US20130338626A1 - Photopatterning of skin - Google Patents

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Definitions

• the present application relates, in general, to the field of treating skin for aesthetic and/or health and/or other purposes.
• this application relates to methods and systems for controlling the delivery of materials into or onto skin.
• a desired pattern may be formed by delivering a photoresponsive material to the skin and exposing the skin to light or other electromagnetic energy to cause a reaction or conversion of the photoresponsive material.
• a photoresponsive material may be delivered into or onto the skin in a pattern.
• patterned light may be delivered to the skin.
• One or both the photoresponsive material and light may be patterned in order to form a desired distribution of material.
• Materials distributed in or on the skin may have a variety of properties for aesthetic, cosmetic, functional, health, or medical purposes.
• FIG. 1 illustrates focusing of light in a skin region to produce modification of a photoresponsive material
• FIG. 2A illustrates transformation of a photoresponsive substance from a first form to a second form with exposure to light
• FIG. 2B illustrates cross-linking of a photoresponsive substance on exposure to light
• FIGS. 3A-3C illustrate photopatterning of skin by targeted application of light
• FIG. 4A illustrates topical application of a photoresponsive material
• FIG. 4B illustrates diffusion of topically applied photoresponsive material into the skin
• FIG. 5A illustrates hypodermal injection of photoresponsive material
• FIG. 5B illustrates diffusion of injected photoresponsive material
• FIG. 6 illustrates injection of photoresponsive material into skin with a microneedle array
• FIG. 7 depicts diffusion of photoresponsive material into skin from a capillary
• FIG. 8 depicts a skin region including a photoresponsive substance
• FIG. 9 depicts targeted application of light to a skin region including a photoresponsive substance
• FIG. 10 depicts an embodiment of a system for controlled delivery of light to skin
• FIG. 11 is a flow diagram of a method of forming a pattern in a skin volume
• FIG. 12 is a flow diagram of a further method of forming a pattern in skin
• FIG. 13 is a flow diagram of a further method of forming a pattern in skin
• FIG. 14 is a block diagram of a system for targeted application of light to skin
• FIG. 15 is a block diagram of a system for targeted application of light to skin
• FIG. 16 is a block diagram of an embodiment of a system for controlled delivery of light to skin
• FIG. 17 is a flow diagram of a method producing a pattern on a surface
• FIGS. 18A-18D depict steps of a method of patterning skin
• FIG. 19A illustrates an embodiment of a mask with a decorative pattern
• FIG. 19B depicts use of the mask depicted in FIG. 19A ;
• FIG. 19C illustrates a decorative pattern formed on a skin surface with the use of the mask depicted in FIG. 19A ;
• FIG. 20 is a flow diagram of a method of forming a patterned distribution of material in skin
• FIG. 21A illustrates delivery of patterned light to a treated skin surface
• FIG. 21B illustrates a pattern formed on a skin surface by the patterned light depicted in FIG. 21A ;
• FIG. 22 is a flow diagram illustrating variations of methods for photopatterning of skin
• FIGS. 23A-23C illustrate steps of forming a patterned distribution of material in skin
• FIG. 24 is a flow diagram illustrating variations of methods for photopatterning of skin
• FIGS. 25A-25C illustrate patterning of skin by patterned delivery of photoresponsive material combined with patterned delivery of light
• FIG. 26 is a block diagram of a system for photopatterning of skin
• FIG. 27 is a flow diagram of a method of photopatterning skin including reversing the photoreaction
• FIG. 28 is a flow diagram of a method of photopatterning skin including removing the modified form of the photoresponsive material
• FIG. 29 is a flow diagram of a method of photopatterning skin including removing unmodified photoresponsive material from the skin;
• FIG. 30 is a flow diagram of a method of photopatterning an active chemical compound in the skin
• FIG. 31 is a flow diagram of a method of manufacturing a device for delivering patterned light
• FIG. 32 is a flow diagram of a further method of manufacturing a device for delivering patterned light.
• FIG. 33 is a block diagram of a system for delivery of patterned light.
• Patterned distributions of materials in skin may have various applications, including but not limited to aesthetic, cosmetic, functions, medical or health purposes. Patterned distributions of dyes, pigments, or other light absorbing, reflecting, or emitting materials, (or any other materials that may produce a visually or optically detectable effect) may be used for aesthetic, decorative, or cosmetic purposes (for example, as tattoos or permanent or semi-permanent cosmetics).
• Detectable markings which may be detectable visually or optically, or by electrical, magnetic, acoustic, or various other detection methods, may have functional applications, as well, for example, marking the location of a surgical site on a patient, or for providing permanent or semi-permanent identifying markings, e.g., on pets, livestock, etc.
• Patterned distributions of materials having pharmaceutical activity may be used to selectively treat various structures in or near the skin surface.
• Treatment targets may include skin lesions, including cancerous and precancerous skin lesions, moles, warts, and pimples. Treatment may also be applied to disorders of various skin structures, for example, capillaries, veins, sweat glands, and hair follicles.
• patterned distributions of structural materials may be used for cosmetic or reconstructive surgery applications.
• structural materials e.g., materials that add strength, form, shape, bulk, resilience, or other desired structural or mechanical properties to skin, connective tissue, cartilage, and so forth
• the patterned material is a biologically active compound intended to treat a specific medical problem, only transient presence of the patterned material may be desired.
