nm, 351nm, etc.), DPSS Lasers (e.g., operating at 213 nm, 266 nm, 355 nm, etc.), and UV light The laser may be generated by one or more of the other laser systems that generate The width of the laser beam (e.g., the Rayleigh length of a Gaussian beam) is about 100 microns. The amount of oxygen in the atmosphere may be less than one liter.

[0049] Using ultraviolet wavelength laser beams to generate the channels is a step forward compared to longer wavelengths. This has several advantages over the use of long laser beams (e.g. CO2 lasers). For example, a laser beam with a shorter wavelength can produce finer features (e.g., smaller diameters). A therapeutic agent (e.g., deposited within the channel) and This allows for a larger contact area with the nail plate, resulting in finer features. It may be desirable to create a smaller hole, which can be used to create a larger hole. In comparison, it provides a larger effective surface area while maintaining the structural integrity of the nail, and This allows for a higher channel packing density within the nail plate (e.g. 16, which can improve the diffusion of therapeutic agents (e.g., at various depths in the This allows for overlapping ranges of therapeutic agent influence (e.g., from therapeutic agents in adjacent channels).

[0050] The mechanism of channel generation by lasers operating in the UV range is similar to that of longer wavelengths (e.g. The radiation produced by a laser can be different from that produced by a laser having a different wavelength (visible, infrared, etc.). For example, a UV laser The laser can break molecular bonds and prevent / reduce heat generation during channel generation. Lasers operating at larger wavelengths (visible or infrared) channel the light by heating the nail plate. The heat generated can spread in all directions and damage unwanted parts of the nail plate. The size of the waist of a focused laser beam is approximately 100 mm in diameter relative to the laser wavelength. For example, as the wavelength of the laser increases, the waist of the beam increases. This means that lasers operating in the UV range have a much larger beam width than lasers with higher wavelengths. Therefore, by using a UV laser, Better control over channel shape while preventing thermal damage to unwanted areas of the nail plate It is possible.

[0051] In some implementations, one or more needles (e.g., an array of heated needles) are used to A heated needle is inserted into the nail plate at a desired location (e.g., The needle (or the heated needle actuator) is attached to an actuator that can move the needle to the infected area of ​​the In some implementations, the needle can be heated, thereby It is relatively easy to enable the needle to create the channel.

[0052] The nail treatment system includes a drug delivery system for depositing a therapeutic agent (e.g., a topical drug) within the channel. In some implementations, a combination of vacuum and pressure may be used. The therapeutic agent can be delivered in a liquid phase, a gas phase, or a combination thereof. The therapeutic agent can be pumped (e.g., by positive pressure) into the channel. The drug is deposited in the channel by a drug deposition mechanism (e.g., a sprayer or syringe) that can It is possible to do so.

[0053] In some implementations, the properties of the nail plate may be modified prior to / during deposition of a therapeutic agent. For example, chemical enhancers (e.g., keratin enhancers such as papain, urea, and salicylic acid) Dissolving agents, mercaptans ([2-mercaptopropionyl]glycine, zinc, and pyrithio Sodium mercaptomenthone, 8-mercaptomenthone, meso-2,3-dimercaptosuccinic acid), isomers Sodium bisulfite, keratolytic agents (e.g., salicylic acid, urea, guanidine hydrochloride), etc. ) can be applied to the nail plate prior to deposition of the therapeutic agent. Iontophoresis and ultrasound can be applied to the nail plate to enhance the deposition of therapeutic agents within the channels. This can be done.

[0054] When the therapeutic agent is forced into the channel, air is sealed in the channel, causing the nail to escape. This can create a pressure rise because the drug cannot be injected into the hole. may resist complete delivery (e.g., delivery of a therapeutic agent to a particular depth). However, a vacuum may be created to remove air before and / or during delivery. This can enhance drug penetration. Subsequent pressure can further enhance delivery. FIG. 8 illustrates an exemplary system 800 for enhancing drug delivery. As shown in the figure, The drug delivery system is configured to receive a foot 804 having an infected nail plate 806. The nail plate 806 includes a chamber 802 (e.g., a sealed bag or other chamber) that is sealed with the nail plate 806. Treatment of the nail plate (e.g., by using a UV laser beam) After the procedure (i.e., germination, exposure of the nail to UV light, and application of therapeutic agents), the paw can be placed in the chamber. The chamber 802 can be sealed (e.g., by using a vacuum pump). A vacuum can be created within the chamber. This vacuum pressure drives the therapeutic agent into the channel. In some implementations, longitudinal waves (e.g., ultrasonic waves) can be forced into the ) can deliver therapeutic agents into the channels. For example, The Q-switched laser pulse can generate waves (e.g., shock waves) within the nail plate, This allows for the delivery of drugs into the channels. The nail plate 806 can be heated to an elevated temperature to increase the diffusion rate of the therapeutic agent through the nail plate.

