System for conforming treatment applicator to non-uniform surface

Abstract

To provide a system and a method for delivering therapy using an applicator guide and a plurality of catheters for delivering, e.g., radiation, drug, RF, laser or ultrasound therapy.SOLUTION: An applicator guide 11 includes through hole channels 18 through which catheters 12 may be introduced. The through hole channels 18 may be sized so that the plurality of catheters 12 may freely and independently traverse the through hole channels. By positioning the applicator guide 11 over a target area of a patient's skin, the catheters 12 are free to make contact with the patient's skin and conform to any contours of the patient's skin. The catheters 12 may be microneedles that may be locked in the conformed orientation, so that the microneedles may non-invasively penetrate the patient's skin to deliver the therapy transdermally. The applicator guide 11 may be coupled to an after-loader 14, a drug reservoir, a pulse generator, and / or a power generator controlled by a healthcare provider via a computing device 15.SELECTED DRAWING: Figure 1A

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims priority to U.S. Provisional Patent Application No. 62 / 937,216, filed November 18, 2019, the entire contents of which are hereby incorporated by reference herein.

[0002] The disclosure relates to systems and methods for improving the application of a treatment applicator to a non-uniform patient surface. [Background technology]

[0003] Skin cancer is the most common type of cancer in the United States, with an annual incidence of over 5 million cases. Basal cell carcinoma (BCC) and squamous cell carcinoma (cSCC) account for over 95% of all skin cancer diagnoses.

[0004] A variety of therapeutic options are currently available to treat skin cancer. Some of the most common treatment approaches include surgical excision, cryotherapy, radiation therapy, and topical agents. Surgical excision is considered the "gold standard" for the curative treatment of BCC and cSCC. While excision may be the preferred approach, it is often painful and can result in disfigurement. Cryotherapy and topical agents have limited application and success rates.

[0005] Radiation therapy plays an important role in the treatment of skin cancer in both definitive and adjuvant settings. One form of radiation delivery that can be used in skin cancer treatment is brachytherapy. Brachytherapy generally involves placing a radioactive substance adjacent to the treatment target via an applicator. Brachytherapy can involve an interstitial procedure or can be used to treat the surface of a patient's skin without entering the patient's body.

[0006] Current superficial brachytherapy (also translated as "brachytherapy") treatment systems are administered using either prefabricated, shielded, fixed-geometry applicators or custom-made applicators made from thermoplastic materials. Current systems typically involve multi-channel catheters that run parallel to the surface of the skin. Because the radioactive material must run through these channels to reach the target tissue, the channels are limited in their geometry. Channels can also be shaped to fit the contours of the patient's face, but this process is expensive and time-consuming.

[0007] In addition, other types of skin-based diseases may require a drug delivery system to effectively administer drug therapy to patients. For example, topical dermatological preparations such as foams, creams, lotions, gels, etc. are commonly used to target skin-based diseases. However, many drug molecules are too large or too lipophobic to penetrate the stratum corneum (SC) barrier, which is the outermost layer of the skin. The hydrophobic lipids in the SC can block the entry of most topically applied drugs. Therefore, such drugs may need to be delivered beyond the epidermis into the dermis or deeper.

[0008] Transdermal drug delivery systems (TDDS), which use the skin as the primary route of drug delivery, have been shown to offer advantages over topical and intravenous drug delivery routes. TDDS are noninvasive and painless, and advantageously deliver drugs effectively without the need for frequent administration to maintain consistent drug delivery.

[0009] U.S. Patent Nos. 7,658,728, 7,785,301, and 8,414,548 describe microneedle patches for transdermal drug delivery, such as the AdminPatch® microneedle array (available from nanoBioSciences, LLC, Sunnyvale, California). These patches are static devices used to create micropores in the outermost layer of the skin and therefore do not conform to the concave or convex features of the skin. The application and delivery of these drugs is crucial to the effectiveness and satisfactory outcome of the treatment. [Prior art documents] [Patent documents]

[0010] [Patent Document 1] U.S. Patent No. 7,658,728 [Patent Document 2] U.S. Patent No. 7,785,301 [Patent Document 3] U.S. Patent No. 8,414,548 Summary of the Invention [Problem to be solved by the invention]

[0011] In view of the above-described shortcomings of known systems and methods for applying radiation therapy and other treatments (e.g., drugs, ultrasound, RF, laser, etc.) to contoured and non-uniform patient surfaces, it would be desirable to provide systems and methods for precisely applying therapy to a patient's non-uniform skin. It would further be desirable to provide systems and methods for applying therapy to dynamic skin surfaces.