• FIG. 1 illustrates modification of a photoresponsive material in skin caused by delivery of light.
• molecules or particles of photoresponsive material 10 are distributed throughout skin region 12 , and light 14 is targeted to a specific location by lens 16 , where it produces a reaction or other modification of one or more molecules or particles of photoresponsive material 10 to produce modified form 11 .
• Skin region 12 includes stratum corneum 18 and keratinocyte layer 20 , which together form epidermis 22 , and dermis 24 . Also shown is hair follicle 26 and hair 28 .
• Photoresponsive material 10 may be distributed in the form of molecules, clusters or aggregations of molecules, particles, gels, solutions, emulsions, suspensions, sprays, fluids, powders, among others.
• photoresponsive material refers to a material (compound, element, composite material, etc.) that undergoes or participates in a reaction, interaction, transformation, modification, phase change, change in energetic state, etc.) to produce a reaction product, or modified form, indicated by reference number 11 in FIG. 1 , having one or more different activities or properties than the original or ‘unmodified’ photoresponsive material.
• a “modification”, as used herein may include chemical reactions, changes in energetic state, phase, conformation, associations, aggregations, formation of bonds or other interactions (e.g.
• Photoresponsive material may be any material that is responsive or sensitive to light to change from a first state to a second state, by itself or in cooperation or reaction with other materials present.
• a photoresponsive material may undergo a modification that results in a modification to a secondary material, in which it is the secondary material that produces an effect in the skin.
• the photoreactive material may be employed as a light-specified ‘mask’ which then is used to control the exposure of skin not so ‘masked’ to subsequent processing.
• Photoresponsive material may include mixtures of materials that react or interact upon exposure to light.
• FIG. 2A depicts a change in conformation produced by exposure to light, in which photoresponsive material 10 is converted from a first state 10 to a second state 11 .
• FIG. 2B depicts cross linking of multiple molecules 30 of photoresponsive material produced by exposure to light, to form crosslinked network 31 .
• Conversion of a photoreactive material from an unreacted to a reacted form may include conversion from inactive to active form, from active to inactive form, from colored form to non-colored form, from a darker form to a lighter oner (or vice versa), from a more-scattering form to a less-scattering one (or vice versa), from a first color to a second color, or any combination of these.
• Conversion of a photoreactive material from an unreacted form to a reacted form may include a changes in the scattering or absorption properties of the photoreactive material for light of a given waveband.
• Various methods of delivering photoresponsive material and light to a skin region may be used to produce a patterned distribution of a material in the skin region.
• One or the other or both of the photoresponsive material and the light may be delivered in a targeted fashion in order to produce a patterned distribution of material in the skin.
• a patterned distribution of a material in or on skin may be produced by delivering a photoresponsive material to at least a skin region of a subject in a relatively non-targeted fashion, and delivering targeted light to the skin region according to a pattern.
• the targeted light may have a wavelength content, time-averaged flux and/or fluence sufficient to cause a transformation of the photoresponsive material to a modified form.
• the method may include delivering targeted light to the skin region according to a pattern by delivering targeted light to a plurality of locations in the skin region according to a pattern.
• a patterned distribution of the modified form of the photoresponsive material may then be formed. This general approach is illustrated in FIG. 3A-3C . In FIG.
• FIG. 3A a skin region 100 is illustrated. Photoresponsive material has been applied to a portion 102 of skin region 100 . Focused light 106 from light source 108 is delivered to location 110 a , which is one of multiple locations 110 a - 110 j within portion 102 .
• FIG. 3B illustrates delivery of light 106 to location 110 a , where photoresponsive material is converted to a modified form, indicated by a dark circle.
• FIG. 3B depicts multiple locations 110 b - 110 j that have previously been exposed to light to cause modification of photoresponsive material.
• Light source 108 may be positioned with respect to skin region 108 by a linkage 112 .
• FIG. 3C depicts a pattern of modified material at locations 110 a - 110 o.
• Photoresponsive material in relatively non-targeted fashion may be accomplished by various methods, which may depend on various factors, including the type of photoresponsive material to be used, desired depth of delivery of the material in the skin, the size of the area in which a patterned distribution of material is to be produced.
• photoresponsive material may be delivered to the skin topically.
• a carrier material 130 containing a photoresponsive material 132 may be placed on a skin surface 134 .
• Photoresponsive material 132 may diffuse out of carrier material 130 and into skin 12 , as shown in FIG. 4B .
• Skin 12 includes epidermis 22 and dermis 24 .
• Diffusion of photoresponsive material 132 may be enhanced by electrophoresis or by the presence of solvent or ‘carrier’ chemicals such as DMSO or EDTA in certain embodiments (see, e.g., “Photodynamic Therapy”, Medscape Dermatology 3(2), 2002, incorporated herein by reference.
• Photoresponsive material may be delivered to at least a skin region of a subject topically in various forms, including, for example, an aerosol, cream, emulsion, gel, liquid, vapor, gas, lotion, patch, or powder or combinations of these.
• a general distribution of a photoresponsive material within a skin region may be obtained by injecting the photoresponsive material 132 into skin 12 with an hypodermic needle 140 , as depicted in FIG. 5A .