[0055] In some implementations, the nail plate can be sealed after deposition of the therapeutic agent. After depositing a therapeutic agent within the channel, the therapeutic agent can be prevented from exiting the channel. A sealant can be applied to the surface of the nail plate, which fills the channels created in the nail plate. The capsule can be a closed reservoir, allowing the therapeutic agent to diffuse into the nail plate over a long period of time. It can be done.

[0056] In some implementations, after a vacuum of about -1 atm, PEG40 is applied at a pressure of about 1 atm. 0, the delivery of the therapeutic agent can be increased. This shows that PEG400 is delivered to the pig skin attached to the cell. Pressure (1 min, +1.0atm), Vacuum (1min, -1.0atm), Pressure (1min, +1.0atm) Active loading was performed by applying a 3 min cycle of 0.05 ml to the sample.

[0057] FIG. 10 illustrates an exemplary embodiment of a drug delivery system 1000. A dispenser package 1002 (e.g., a plastic dispenser attached to a valved syringe) The ampoule (or ampules) can contain a therapeutic agent (e.g., in a liquid phase). 4 is a syringe 1006 configured to deliver a therapeutic agent out of the package 1002. A vacuum is created by retracting the syringe 1006 in the direction 1010. The valve can then be opened to allow the drug to flow into the tip, Then, valve 1012 can be closed. By depressing syringe 1006 In some implementations, the therapeutic agent can be delivered under pressure using a manual pump, an electric The vacuum / pressure can be generated by a powered vacuum / pressure pump or the like. As a rule, other parts of the body, including toes, feet, or nails, should be removed to allow for the application of pressure / vacuum. Parts can be enclosed.

[0058] Treatment should consist of an appropriate antifungal drug approved for the treatment of liquid forms of onychomycosis (e.g., For example, Efinaconazole topical solution (Jublia), Ciclopirox ( enlac), Tavaborole (Kerydin), etc. Therapeutic drugs include one or more of the following trade names (generic drug names): Can be used with: Blis-To-Sol Powder (undecylenic acid), Extin a(Pro)(Ketoconazole), Mycostatin Topical(Pro)( Nystatin), Naftin(Pro)(Naftifine), Nizoral Topi cal(Pro) (ketoconazole), Nyamyc(Pro) (nystatin), Ti nactin (tolnaftate), Zeasorb-AF (miconazole), Zeaso rb-AF Drying Gel (Miconazole), Vusion (Pro) (Miconazole) (Pro) (Ecozonal / Zinc Oxide), Spectazole (Pro) (Ecozonal), Loprox (P ro) (Ciclopirox), Lotrimin AF Athlete's Foot Powder (miconazole), Oxistat (Pro) (oxiconazole), Pe di-Dri(Pro) (nystatin), Penlac(Pro) (ciclopirox) , Xolegel(Pro) (ketoconazole), Ertaczo(Pro) (sertaco Nizoral Shampoo (ketoconazole), Nizoral A -D (ketoconazole), Jublia(Pro) (efinaconazole), Nysto p(Pro) (nystatin), Penlac Nail Lacquer (Cyclopyro) AX), Lamisil AT(Pro)(Terbinafine 6), Kerydin(Pr o) (tavaborole), Pedipirox-4 (ciclopirox), Dermagra n AF (miconazole), Fungi-Nail (undecylenic acid), M-Zole 3 (Miconazole), Absorbine Athlete's Foot (Tolnafta Absorbine Jr Antifungal (tolnaftate), Aft ate (tolnaftate), Aloe Vesta (miconazole), Athletes Foot Cream (terbinafine), Azolen (miconazole), Baza Antifungal (miconazole), Blis-To-Sol (tolnaftate) , Canesten (Clotrimazole 2), Clarus Antifungal (T Lunaftate), CNL8 Nail(Pro)(Ciclopirox), Critic-A id Clear AF (miconazole), Cruex (undecylenic acid), Cruex Prescription Strength (Miconazole), DermaFung al (miconazole), Desenex Antifungal Atheletes Foot Spray Liquid (Miconazole), Desenex Antifu ngal Cream (Clotrimazole), Desenex Antifungal Foot Cream (Miconazole), Desenex Jock Itch (Miconazole) Zol), Ecoza(Pro)(Econazol), Elon Dual Defens e Anti-Fungal Formula (Undecylenic Acid), Exelderm ( Pro)(Sulconazole), Exoderm(Salicylic Acid / Sodium Thiosulfate), F ungi-Guard (Tolnaftate), FungiCURE Pump Spray (Clotrimazole), Fungoid (Miconazole), Ketodan (Pro) ( Ketoconazole), Kuric (ketoconazole), Lamisil AF Defen se(tolnaftate), Lamisil AT Cream(terbinafine), La misil AT Cream for Jock Itch(Pro)(Terbinafy (Pro) (Terbinafine), Loprox TS (Ciclopirox), Lotrimin AF Athlete's Foot Cream (Clotrimazole), Lotrimin AF Deodorant Po Wder Spray (Miconazole), Lotrimin AF Jock Itch Powder Spray (Miconazole), Lotrimin Ultra Ath lete's Foot Cream (Butenafine), Luzu (Pro) (Luricona (butenafine), Mentax(Pro) (miconazole), Micaderm (miconazole) ), Micatin (miconazole), Micro-Guard (miconazole), Mi Ranel AF (Miconazole), Mitrazol (Miconazole), Monist at-Derm(Pro) (miconazole), Mycelex(Pro) (clotrimazole) Mycocide NS (Tolnaftate), Myco Nail A (Undecyl) Silicic acid), Naftin-MP (Naftifine), NuZole (Miconazole), N yata (nystatin), Ony-Clear (miconazole), Pediaderm AF(Pro)(nystatin), Podectin(tolnaftate), Q-Naf tate (Tolnaftate), Rash Relief Antifungal (Mikona Secura Antifungal (miconazole / zinc oxide), Secu ra Antifungal Extra Thick (Miconazole), Soothe &Cool Inzo (Miconazole), Tetterine (Miconazole), Tin actin Jock Itch (Tolnaftate), Tinaderm (Tolnaftate) Tinamar (Tolnaftate), Tinaspore (Tolnaftate), T ing (Tolnaftate), Triple Paste AF (Miconazole), Und elenic (undecylenic acid), Versiclear (salicylic acid / sodium thiosulfate) Hmm).