[0012] Additionally, it would be desirable to provide a system and method for transdermal application of therapy to a dynamic skin surface. [Means for solving the problem]

[0013] The present invention is directed to a radiation therapy system having an applicator guide with multiple through-hole channels through which multiple catheters can be positioned. When the applicator guide and catheters are positioned over a non-uniform portion of a patient's anatomy, the catheters can move freely and independently within the through-hole channels and conform to the patient's skin. The catheters may be connected via transfer tubing to an afterloader that delivers a radiation source through the catheters. A healthcare provider using a computing device may control the afterloader.

[0014] In accordance with the principles of the present disclosure, one exemplary radiation therapy system may include an applicator guide having a plurality of through-hole channels extending from a first side of the guide structure to a second side of the guide structure. The plurality of through-hole channels may be formed in an array. A plurality of catheters configured to deliver radiation treatments may be disposed in respective through-hole channels within the applicator guide. The plurality of catheters are independently and freely movable within their respective through-hole channels and are movable in response to contact of distal tips of the plurality of catheters with an area of the patient's skin, such that the distal tips independently move to conform to the contours of and contact the area of the patient's skin. The plurality of catheters may be configured to selectively deliver radiation treatments to target areas within the area of the patient's skin while the plurality of catheters are positioned in an aligned orientation.

[0015] An exemplary method for administering radiation therapy to a patient according to the principles of the present disclosure may include positioning an applicator guide over a target area of the patient and aligning a plurality of catheters with the target area of the patient. The applicator guide may include a plurality of through-hole channels into which a catheter of the plurality of catheters is respectively loaded. The plurality of catheters are independently and freely movable within respective through-holes of the plurality of through-holes, and are movable in response to contact of distal tips of the plurality of catheters with the target area of the patient, such that the distal tips move independently to match the contours of the target area of the patient. The method may ultimately include delivering radioactive material to at least one of the plurality of catheters.

[0016] One exemplary system for administering radiation therapy to a non-uniform portion of a patient's skin in accordance with the principles of the present disclosure may include an applicator assembly, an afterloader connected to each of a plurality of catheters via a plurality of transfer tubes, and a computing device in communication with the afterloader and configured to instruct the afterloader to deliver radioactive material to the plurality of catheters.

[0017] The applicator assembly may include an applicator guide configured to maintain the multiple catheters in an upright position and multiple catheters configured to deliver radiation treatments. Each of the multiple catheters is independently and freely movable relative to the applicator guide and each other, and is movable in response to contact of distal tips of the multiple catheters with an area of the patient's skin, such that the distal tips move independently to conform to the contours of and contact the area of the patient's skin. Further, the multiple catheters may be configured to selectively deliver radiation treatments to target areas within the area of skin while the multiple catheters are positioned in the aligned orientation.

[0018] According to another aspect of the present disclosure, another exemplary therapy delivery system is provided. The system may include an applicator guide having a plurality of through-hole channels extending from a first side of the applicator guide to a second side of the applicator guide, the plurality of through-hole channels being arranged in an array. The system may further include a plurality of catheters for delivering therapy, each catheter disposed in a respective one of the plurality of through-hole channels in the applicator guide. The plurality of catheters are independently and freely movable within their respective through-hole channels with at least one degree of freedom, such that the plurality of catheters can conform to the contours of an area of skin of a patient and contact the area in a conforming orientation. Thus, while the plurality of catheters are positioned in a conforming orientation, the plurality of catheters can deliver therapy to at least a portion of the area of skin of the patient.

[0019] The multiple catheters may include multiple microneedles sized and shaped to non-invasively penetrate the stratum corneum (SC) of the patient's skin, such that the multiple microneedles selectively deliver a therapy percutaneously to at least a portion of the area. For example, the applicator guide may include multiple locks, each of which may be operatively coupled to each of the multiple microneedles to lock each of the multiple microneedles in a coordinated orientation. In this manner, the multiple microneedles may non-invasively penetrate the stratum corneum (SC) of the patient's skin in a coordinated orientation. The multiple locks may be activated individually or simultaneously.