• Photoresponsive material 132 may be in a liquid carrier solution 136 , or in a suspension, an emulsion, or any other form suitable for delivery via a hypodermic needle. This approach may be suitable if the diffusion or dispersion of the photoresponsive material away from the injection site produces an acceptable (e.g., sufficiently uniform) distribution of photoresponsive material, as depicted in FIG. 5B , within an acceptable amount of time.
• photoresponsive material may be distributed into a skin region 12 with the use of a microneedle array 150 , as depicted in FIG. 6 .
• Photoresponsive material 132 may be injected below stratum corneum 18 of skin region 12 with the use of a microneedle array 150 .
• photoresponsive material to be delivered via microneedle array 150 may be carried in a carrier fluid 152 that is adapted for use with a microneedle array.
• photoresponsive material 132 that can be obtained within skin region 12 may depend on the combination of injection methodology and photoresponsive material used. For example, smaller molecules may diffuse or disperse more readily from the injection site than may larger molecules. In addition, the presence of certain functional groups may cause some photoresponsive materials to be taken up by certain tissues or cell types. Accordingly, photoresponsive materials may be selected or designed for use in combination with certain delivery mechanism and for preferential delivery to, retention by, or processing by certain tissues or cells.
• photoresponsive materials to have certain diffusion or selective uptake-or-retention-or-processing properties may be performed by a person of skill in the relevant art, for example, as described in Pogue and Hasan, “Targeting in Photodynamic Therapy and Photo-Imaging, Optics & Photonics News, August 2003, pp. 36-43, which is incorporated herein by reference.
• a photoresponsive material may be delivered to at least a skin region of a subject by delivering the photoresponsive material to the subject systemically.
• photoresponsive material may be delivered to the subject orally in an ingestible formulation, via an inhalant, via intravenous or other ‘deep’ injection modalities or via various other systemic routes.
• a photoresponsive material may be delivered via injection, but subsequently carried throughout the body by the blood stream.
• a systemically delivered photoresponsive material 132 may be carried in the blood stream (e.g., in capillary 160 ) and diffuse out into the skin region of interest, which in this example is skin region 12 .
• the photoresponsive material may distribute uniformly throughout the subject's body, or may distribute preferentially to certain regions, tissues, or cells of the body.
• the photoresponsive material may be attached to a carrier molecule compounded in various ways as known to those of skill in the arts of drug delivery, in order to produce a desired distribution of photoresponsive material within the subject's body.
• FIG. 8 depicts the arm 200 of a subject, showing a skin region 202 in which a photoresponsive material is distributed.
• photoresponsive material may be distributed only to the skin region of interest (skin region 202 in the present example), by, for example, topical application or local injection, or it may be distributed to a larger portion of the subject's body (up to and including the entire body), of which the region of interest is a part.
• patterned light 204 is delivered to skin region 202 from light source 206 to cause modification of the photoresponsive material to produce a patterned distribution 208 of the modified material in skin region 202 .
• FIG. 10 provides a general illustration of a device 300 that may be used to produce a patterned distribution of light.
• Controller 301 controls the deliver of light 302 from light source 304 via optical system 306 .
• Device 300 may be positioned by a mechanical linkage 112 supported by a base 140 .
• Light 302 may be delivered at different x, y positions on the skin surface (e.g. x 1 , y 1 , x 2 , y 2 , x 3 , and y 3 in FIG. 10 ), as well as at different depths or z positions (e.g. z 1 , z 2 , and z 3 in FIG. 10 ) below the skin surface 134 .
• Each location may be characterized by an x coordinate and y coordinate in an effectively planar portion of the skin region. Similarly, each location may be characterized by z coordinate corresponding to the depth of the location below a surface of the skin region. In some applications, the z coordinate may be selected for each location such that a pattern is formed in the epidermis of the skin region. In other applications, the z coordinate may be selected for each location such that a pattern is formed in the dermis of the skin region, or even below the dermis.
• a method as depicted in FIG. 11 may be used for forming a pattern in a skin volume.
• a photoresponsive material is delivered to at least a skin volume of a subject, the skin volume including a region having a depth underlying a skin surface having an area.
• light of a wavelength band, time-averaged flux and/or fluence sufficient to cause modification of the photoresponsive material may be aimed and focused at a plurality of locations within the volume, with at least a portion of the plurality of locations being at different depths within the region.
• FIG. 12 depicts steps of a method of forming a patterned distribution of material in skin, including delivering a photoresponsive material to at least a skin region of a subject at step 452 and delivering targeted light to the skin region according to a pattern, the targeted light having a wavelength content, time-averaged flux and/or fluence sufficient to cause a transformation of the photoresponsive material to a modified form, at step 454 .
• FIG. 12 depicts steps of a method of forming a patterned distribution of material in skin, including delivering a photoresponsive material to at least a skin region of a subject at step 452 and delivering targeted light to the skin region according to a pattern, the targeted light having a wavelength content, time-averaged flux and/or fluence sufficient to cause a transformation of the photoresponsive material to a modified form, at step 454 .
• FIG. 13 depicts a related method, which includes delivering a photoresponsive material to at least a skin region of a subject at step 472 and delivering targeted light to a plurality of locations in the skin region according to a pattern, the targeted light having a wavelength content, time-averaged flux and/or fluence sufficient to cause a transformation of the photoresponsive material to a modified form, in step 474 .