[0059] The channel can provide persistent access to the infected area, and the The resulting treatment can clear up fungal infections. Fungal infections are caused by spores and hyphae (cytoplasmic In some implementations, the treatment can exist in two forms: The system allows for repeated treatments to address new hyphae emerging from spores. The therapeutic agent delivered into the channels diffuses radially and axially into the nail plate. , creating a sphere of influence around each channel. As channels get closer together, When the effective range is at its maximum, overlapping ranges of influence can occur. In some implementations The spacing between channels can be determined based on the therapeutic agent (e.g., the diffusion characteristics of the therapeutic agent). Cut.

[0060] Figure 11 shows the results from a channel generated using a 2940 nm Er:YAG laser. An exemplary image showing the penetration of calcein dye is shown. The channel is approximately 0.29 mm (290 mm) wide. The images were obtained using a fluorescent confocal microscope, and the intensity was As the images show, the calcein dye is concentrated at the edge of each channel. It penetrates radially from the

[0061] In one implementation, physical diffusion through the model nail material around the channel is an organic solvent. Colors containing Alexa Fluor 405 mixed with dimethyl sulfoxide (DMSO) Alexa Fluor 405 can be used in two-photon excitation. It is a fluorescent probe designed for use in two-photon excitation microscopes. and to visualize in three dimensions (lateral and thickness directions) the diffusion of the pigment solution through the model nail. becomes possible.

[0062] 12A and 12B show microchannels (produced using an excimer laser). Apply a dye solution (e.g., Alexa Fluo mixed with DMSO) to the entire model nail through a filter. 1 is a micrograph showing an exemplary delivery of a dye solution containing r 405. The micrograph in FIG. 12A shows that the For example, channels in a model nail (created using an excimer laser with a single-hole mask) and 790 nm excitation source. The images are filtered to highlight the dye fluorescence. 2A shows that there is little lateral penetration within the nail. Subsequent images also showed almost no fluorescence. This is because the ink barely penetrates into the nail. The micrograph in Figure 12B shows channels in a model nail generated without any optical filters. An image of is shown.