[0020] In some embodiments, the plurality of microneedles can selectively deliver a drug transdermally to at least a portion of an area. For example, the plurality of microneedles can be coated with a drug. Additionally or alternatively, the plurality of microneedles can include an internal lumen, such that the drug is delivered transdermally to at least a portion of the area through the internal lumen of the plurality of microneedles. Additionally or alternatively, the drug can be embedded within the plurality of microneedles, such that at least a portion of the plurality of microneedles degrades to deliver the drug transdermally to at least a portion of the area.

[0021] In some embodiments, the multiple catheters may be operatively coupled to a pulse generator to selectively deliver RF energy to at least a portion of the area. In some embodiments, the multiple catheters are operatively coupled to an ultrasound transducer to selectively deliver ultrasound energy to at least a portion of the area. In some embodiments, the multiple catheters are operatively coupled to an afterloader to selectively administer radiation therapy to at least a portion of the area. For example, each catheter of the multiple catheters may be individually activated to deliver radiation. The afterloader may be connected to each of the multiple catheters via multiple delivery tubes. Accordingly, the system may further include a computing device in communication with the afterloader and capable of instructing the afterloader to deliver radioactive material to the multiple catheters. Additionally, one or more of the multiple catheters may simultaneously apply heat while administering therapy to the target area.

[0022] According to another aspect of the present disclosure, another exemplary method for administering therapy to a patient is provided. The method may include positioning an applicator guide over a target area of the patient, loading a plurality of catheters into the through-hole channels of the plurality of through-hole channels such that each of the plurality of through-hole channels is loaded with a catheter of the plurality of catheters, aligning the plurality of catheters in an aligned orientation with the target area of the patient, and administering therapy to the target area of the patient via at least one of the plurality of aligned catheters.

[0023] The method may further include locking the microneedles in an aligned orientation. Additionally, the method may include penetrating a stratum corneum (SC) of the patient's skin with the plurality of aligned microneedles, such that administering therapy to a target area of the patient includes administering therapy to the target area of the patient transcutaneously. [Brief explanation of the drawings]

[0024] [Figure 1A] 1 depicts a radiation therapy system including an afterloader, an applicator guide, and a computing device running afterloader software. [Figure 1B] 1 depicts an exemplary applicator guide positioned on a patient's face. [Figure 2] FIG. 1 is a schematic diagram of exemplary electronics and hardware components of a computing device. [Figure 3A] FIG. 1 is a perspective view of an example applicator guide. [Figure 3B] FIG. 10 is a side cross-sectional view of an example applicator guide. [Figure 3C] FIG. 10 is a top view of an example applicator guide. [Figure 4A] FIG. 1 is a perspective view of an exemplary applicator guide loaded with a catheter. [Figure 4B]FIG. 1 is a perspective view of an exemplary applicator guide loaded with a catheter and a tungsten insert. [Figure 5] 1 is a cutaway view of an example applicator guide having a stopper attached and positioned thereon. FIG. [Figure 6A] 10 depicts a side view of an example applicator guide with an example guide extender. [Figure 6B] 10 depicts a top view of an example applicator guide with an example guide extender. [Figure 7] 1 illustrates an example applicator guide with a guide extender having a spring and loaded with a catheter. [Figure 8] 1 illustrates an example applicator guide with a guide extender having a sensor and loaded with a catheter. [Figure 9] 1 illustrates an exemplary applicator guide coupled to a table mount and positioned over a patient's face. [Figure 10] 1 illustrates an exemplary applicator guide coupled to a head mount and positioned over a patient's face. [Figure 11] FIG. 1 is a cutaway view of an example catheter having a heater. [Figure 12] FIG. 1 is a perspective view of an exemplary applicator guide loaded with microneedles. [Figure 13] 1 depicts a therapeutic system for transdermal drug delivery that includes a drug reservoir, an applicator guide, and a computing device. [Figure 14] 1 depicts a therapy system for delivering RF energy, the therapy system including a pulse generator, an applicator guide, and a computing device. [Figure 15] 1 depicts a therapy system including an ultrasound transducer, an applicator guide, and a computing device for delivering ultrasound energy. [Figure 16] 1 depicts a therapy system including a laser energy source, an applicator guide, and a computing device for delivering laser energy. DETAILED DESCRIPTION OF THE INVENTION

[0025] These and other features of the present disclosure will become apparent from the following description and appended claims, taken in conjunction with the accompanying drawings, in which the disclosure will be described with more particularity and detail through the use of the accompanying drawings, with the understanding that these drawings depict only a few embodiments in accordance with the disclosure and therefore should not be considered as limiting the scope of the disclosure.