• FIG. 14 is a block diagram of a system 500 for delivering patterned light.
• System 500 includes a light source 502 capable of producing light 503 of at least one defined wavelength band, and a controllable optical system 504 .
• Controllable optical system 504 is configured to receive control signal 506 generated according to a pattern 508 , and responsive to the control signal 506 to aim and focus light 503 from the light source 502 onto one or more selected skin locations of the plurality of skin locations 510 a - 510 p according to pattern 508 .
• Pattern 508 may represent a desired distribution of a material to a plurality of locations in or on skin region 510 .
• System 500 may also include electronic circuitry 512 configured to limit the fluence of light 503 produced by the light source 502 to levels that are non-damaging or not significantly damaging to skin.
• Controller 514 which may be, for example, a microprocessor, may perform computations used to produce control signal 506 for controlling controllable optical system 504 , and light source drive signal 515 for driving light production by light source 502 .
• Electronic circuitry 512 may function to limit light source drive signal 515 to limit light generation to safe levels.
• a system for delivering patterned light to skin may include a light source capable of producing light of at least one defined wavelength band, a controllable optical system, and electronic circuitry configured to limit the fluence of light produced by the light source to levels that are non-damaging or not significantly damaging to skin.
• the controllable optical system may be configured to receive a control signal generated according to a pattern representing a desired distribution of a material to a plurality of locations in or on a skin region, and responsive to the control signal to aim and focus light from the light source onto one or more selected skin locations of the plurality of skin locations according to the pattern.
• the system for delivering patterned light may also include an imaging device adapted for imaging a skin region containing at least a portion of the plurality of skin locations.
• the system may include a device driver including one or more of hardware, software, or firmware for generating the control signal based upon pattern data stored in a machine readable medium.
• the controllable optical system may include one or more deflectors configured to aim light from the light source, and the position of at least one of the one or more reflectors may be controllable to aim light toward at least one of the plurality of skin locations.
• the controllable optical system may include a positioner adapted to adjust the position of the light source.
• Deflectors may include mirror-type reflectors and surface-acoustic wave (SAW) Bragg-type deflectors, as well as electrically-steered refractive elements.
• SAW surface-acoustic wave
• Patterned light may be delivered in the form of discrete pulses applied at multiple locations, as depicted in FIG. 14 . Patterned light may also be delivered by sweeping a focused beam of light across a skin surface in a continuous pattern, for example, as depicted in FIG. 15 . A beam may be moved across the skin surface with the use of a scanning mirror or functionally-equivalent optical systems of other types, the design and use of which is well known to those of skill in the art. Patterned light may also be delivered in some combination of continuous and discrete light; for example, a beam may be swept across the skin surface to form contiguous portions of a pattern, but turn on and off as the beam is moved to non-contiguous portions of the pattern.
• FIG. 15 depicts a system 600 including a controllable positioning system 602 that may be used to move a beam of light 604 over a skin surface 606 and to adjust the positioning of light from the light source on a skin region.
• System 600 may include a controllable optical system 608 that includes one or more deflectors 610 configured to aim light 604 , from the light source 612 .
• the position of at least one deflector 610 may be controllable to aim light 604 toward at least one of the plurality of skin locations.
• Controllable optical system 608 may include a positioner adapted to adjust the position of light source 612 .
• Light source 612 may be capable of producing light 604 of at least one defined wavelength band.
• System 600 may also include memory 614 capable of storing a pattern 616 in machine-readable form representing a plurality of locations within a skin region to which light 604 from light source 612 is to be directed.
• system 600 may include one or more optical components capable of focusing light 604 from the light source 612 at a specific depth within a skin region 12 in response to a control signal 618 , controller 620 configured to generate control signal 618 for driving controllable positioning system 602 to direct light onto a plurality of skin locations according to pattern 616 stored in memory 614 .
• Controller 620 may be configured to generate a control signal from driving one or more optical components to adjust the focusing of light 604 at different depths and at different skin locations according to pattern 616 .
• Deflectors 610 may be controllable deflectors configured to aim light 604 from light source 612 , wherein the position of at least one of the one or more deflectors 610 is controllable to aim light toward any of the plurality of skin locations.
• Controller 620 may include one or more of hardware, software, and firmware.
• controller 620 may include a microprocessor.
• system 600 may include an imaging device, which may be for example, a CCD camera.
• FIG. 16 is a block diagram of different aspects of a system 700 for delivering patterned light to a skin region 12 .
• System 700 may include light source 702 and optical system 704 , which directs and focuses light 706 from light source 702 .
• Overall system operation may be controlled by processor 708 , which may be, for example, a microprocessor, powered by power supply 710 .
• Processor 708 may execute commands from executable code 712 to generate signals 714 and 716 , which are sent to light source driver 718 and optical driver 720 , respectively.
• Light source driver 718 which may include hardware, software, firmware, or a combination thereof, drives operation of light source 702 .
• Optical driver 720 which also may include hardware, software, firmware, or a combination thereof, drives operation of optical system 704 , via position control module 722 and focus control module 724 .
• System 700 may be used to deliver targeted light to a plurality of locations under software control and/or under microprocessor control.
• FIG. 17 outlines a method that includes delivering patterned light of a restricted wavelength band to a skin surface coated with a photosensitive material, wherein the patterned light is capable of interacting with the photosensitive material to produce a visible pattern on the coated surface, as shown at step 752 of the flow diagram.