[0063] 13A and 13B show the laser passing through a model nail ("sample") (using a DPSS laser). 14 is an exemplary diagram of vacuum / pressure for delivery of dye solution through a microchannel (generated using This is a micrograph showing the effect of dimethyl sulfoxide (DMSO). A dye solution containing a Fluor 405 can be applied to the surface of the sample, and then The sample is then placed in a vacuum chamber under vacuum (approximately 25 in Hg) (e.g., for approximately 1 minute). The vacuum may be released and more dye may be applied to the sample. The process can be repeated for about 30 minutes.

[0064] The micrograph in FIG. 13A shows a laser beam (e.g., using a DPSS laser with a single-hole mask). The images show the channels and the 790 nm excitation source in a model nail (generated using a 3D filter). The cells were processed to enhance the dye fluorescence. Figure 13A shows substantial fluorescence not only around each hole but also between the holes. This shows that there is increased penetration into the nail compared to Figures 12A and 12B. The micrograph in FIG. 13B shows that the nanoparticles in the model nail were generated without any optical filters. An image of the channel is shown.

[0065] Figure 14 shows images of cross-sections of the sample at various depths. The fluorescence in the images indicates that the dye is thick. The image shows that the dispersion penetrated through the 30 micrometer depth. Shows.

[0066] FIG. 15 is an illustration of a nail treatment system 1500 for treating a fungal infection of a nail plate 1510. 15 shows an embodiment of the nail treatment system. The nail treatment system includes a treatment module 1502 and a controller 150. 4 and a display 1506. The treatment module 1502 may include The treatment module 1502 can be configured to receive a foot having a damaged nail plate. Infection detection system, profile determination system, channel generation system, and drug delivery system The user may use the interface of the display 1506 to via the interface, the desired treatment action (e.g., detection of infection, determination of nail profile, The present invention provides a method for the preparation of a drug-delivery channel using a fluoroscopy technique.

[0067] In one implementation, the interface may prompt a user to connect the subject's foot to the treatment module 150. The controller 1504 can instruct the treatment module to place the foot in position 2. The treatment module detects when the user has used the device (e.g., via a pressure sensor in the treatment module) and notifies the user Icons can be presented to indicate various possible treatment options. 504 receives the user's selection from the display 1506 and notifies the treatment module For example, the controller 1504 can instruct the treatment module 1502 Infection Detection System, Fluorescence Spectroscopy for Fungal Infection, Channel Generation Based on the detected fluorescent image, the controller 1504 may The fungal infection can then be identified and this information can be displayed on the display 1506. In some implementations, the controller 1504 also controls various treatment options (e.g., The user can be provided with a recommended channel characteristic, therapeutic drug, etc. The above treatment options can be selected. Based on the user's selection, the controller 1 504 can instruct the therapy module 1502 to perform the next therapy action. Some implementations of the nail treatment system may provide separate treatment modules for different treatment actions. The system may include a module.

[0068] FIG. 16 shows an exemplary overlap of therapeutic agent effects from various channels 1602-1614. Active therapeutic agents deposited within these channels are then transported outward from the channels (e.g., concentrically). As a result, a portion of the nail plate (e.g., area 162 0) receives therapeutic agent from multiple channels (e.g., channels 1602 and 1608). It is possible to make it possible to do so.

[0069] In one implementation, as shown in FIG. 17, a treatment system 1700 (or treatment system 300 ) configured to expose an infected area of ​​a target tissue with a laser beam traveling along an optical axis. The channel generation system 1702 (or the channel generation system 310) may include For example, as shown in FIG. 17, the channel generating system 1702 may A laser beam 1710 can be directed to an infected area 1712 (e.g., the nail plate) of The laser beam 1710 is directed into or adjacent to the target tissue 1716 (e.g., The focal volume 1714 may be located above the tissue, within the target tissue, on the surface of the target tissue, etc. In some implementations, the laser beam 1710 may have a wavelength of about 100 nm to about 100 nm. The laser beam 1710 may have a wavelength in the range of about 400 nm. One or more channels (eg, a first channel) may be created in 1712 .

[0070] The channel generation system 1702 generates a first channel (e.g., as shown in FIG. 16). One or more adjacent channels can be created. These channels are located at the proximal end 173. 0 to a distal end 1732 next to adjacent tissue 1718 (e.g., nail bed tissue). The first channel and one or more adjacent channels can be adapted to receive an active therapeutic agent. The active therapeutic agent within the channel can diffuse to the portion of the target tissue adjacent to the channel. For example, as shown in FIG. 16, the solution can spread radially from each channel. This allows for the creation of overlapping areas of influence from channels. (e.g., between a first channel and a second channel adjacent to the first channel) In some implementations, the therapeutic range of the active therapeutic agent may be up to The system 1700 includes a drill for creating / drilling channels (or holes) in the target tissue 1716. A drill system (not shown) may be included.