[0026] The disclosed systems include systems and methods for delivering and guiding applicators, such as radiotherapy applicators, or microneedles over non-uniform surfaces in a manner that allows the catheter to conform to curved and even dynamic surfaces. The systems may further include multiple catheters, transfer tubing, an afterloader for delivering radioactive material or a drug reservoir for administering drug therapy or an energy source for delivering energy, along with an applicator guide.

[0027] To administer radiation therapy to a patient's skin target, multiple catheters can be positioned through the applicator guide, and the computing device can control an afterloader to deliver the radiation source through a transfer tube to a pre-specified location within the catheter, such as to a tip, which may be cylindrical and / or have a flat cap.

[0028] Referring to FIG. 1A, a radiation therapy system 10 is depicted. The radiation therapy system 10 may include an applicator guide 11, a catheter 12, a transfer tube 13, an afterloader 14, and a computing device 15. As shown in FIG. 1A, the catheter 12 may be positioned entirely through the applicator guide 11 via a through-hole 18 and coupled to the transfer tube 13 at a connection interface 16. The transfer tube 13 may further connect to the afterloader 14 at the connection interface 16. The computing device 15 may be a stand-alone computing device or may be incorporated into the afterloader 14. The computing device 15 may communicate with the afterloader 14 via any known wired or wireless connection (e.g., Bluetooth®, Wi-Fi Direct™, etc.).

[0029] 1B, applicator guide 11 is depicted positioned over a patient to administer radiation therapy via catheter 12. Catheter 12 extends through applicator guide 11 and rests on the patient's surface. Catheter 12 is free to move within applicator guide 11, so that it will adapt to the contours and curvatures of the patient's body (e.g., face) and will even adapt to conform to surface variations. Specifically, catheter 12 is oriented in a downward direction and will move downward due to gravity. When catheter 12 contacts the patient, it experiences an opposing upward force, causing it to conform to the patient's surface.

[0030] Once the catheter 12 is aligned with the surface of the patient's body and the applicator guide is reproducibly secured in place, a planning computed tomography (CT) scan is performed through the applicator and the skin target to generate a CT data set. This CT data set will be used to generate a conformal radiation plan for treating the skin target. A radiation oncologist and medical physicist can adjust the radiation dose and treatment time using the computing device 15 to control the afterloader 14 to deliver the appropriate amount of radiation treatment to the patient. The radiation plan will be approved by the radiation oncologist. A healthcare professional will activate the afterloader 14 via the computing device 15 to deliver the radioactive material through the transfer tube 13 to a location within the catheter 12, such as the tip.

[0031] 2, there is shown an exemplary functional block diagram representing hardware and software components of computing device 15. The hardware and software components of computing device 15 may include one or more processing units 21, memory 22, storage 27, communication units 23, and power sources 26, as well as input devices 24 and output devices 25. Computing device 15 may be in communication with the Internet and / or other computing devices.

[0032] The processing unit 21 may be one or more processors configured to run an operating system 28 and / or an afterloader application 29. The afterloader application 29 running on the processing unit 21 may be adapted to control the operation of the afterloader 14 or otherwise provide oversight of the operation and behavior of the afterloader 14. The afterloader application 29 may be stored in the storage 27 and adapted to be executed on the processing unit 21. The afterloader application 29 may be a software application and / or software module having one or more instruction sets suitable for performing the operations of the controlling computing device 15 described herein.

[0033] Computing device 15 may optionally run an operating system 28 that is stored in storage 27 and executed on processing unit 21. Operating system 28 is adapted to control the overall operation of computing device 15 and may cooperate with afterloader application 29 to implement the functionality of computing device 15 described herein. Computing device 15 may also optionally run graphics libraries, other operating systems, and / or any other application programs.