• the photosensitive material may be applied to the surface.
• Light may be delivered to different locations in sequence, in either discrete or continuous fashion. Patterned light as used in certain embodiments may be produced with the use of a controllable optical system that is controllable to focus the light source on at least two of a plurality of skin locations in sequence. In some embodiments, a controllable optical system may be used that is controllable to focus the light source on at least two of a plurality of skin locations simultaneously.
• FIG. 18A illustrates a skin region 800 with a treated region 802 that contains a photoresponsive material.
• photoresponsive material may be delivered to region 802 topically, by injection, or systemically.
• step 18 B patterned light is delivered to area 804 in region 802 through the use of a stencil or mask or other methods as described herein below. Patterned light causes a reaction or transformation of photoresponsive material in area 804 , to produce a pattern 806 of modified material as shown in FIG. 18C .
• an additional step may be carried out to remove unmodified photoresponsive material from skin region 800 , so that only pattern 806 remains in skin region 800 , as depicted in FIG. 18D .
• FIGS. 19A-19C Several methods may be used to expose a treated skin region to patterned light.
• a mask (or stencil) 850 may be placed on the skin surface to block exposure of the skin surface to light except in the areas that are to be patterned.
• FIG. 19A depicts a mask 850 having an opaque portion 852 and a light transmitting portion 854 .
• Mask 850 may be placed over a skin region that contains a photoresponsive material.
• the skin region is a portion of the arm 858 of a subject.
• a drape 860 may be used to extend the covered area of arm 858 ; various functionally equivalent configurations may be devised by a practitioner of skill in the relevant art.
• Light from light source 862 may cover all of the light transmitting portion 854 of mask 850 , as depicted in FIG. 19B .
• light from a light source may cover a portion of a light transmitting portion of a mask, and the light source may be moved to one or more additional regions in order to expose all of the skin region exposed by the light transmitting portion of the mask.
• Light source 862 may be removed or turned off following exposure to light for a period of time sufficient to produce a desired modification of the photoresponsive material, and mask 830 and drape 860 (if used) removed.
• arm 858 of the subject bears a patterned distribution 864 of modified photoresponsive material that corresponds to the light transmitting regions 854 of mask 850 .
• a photoresponsive material is delivered to at least a skin region of a subject.
• a mask is placed over the skin region, the mask including one or more light blocking regions and defining one or more light transmissive regions to form a pattern.
• the skin region is exposed to light of wavelength band, time-averaged flux and/or fluence sufficient to produce modification of the photoresponsive material within the skin region beneath the one or more light transmissive regions defined by the mask.
• Delivering a photoresponsive material may include delivering a photoresponsive material that is converted from an active form to an inactive form by exposure to light.
• delivering a photoresponsive material may include delivering a photoresponsive material that is converted from an inactive form to an active form by exposure to light.
• the method may also include reversing the photo reaction by exposing the skin region to light of a wavelength band, time-averaged flux and/or fluence sufficient to reverse the reaction.
• Photo reactions that may operate in a first direction at a first wavelength band, time-averaged flux and/or fluence, and which may be reversed at a second wavelength band, time-averaged flux and/or fluence include, for example crosslinking of PEG-cinnamylidine acetate as described in U.S. Pat. No. 5,990,193, and reactions of various aromatic diazo dyes, as described in U.S. Pat. No. 5,998,588, both of which are incorporated herein by reference in their entirety.
• FIGS. 21A and 21B An alternative method of delivering patterned light is depicted in FIGS. 21A and 21B .
• FIG. 21A depicts a light source 880 that produces patterned light 882 . This may be accomplished by placing a mask over a single light source of sufficient size and capable of generating substantially collimated light, or by placing multiple smaller light sources, also capable of producing relatively parallel light, in a suitable arrangement. Patterned light 882 from light source 880 may then be delivered to a treated surface 884 . In the example of FIG. 21A , treated surface 884 need not be masked, because the light is patterned, although in some embodiments patterned light may be used in combination with a mask or stencil.
• FIG. 21B illustrates pattern 886 that has been formed by modification of photoresponsive material in or on treated surface 884 by exposure to patterned light 882 .
• Delivering photoresponsive material to at least a skin region may be further characterized as delivering photoresponsive material topically (step 902 a ), delivering photoresponsive material by injection in the skin region ( 902 b ) by delivering photoresponsive material by injection below the stratum corneum with a microneedle array ( 902 c ), or delivering the photoresponsive material systemically ( 902 d ).
• Delivering targeted light to the skin region according to a pattern may be performed by a number of approaches, including delivering targeted light to a plurality of locations in the skin region according to a pattern ( 904 a ), delivering targeted light to the skin region according to a decorative pattern (step 904 b ) or delivering targeted light to the skin region according to a pattern corresponding to one or more structures in the skin region (step 904 c ).
• Methods including step 904 c may also include a step of detecting one or more features in the skin region.
• the target light may have a wavelength content, time-averaged flux, or fluence sufficient to cause a transformation of the photoresponsive material to a modified form.
• a photoresponsive material may be introduced into a skin region in a patterned distribution, and light delivered to the skin in a relatively non-targeted fashion in order to cause transformation of the photoresponsive material to a modified form.