[0071] The treatment system 1700 receives radiation from a detection system 1704 that indicates detected radiation 1720. A controller 1706 configured to receive a first detection signal 1722. The controller 1706 may also generate a signal 1722 (which may further indicate the detected radiation 1720). ) to determine the identity of the fungus bound to the infected area 1712 in the target tissue 1716. In some implementations, the treatment system 1700 may include a The chuck 1710 is then inserted into the target tissue 1716 (e.g., by a drilling system, a laser beam 1710, etc.). The device may include a delivery system 1708 configured to deliver an active therapeutic agent within the device. This can be achieved, for example, by applying modulated pressure waves, applying heat, applying ultrasound, or the like to the target tissue 1716. In some implementations, the modulated pressure wave is applied to the target tissue 17. 16. In some implementations, the controller 1706 may control the reflectance confocal microscope and the optical coherence tomography. At least one of the channels can be used to detect a depth associated with the first channel. .

[0072] The treatment system 1700 comprises a target tissue 1716, an infected area 1712 within the target tissue 1716, and and the fungus bound to the target tissue 171 as a result of interaction with the laser beam 1710. 6. The tissue 1718 is generated by one or more of the adjacent tissues 1718 (e.g., the nail bed) located proximally to the The system may include a detection system 1704 configured to detect radiation 1720 emitted by the The radiation 1720 is fluorescence from the fungus, a fluorophore (e.g., 5- The composition may include one or more of the following: ALA, esters of ALA, and ppIX. In this implementation, the radiation 1720 may be emitted from the proximal surface 1730 (e.g., the first channel may be emitted from the proximal surface 1730). Between the laser beam 1710 and the adjacent tissue 1718 (as it extends to the adjacent tissue 1718) The second radiation may include radiation generated by the interaction of the first and second light beams.

[0073] The detection system 1704 detects the second radiation and detects the laser beam 1710 and the adjacent tissue. A second detection signal (e.g., detection signal 1718) indicative of an interaction between the In some implementations, the IEEE 802.11b protocol can be configured to transmit the IEEE 802.11b protocol (included in US Pat. No. 6,200,317,222). The controller 1706 determines whether the first channel is adjacent tissue 1 based on the second detection signal. Based on this determination, the controller 17 06 may send a control signal 1724 to the channel generation system 1702. Based on No. 1724, the channel generating system 1702 generates a laser beam 1710 and a target The interaction between the target tissue 1716 and / or the adjacent tissue 1718 can be terminated. For example, the channel generating system 1702 may generate a first channel that reaches the adjacent tissue 1718. When this occurs, generation of the laser beam 1710 can be stopped.

[0074] The treatment system 1700 also deposits an active therapeutic agent in at least the first channel. The delivery system may include a delivery system (e.g., the delivery system described in FIG. 10) configured to In some implementations, the delivery system delivers the active therapeutic agent into the first channel. and depositing an active therapeutic agent in the first channel by spraying the active therapeutic agent in the first channel with the The active therapeutic agent may be delivered in the form of particles, liposomes, gels, polymers, emulsions, ointments, suspensions, etc. The active therapeutic agent may include one or more of the following: In some implementations, the delivery system can include a disposable antifungal agent. A syringe (e.g., FIG. 10) may include a unit package and a sealant tip. The disposable unit package may contain an active therapeutic agent. After deposition of the active therapeutic agent, a sealant tip is applied to the first channel. It is possible.

[0075] In some implementations, the cross-section of the first channel may be oriented perpendicular to the optical axis. The cross section can be one or more of a circle, an ellipse, or a rectangle. If the beam 1710 is oriented with its optical axis oriented along the z-axis, the cross section is , can be oriented in the xy plane and can have one of the shapes previously described. In some implementations, the channel generating system 1702 generates a channel in the target tissue 1716. As shown in FIG. 4B, the channel The array may be in one of the following patterns: square, triangular, pseudorandom, etc. The pitch of the channel array can be determined based on the degree of infection of the target tissue 1716. For example, if the target tissue 1716 is highly infected, the pitch In some implementations, the array of channels can be a plurality of lasers. The laser beam can be generated by a single sub-beam, and multiple laser sub-beams can be by splitting a beam (e.g., laser beam 1710) into multiple sub-beams. will be done.

[0076] In some implementations, the distance between the centers of adjacent channels in the array of channels is: The diameter of a channel in an array of channels (e.g., the cross section of the channel perpendicular to the optical axis) The range should be about 2 to 10 times, about 3 to 7 times, about 4 to 6 times, and about 4 to 5 times the diameter of the In some implementations, the diameter of the channel at the proximal opening is about 30 microns. In some implementations, the focal volume can range from 100 to 200 microns. The associated spot diameters can be in the range of about 1 to 25 micrometers.

[0077] Methods for treating various fungal infections (e.g., onychomycosis) for cosmetic or other purposes are described herein. Such methods can be performed by a physician using the systems described herein. However, the user may be a non-physician, such as an esthetician. or other appropriately trained personnel to treat onychomycosis, with or without medical supervision. It will be appreciated that the systems described herein may be used for any purpose.

[0078] One skilled in the art will appreciate further features and advantages of the invention based on the above-described embodiments. Accordingly, the invention is not to be construed as being limited to the specific form shown and described except as expressly permitted by the appended claims. All publications and references cited herein are incorporated by reference. No. 6,399,433, which is incorporated herein in its entirety.

[0079] The subject matter described herein includes the structural means disclosed herein and their structural equivalents. In digital electronic circuits, including computer software, firmware, may be implemented in software or hardware, or a combination of both. The subject matter described herein can be stored in an information carrier (e.g., in a machine-readable storage device). embodied in, or for execution by, or on a data processing device The operation of a device (e.g., a programmable processor, a computer, or multiple computers) One or more programs, such as one or more computer programs, embodied in propagated signals that control the operation of The computer program product may be implemented as a computer program product. Also known as program, software, software application, or code (which is abbreviated as "programming language") means any form of programming language, including compiled or interpreted languages. They can be written in any programming language and can be run as standalone programs or as modules. Such as a component, subroutine, or other unit suitable for use in a computing environment. A computer program may be deployed in any form. A program may be part of another program or a file that holds data. into a single file dedicated to the program in question, or into multiple tailored files (e.g. (e.g., a file that stores one or more modules, subprograms, or portions of code) A computer program can be stored in one computer. It can be deployed in a single site or across multiple sites. Distributed and deployed to run on multiple computers interconnected by a communications network You may do so.

[0080] The process and logic flows described herein, including the method steps of the subject matter described herein, Rows perform the functions of the subject matter described herein by manipulating input data and generating output. One or more programs that execute one or more computer programs to perform functions The method may be implemented by a programmable processor, such as a special purpose logic circuit, e.g. FPGA (Field Programmable Gate Array) or ASIC (Application Specific Integrated Circuit) The process and logic flow may be implemented by the following steps and may be implemented in accordance with the subject matter described herein: The subject device may be implemented as a dedicated logic circuit, such as an FPGA (Field Programmable Gate Array ) or ASIC (Application Specific Integrated Circuit).

[0081] Suitable processors for the execution of a computer program include, by way of example, general purpose microprocessors. Both processors and application specific microprocessors, and digital computers of any kind A processor may be any one or more processors of a computer. Generally, a processor is a read-only and receiving instructions and data from a general purpose memory or a random access memory, or both. The essential elements of a computer are a processor which executes instructions and a memory which stores instructions and data. One or more memory devices for storing data. Generally, a computer stores data in a One or more mass storage devices, such as magnetic disks, magneto-optical disks, or contains an optical disk or is optically connected to transmit and receive data to and from it. An information carrier suitable for carrying computer program instructions and data is, for example, As semiconductor memory devices (e.g., EPROM, EEPROM, flash memory device), magnetic disk (e.g., internal hard disk or removable disk), Includes magneto-optical disks and optical disks (e.g., CD disks and DVD disks) , including all forms of non-volatile memory. The processor and memory may be implemented as special purpose logic circuitry. It may be supplemented by or incorporated into the

[0082] To interact with a user, the subject matter described herein includes a display device for displaying information to a user. Display devices for displaying images, such as CRT (cathode ray tube) monitors or LCD (liquid crystal displays) a display monitor, and a keyboard and display that allow the user to provide input to the computer A computer with a pointing device (e.g., a mouse or trackball) Other types of devices can be used to interact with the user. For example, the feedback provided to the user can be any form of sensory feedback. feedback (e.g. visual feedback, auditory feedback, haptic feedback) The input from the user can be in any form, including acoustic input, speech input, or tactile input. You can receive it at.