• a photoresponsive material may be delivered topically in a pattern by various methods, including painting, printing (i.g., ink jet or wire jet printing), and stenciling, for example.
• Photoresponsive material may be delivered into the skin, below the skin surface, by injection with one or multiple needles (e.g. tattoo needles, micro-needle array, hypodermic needle) or by a pressure jet.
• FIG. 23A illustrates a skin region 950 including a patterned distribution of photoresponsive material 952 .
• light source 954 is used to deliver light to a region 956 which includes patterned distribution of photoresponsive material 952 .
• Light source 954 delivers light in a relatively non-targeted fashion; any light distribution that covers patterned distribution of photoresponsive material 952 with light of sufficient intensity or fluence may be used.
• light may be delivered in several stages or from several sources, e.g., by delivering light from two or more sources, or from the same source at two different times, such that each individual delivery of light covers only a part of the patterned distribution of photoresponsive material, but that together, the multiple deliveries of light cover the entire patterned distribution of photoresponsive material.
• FIG. 23C following modification of photoresponsive material due to light exposure, a patterned distribution of modified material 958 is present in skin region 950 .
• both photoresponsive material and light may be delivered to the skin in a pattern.
• Patterned delivery of photoresponsive material and of light may be accomplished by any of the exemplary methods described herein above, for example.
• the patterns may be substantially similar and overlapping, in which case the distribution pattern of the modified form in or on the skin will be substantially the same as the distribution patterns of the unmodified form and the light. If the distribution pattern of the photoresponsive material and the distribution pattern of the light are partially overlapping, a patterned distribution of the modified form may be obtained that is defined by the shape and distribution of the regions of overlap between the distribution patterns of photoreactive material and light. This approach is illustrated in FIG. 24 and FIGS. 25A-25C . At step 972 of FIG.
• a photoresponsive material is delivered to a skin region of a subject in a first pattern.
• photoresponsive material is delivered to the skin region topically.
• photoresponsive material 972 b is delivered to the skin region by injection (e.g., via a hypodermic needle, tattoo needle, microneedle array, pressure jet, etc.)
• targeted light is delivered to the skin region in a second pattern, the second pattern overlapping partially with the first pattern.
• the photoresponsive material in the areas of overlap between the first pattern and the second pattern may undergo photomodification to form an overlap pattern of modified photoresponsive material within the skin region. The method is illustrated in graphic form in FIGS. 25A-25C . In FIG.
• a patterned distribution of photoresponsive material 1000 is formed in skin region 1002 .
• patterned distribution of photoresponsive material 1000 includes five lines of photoresponsive material 1000 a , 1000 b , 1000 c , 1000 d , and 1000 e .
• Such a patterned distribution may be formed by printing, injection, or other methods as described herein or as may be devised by one of skill in the art.
• a patterned distribution of light 1004 is delivered to skin region 1002 , overlapping patterned distribution of photoresponsive material 1000 .
• FIG. 26 is a block diagram of a system 1050 that includes an imaging device 1052 .
• System 1050 may include a light source 1054 capable of producing light of at least one defined wavelength band, memory 1056 capable of storing a pattern in machine-readable form representing a plurality of locations within a skin region to which light from the light source is to be directed, controllable positioning system 1060 configured to adjust the positioning of light from light source 1054 on a skin region, one or more optical components 1062 capable of focusing light from the light source 1054 at a specific depth within a skin region in response to a control signal, and controller 1064 configured to generate a control signal 1066 for driving controllable positioning system 1060 to direct light onto a plurality of skin locations according to the pattern 1058 stored in memory 1056 .
• a light source 1054 capable of producing light of at least one defined wavelength band
• memory 1056 capable of storing a pattern in machine-readable form representing a plurality of locations within a skin region to which light from the light source is to be directed
• controllable positioning system 1060 configured to adjust the positioning of light from light source 1054 on a skin region
• controller 1064 may be configured to generate control signal 1066 for driving optical components 1062 to adjust the focusing of light at different depths and at different skin locations according to pattern 1058 stored in memory 1056 .
• controllable positioning system 1060 includes one or more controllable deflectors configured to aim light from light source 1054 , wherein the position of at least one of the deflectors is controllable to aim light toward any of the plurality of skin locations.
• System 1050 may also include one or more I/O devices 1068 to provide for entry of control inputs by a user and for the presentation of information or data to the user.
• Controller 1064 may include one or more of hardware, software, and firmware. In some embodiments, controller 1064 may include a microprocessor. System 1050 may include an imaging device, which may be, for example, a CCD camera.
• photoresponsive materials may be delivered to at least a skin region of a subject, and some or all of the photoresponsive material may be exposed to light to cause a reaction or conversion of the photoresponsive material.
• Unwanted material may be removed by processes normally occurring in the body, such as metabolism or excretion of the material, or by sluffing of skin containing the material.
• materials may not be removed by naturally occurring processes, or may not be removed as quickly as is deemed desirable, and further treatment steps may be used to remove the materials form the body.
• unmodified material may be removed, while modified material may be left in the skin region.
• modified material may be removed from the skin region after a use period.
• Treatment to removed either modified or unmodified photoresponsive material, or both may include phototreatment (e.g., photobleaching), chemical treatment (e.g., chemical bleaching), chemo-mechanical treatment, or treatment by exposure to heat, vibration, electromagnetic fields, among others.