[0083] The techniques described herein may be implemented using one or more modules. As used herein, the term "module" refers to computing software, Computing firmware, computing hardware, and / or However, in the narrowest sense, a module is a combination of hardware, Software not implemented in firmware or readable by a non-transitory processor The Software is not to be construed as software stored on a removable recordable storage medium (i.e. (i.e., modules are not software.) In fact, a "module" is a processor At least some physical non-transient hardware, such as a Two different modules may use the same physical hardware. can be shared (e.g., two different modules can share the same processor and network The modules described herein may be implemented in a variety of ways. Combine, integrate, separate, and / or replicate to support various applications. Also, the functions described herein as being implemented in specific modules may be implemented in various ways. The functions performed in a particular module may be implemented instead of, or in addition to, the functions performed in a particular module. The present invention may be implemented in one or more other modules and / or in one or more other devices. Additionally, the modules may be connected to multiple devices and / or other devices that may be local or remote to each other. Modules can be implemented across multiple components, and can be deployed from one device to another. Can be moved and added to another device and / or both devices It can also contain modules.

[0084] The subject matter described herein includes back-end components (e.g., data servers), middle-tier components (e.g., data servers), a software component (e.g., an application server), or a front-end component (e.g., For example, a graphical user interface that allows a user to interact with an implementation of the subject matter described herein. a client computer having a digital user interface or web browser; ), or such back-end components, middleware components, and front-end The present invention may be implemented in a computing system including any combination of the following components: The components of the system may communicate digital data in any form or medium, e.g. They can be interconnected by a communication network. Examples of communication networks include Local Area Networks ("LANs") and Wide Area Networks ("WANs") ), for example the Internet.

[0085] The terminology used in this application throughout the specification and claims is intended to be construed as being in accordance with the basic principles to which it pertains. Modify any quantitative expression that can vary within acceptable limits without causing significant changes in function. Accordingly, the terms "about" and "substantially" are applicable to Values ​​qualified by "stan- tally" are limited to the precise value specified. In at least some cases, the approximation statement refers to the nature of the equipment used to measure the value. Combinations of range limitations may be used throughout the specification and claims. and / or may be interchangeable, and such scope shall be specified unless the context or language specifically requires otherwise. Unless otherwise specified, all subranges contained therein are included.

Claims

1. 1. A treatment system comprising: a channel generating system including a laser configured to expose an infected region of a target tissue with a laser beam traveling along an optical axis and focused at a focal volume located within or adjacent to the target tissue, the laser beam having a wavelength in a range of about 100 nm to about 400 nm, the channel generating system configured to generate at least a first channel within the infected region; a detection system including a sensor configured to detect a first radiation generated by one or more of: (i) the target tissue, (ii) fungus bound to the infected area within the target tissue, and (iii) adjacent tissue located proximal to the target tissue as a result of interaction with the laser beam; and a delivery system including a reservoir configured to hold an active therapeutic agent and to deposit the active therapeutic agent within the at least first channel; Equipped with the channel generation system is configured to generate an array of channels in the target tissue, the pitch of the array of channels being based on the degree of infection of the target tissue; Treatment system.

2. The treatment system of claim 1 , further comprising a controller configured to receive a first detection signal from the detection system indicative of the detected first radiation.

3. 3. The treatment system of claim 2, wherein the first radiation is at least one of fluorescence from the fungus and a fluorophore bound to the fungus, and the controller is configured to determine an identity of the fungus based on the first detection signal.

4. The therapeutic system of claim 3 , wherein the fluorophore comprises one or more of 5-ALA, an ester of ALA, and ppIX.

5. 3. The treatment system of claim 2, wherein the channel generation system is configured to generate at least a second channel adjacent to the first channel, the at least second channel configured to receive the active therapeutic agent, and the received active therapeutic agent in the first and second channels configured to diffuse to a portion of the target tissue adjacent to the first and second channels.

6. 3. The treatment system of claim 2, wherein the target tissue is a nail plate and the adjacent tissue is nail bed tissue, the first channel extends from an upper proximal surface of the nail plate and a lower distal surface of the nail plate, the lower distal surface of the nail plate being adjacent to the nail bed tissue.

7. the detection system is configured to detect second radiation generated due to an interaction between the laser beam and the nail bed tissue and transmit a second detection signal indicative of the interaction between the laser beam and the nail bed tissue; The treatment system of claim 6 , wherein the channel generating system is configured to terminate an interaction between the laser beam and the nail plate upon receipt of the second detection signal.

8. The treatment system of claim 1 , further comprising a drill system configured to generate one or more drill holes in the target tissue.

9. 10. The treatment system of claim 1, further comprising a delivery system configured to deliver the active therapeutic agent within the first channel by one or more of application of a modulated pressure wave to the target tissue, application of heat to the target tissue, and application of ultrasound to the target tissue.