• FIG. 27 depicts an exemplary sequence of method steps.
• a photoresponsive material is delivered to at least a skin region of a subject.
• a mask is placed over the skin region, the mask including one or more light blocking regions and defining one or more light transmissive regions to form a pattern.
• the skin region may be exposed to light of wavelength band, time-averaged flux and/or fluence sufficient to produce modification of the photoresponsive material within the skin region beneath the one or more light transmissive regions beneath the mask.
• Method steps 1102 through 1106 correspond to the method illustrated in FIGS. 19A-19C , for example.
• the modification is reversed by exposing the skin region to light of wavelength, time-averaged flux and/or fluence sufficient to reverse the modification.
• the modified form may include removal of the modified form of the photoresponsive material from the skin region over time.
• the modified form may be removed from the skin region by metabolism.
• the modified form may be removed from the skin region through sluffing of dead skin cells and/or the continual shedding of epidermal outer layers, for example.
• the modified form may be removed from the skin region after a treatment period.
• the method may include removing the modified form by a photo treatment, by a chemical treatment, or by a chemo-mechanical treatment.
• FIG. 28 depicts steps of a method that includes removing the modified form of the photoresponsive material from the skin region after a treatment period.
• a photoresponsive material is delivered to at least a skin region of a subject.
• targeted light is delivered to the skin region according to a pattern, the targeted light having a wavelength content, time-averaged flux and/or fluence sufficient to cause a transformation of the photoresponsive material to a modified form.
• the modified form is removed from the skin region after a treatment period.
• the modified form may be removed by photo treatment (step 1156 a ) or by chemical treatement ( 1156 b ), for example.
• the treatment period may be quite brief, producing only a transient presence of the modified material in the system, or may be of extended duration, of hours, days, weeks, months, or even years.
• photoresponsive materials examples include, but are not limited to photodynamic therapy agents, photochromic dyes and pigments, photo-crosslinkable materials, photopolymerizable materials, and photodimerizable materials, luminides, light reactive polymers that change in conformation, volume, binding activity, drug activity, hydrogels of various types.
• photoresponsive materials may be cosmetic materials having selected color or other appearance properties. Reaction undergone by photoresponsive materials may be a reversible transformation or an irreversible transformation.
• the transformation may convert the photoresponsive material from an active to an inactive form. In other embodiments, the transformation may convert the photoresponsive material from an inactive to an active form.
• the transformation may include, for example, conversion of a photoresponsive material from a substantially colorless form to a colored form, or from a colored form to a substantially colorless form. Examples of photochromic dyes are listed in U.S. Pat. No. 6,602,975, which is incorporated herein by reference.
• the transformation may include conversion of the photoresponsive material from a first color to a second color, or may modify the extent to which it scatters light of a given waveband.
• the modified form may be visible under natural light in some embodiments. In some embodiments, the modified form may be visible under ultraviolet light. In some embodiments, the modified form may be fluorescent.
• the modified form may be a pigment, dye, pharmaceutical compound, or cosmetic material.
• FIG. 29 depicts steps of a method that includes removing unmodified photoresponsive material from a skin region of a subject.
• a photoresponsive material is delivered to at least a skin region of a subject.
• targeted light is delivered to the skin region according to a pattern, the targeted light having a wavelength content, time-averaged flux and/or fluence sufficient to cause a transformation of the photoresponsive material to a modified form.
• the unmodified photoresponsive material is removed from the skin region.
• the unmodified photoresponsive material may be removed by phototreatment, as shown in step 1206 a , or by chemical treatment, as shown in step 1206 b.
• FIG. 30 illustrates a method of providing controlled delivery of an active compound to a skin region, which includes delivering an inactive chemical compound non-specifically to at least a skin region of a subject at step 1252 and exposing the skin region to targeted light delivered to multiple selected locations within the skin region to form a pattern at step 1254 , the targeted light having a wavelength band, time-averaged flux and/or fluence sufficient to cause modification of the inactive chemical compound to form an active compound within the skin region at the selected locations according to the pattern.
• delivering an inactive chemical compound may include delivering an inactive form of a photodynamic therapy agent or a photochromic dye or pigment. It is within the present inventive scope to deliver two-or-more materials in this manner, and to induce reactions between the two-or-more of them or between the two-or-more of them and ambient materials by the action of the incident light.
• Systems for the delivery of light to skin may include various types of light sources.
• light sources must deliver light having wavelength content, fluxes and fluences sufficient to produce a particular effect in the photoresponsive material that is being exposed to the light.
• the light may have a wavelength content, time-averaged flux and/or fluence sufficient to cause a photo cross-linking reaction of the photoresponsive material.
• the light may have wavelength content, time-averaged flux and/or fluence sufficient to cause a photochromic reaction of the photoresponsive material.
• the light may have a wavelength content, time-averaged flux and/or fluence sufficient to cause a photodimerization reaction of the photoresponsive material.
• Light sources suitable for use in various embodiments as described herein include lasers, laser diodes, as well as various non-coherent light sources.
• Light sources may include light emitting diodes.
• light sources may emit light in an ultraviolet wavelength band.
• light sources may emit light in a visible wavelength band, or in an infrared one. Broad-band light sources may be used in some embodiments.
• FIG. 31 depicts a method of manufacturing a targeted light delivery system.
• Step 1302 includes providing a housing configured to be positioned relative to a skin region of a subject.
• a light source is mounted in fixed relationship with respect to the housing, the light source capable of delivering light of a wavelength band, time-averaged flux and/or fluence sufficient to activate a photoresponsive material in a skin region when the housing is positioned realitive to the skin region.
• a controllable optical system is mounted with respect to the housing and the light source such that light from the light source may be focused on a skin region by the controllable optical system when the housing is positioned relative to the skin region.
• driver interface circuitry is connected to the light source and the controllable optical system, the driver interface circuitry adapted to receive one or more control signals and responsive to the control signals to drive the controllable optical system and the light source to focus light on one or more targets in the skin region according to a pattern and/or in an aligned manner.
• FIG. 32 depicts a method of manufacturing a device for delivering patterned light.
• a housing is provided that is configured to be positioned adjacent to a skin region of a subject.
• a light source is mounted in fixed relationship with respect to the housing, the light source capable of delivering light of a wavelength band, time-averaged flux and/or fluence sufficient to activate a photoresponsive material in a skin region when the housing is positioned adjacent to the skin region.
• a controllable optical system is mounted with respect to the housing and the light source such that light from the light source may be focused on a skin region by the controllable optical system when the housing is positioned relative to the skin region at step 1356 .
• driver interface circuitry is connected to the light source and the controllable optical system, the driver interface circuitry adapted to receive one or more control signals from a microprocessor-based controller and responsive to the control signals to drive the controllable optical system and the light source to focus light on one or more locations in the skin region according to a pattern.
• software code is provided that is executable by the microprocessor based controller to generate the one or more control signals.
• the driver interface circuitry may be adapted to receive the one or more control signals from a microprocessor-based controller.
• the method may include providing software code executable by the microprocessor-based controller to generate the one or more control signals.
• FIG. 33 depicts features of a device as described in connection with FIG. 32 ; included are housing 1400 , light source 1402 , controllable optical system 1404 , and driver interface circuitry 1406 .
• Driver interface circuitry receives at least one control signal 1408 on input 1410 , and generates control signals 1412 and 1414 for driving light source 1402 and controllable optical system 1404 , respectively.
• Portion 1416 of housing 1400 may be configured to be positioned adjacent a skin region 1418 , so that light 1420 may be directed to skin region 1418 by controllable optical system 1404 .
• lithography of silicon wafers may be modified and combined in a variety of ways analogous to those of photolithography of silicon wafers.
• masks or stencils may be used to form positive or negative patterns.
• Additive and subtractive processing may be performed by appropriate combinations of steps. For example, multiple steps, each involving the use of a different stencil and a different depth of focus of light in the skin, may be used to form a patterned distribution of material that varies as a function of depth within the skin.
• a multi-step process may be used in which a material modified at a first step, for example by treatment at a first wavelength, may in turn influence (e.g.
• an implementer may opt for a hardware and/or firmware vehicle; alternatively, if flexibility is paramount, the implementer may opt for a solely software implementation; or, yet again alternatively, the implementer may opt for some combination of hardware, software, and/or firmware.
• any vehicle to be utilized is a choice dependent upon the context in which the vehicle will be deployed and the specific concerns (e.g., speed, flexibility, or predictability) of the implementer, any of which may vary.
• those skilled in the art will recognize that optical aspects of implementations will require optically-oriented hardware, software, and or firmware.
• signal bearing media include, but are not limited to, the following: recordable type media such as floppy disks, hard disk drives, CD ROMs, digital tape, and computer memory; and transmission type media such as digital and analog communication links using TDM or IP based communication links (e.g., links carrying packetized data).
• electrical circuitry includes, but is not limited to, electrical circuitry having at least one discrete electrical circuit, electrical circuitry having at least one integrated circuit, electrical circuitry having at least one application specific integrated circuit, electrical circuitry forming a general purpose computing device configured by a computer program (e.g., a general purpose computer configured by a computer program which at least partially carries out processes and/or devices described herein, or a microprocessor configured by a computer program which at least partially carries out processes and/or devices described herein), electrical circuitry forming a memory device (e.g., forms of random access memory), and/or electrical circuitry forming a communications device (e.g., a modem, communications switch, or optical-electrical equipment).
• a computer program e.g., a general purpose computer configured by a computer program which at least partially carries out processes and/or devices described herein, or a microprocessor configured by a computer program which at least partially carries out processes and/or devices described herein
• electrical circuitry forming a memory device
• systems as described herein may include one or more of a memory such as volatile and non-volatile memory, processors such as microprocessors and digital signal processors, computational-supporting or -associated entities such as operating systems, user interfaces, drivers, sensors, actuators, applications programs, one or more interaction devices, such as data ports, control systems including feedback loops and control implementing actuators (e.g., devices for sensing position and/or velocity and/or acceleration or time-rate-of-change thereof; control motors for moving and/or adjusting components).
• a skin treatment system may be implemented utilizing any suitable available components, combined with standard engineering practices.
• any two components herein combined to achieve a particular functionality can be seen as “associated with” each other such that the desired functionality is achieved, irrespective of architectures or intermediate components.
• any two components so associated can also be viewed as being “operably connected”, or “operably coupled”, to each other to achieve the desired functionality.

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