10. 10. The treatment system of claim 9, wherein the modulated pressure wave is generated by directing a second laser beam on the target tissue.

11. The treatment system of claim 1 , wherein the delivery system is configured to deposit the active therapeutic agent in the first channel by spraying at least the active therapeutic agent into the first channel.

12. 10. The treatment system of claim 1, wherein the delivery system includes a disposable unit package comprising the active therapeutic agent and a syringe comprising a sealant tip configured to be applied to the first channel after the deposition of the active therapeutic agent.

13. The therapeutic system of claim 1 , wherein the active therapeutic agent comprises one or more of a particle, a liposome, a gel, a polymer, an emulsion, an ointment, and a suspension.

14. The treatment system of claim 1 , wherein a cross-section of the first channel oriented perpendicular to the optical axis can be one of a circle, an ellipse, or a rectangle.

15. 10. The treatment system of claim 1, wherein the array of channels in the target tissue is based on one or more of a rectangular pattern, a triangular pattern, a circular pattern, an oval pattern, a spiral pattern, and a pseudo-random pattern.

16. 16. The treatment system of claim 15, wherein the array of channels is generated by a plurality of laser sub-beams, the plurality of laser sub-beams being generated by splitting the laser beam into a plurality of sub-beams.

17. The distance between the centers of adjacent channels in an array of channels is 16. The treatment system of claim 15, wherein the diameter is one of 2 to 10 times, 3 to 7 times, 4 to 6 times, and 4 to 5 times the diameter of the channel.

18. The treatment system of claim 15, wherein the diameter of the channel at the proximal opening is in the range of about 30 microns to 200 microns.

19. 10. The treatment system of claim 1, wherein the spot diameter associated with the focal volume is about 1-25 micrometers.

20. The treatment system of claim 1 , wherein the active therapeutic agent comprises one or more of the antifungal agents approved for the treatment of onychomycosis.

21. 1. A method of operating a therapeutic system including a channel generation system, a detection system, and a delivery system, comprising: a laser of the channel generating system exposing an infected area of ​​a target tissue to a laser beam having a wavelength in a range of about 100 nm to about 400 nm, traveling along an optical axis and focused at a focal volume located within or adjacent to the target tissue to form an array of channels in the target tissue, the array of channels having a pitch based on the degree of infection of the target tissue; a sensor of the detection system detecting a first radiation generated by one or more of the target tissue, fungus bound to the infected area within the target tissue, and adjacent tissue located proximate to the target tissue as a result of interaction with the laser beam; holding an active therapeutic agent in a reservoir of the delivery system, the delivery system depositing the active therapeutic agent in at least a first channel of the array of channels; A method comprising:

22. 22. The method of claim 21, wherein the target tissue is the nail plate and the adjacent tissue is nail bed tissue.

23. a controller receiving a first detection signal from the detection system indicative of the detected first radiation; a controller determining an identity of the fungus bound to the infected area in the target tissue based on the first detection signal; 23. The method of claim 22, further comprising:

24. the detection system detecting a second radiation generated due to an interaction between the laser beam and the nail bed tissue; the detection system transmitting a second detection signal indicative of an interaction between the laser beam and the nail bed tissue; the channel generating system terminating the interaction between the laser beam and the nail plate based on receipt of the second detection signal; 24. The method of claim 23, further comprising:

25. 24. The method of claim 23, further comprising the controller determining a depth associated with the first channel using at least one of reflectance confocal microscopy and optical coherence tomography.

26. The treatment system further includes a delivery system, the method further comprising: the delivery system applying modulated pressure waves to the target tissue, applying heat to the target tissue, and 22. The method of claim 21, further comprising delivering the active therapeutic agent in the first channel by one or more of applying ultrasound to a target tissue.

27. 22. The method of claim 21, wherein the delivery system includes a syringe comprising a disposable unit package comprising the active therapeutic agent and a sealant tip, the method applying the sealant tip to the first channel after depositing the active therapeutic agent.

28. 22. The method of claim 21, further comprising softening the target tissue prior to exposure to the laser beam.

29. 22. The method of claim 21, wherein the active therapeutic agent is at least one antifungal agent to treat onychomycosis.

30. 22. The method of claim 21, wherein each channel of the array of channels extends from an upper proximal surface of the target tissue to a lower distal surface of the target tissue proximal to an adjacent tissue.

31. 31. The method of claim 30, wherein each channel of the array of channels has an opening in the top proximal surface having a diameter in the range of about 30 to 200 microns.

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