[0034] The memory 22 may include, but is not limited to, volatile memory (e.g., random access memory (RAM)), non-volatile memory (e.g., read-only memory (ROM)), flash memory, or any combination thereof. The communication unit 23 may send and receive information to and from other computing and / or peripheral devices. The communication unit 23 may be any known communication infrastructure facilitating communication via any known wired or wireless connection, including any known standard, such as any IEEE 802 standard. The power source 26 may be a battery or any other external power source. The storage 27 may include, but is not limited to, removable and / or non-removable storage, such as, but not limited to, a magnetic disk, an optical disk, or tape.

[0035] Input device 24 may be one or more devices coupled to or incorporated within computing device 15 for inputting data into computing device 15. Input device 24 may include, for example, a keyboard, a mouse, a pen, a voice input device (e.g., a microphone), a touch input device (e.g., a touchpad or touchscreen), and / or a camera. Output device 25 may be any device coupled to or incorporated within computing device 15 for outputting or otherwise displaying data (e.g., a display, a speaker, a printer, etc.).

[0036] It will of course be understood that computing device 15 may include additional or fewer components than those depicted in FIG. 2, or may include more than one of each type of component.

[0037] 3A-3C, an applicator guide 11 is depicted. The applicator guide 11 may be rectangular or may have a plurality of through-holes 31 and through-hole channels 32 formed in an array extending through the entire length of the applicator guide 11, as shown in FIG. 3B. The applicator guide 11 may be hollow or may be solid with through-holes extending therethrough. The applicator guide 11 may have various width W, length L, and height H dimensions and proportions different from those shown in FIG. 3A while still achieving the functionality described herein. The applicator guide 11 has a height H that is large enough to maintain the catheter 12 in an upright orientation, as shown in FIG. 1B.

[0038] While the applicator guide 11 is shown in FIG. 3A as having a rectangular shape, it is understood that the applicator guide 11 can have any other shape, such as a circular or asymmetrical body. The through-holes 31 may have a circular cross-section with a constant radius. The radius may be sized so that the catheter 12 fits within the through-hole channels 38 with sufficient clearance to move freely along the through-hole channels 38. The through-hole channels 38 may have a smooth surface to reduce friction, or may even be lined along a portion or the entire length of the through-hole channels 38 with a material different from the applicator guide 11 to further reduce friction against the catheter 12. Alternatively, the through-hole channels 38 may vary in radius or even shape. For example, the through-hole channels 38 may have a conical shape with a narrowing at one end. The applicator guide 11 may optionally include a lock in one or more of the through-hole channels to lock the catheter in a specific position within the through-hole channels. For example, the locks may include screws or other protrusions that extend into the through-hole channel and contact the catheter to prevent the catheter from moving within the through-hole channel. The locks may be activated in unison or individually.

[0039] The arrangement of the through-holes 31 extending through the applicator guide 11 may follow the generally uniform pattern depicted in the top view of the applicator guide 11 shown in FIG. 3C. The through-holes may be closer together or further apart than shown in FIG. 3C. Alternatively, the arrangement of the through-holes 31 may follow a different or non-uniform pattern than that shown in FIG. 3C. Furthermore, the through-holes 31 may vary in diameter and even shape to accommodate catheters 12 of different shapes or sizes. For example, the through-holes 31 near the center of the applicator guide 11 may have a larger diameter than the through-holes 31 located near the periphery of the applicator guide 11. In yet another alternative arrangement, the through-holes 31 may be spaced closer together near the center of the applicator guide 11 and spaced farther apart from each other near the periphery of the applicator guide 11.

[0040] Referring now to FIG. 4A, the applicator guide 11 is shown with a catheter 12 loaded into each of the through-holes 31 of the applicator guide 11. The combination of the applicator guide 11 and catheter 12 is referred to herein as the applicator assembly. In this embodiment, a triangular imprint is visible in the catheter. This shape may be the result of the applicator guide 11 and catheter 12 being positioned over a patient's nose as shown in FIG. 1B. Each catheter 12 is free to move independently along its respective through-hole 31 channel, allowing each catheter to conform to the surface it comes into contact with. When the applicator guide is oriented as depicted in FIG. 1B, the catheters are free to move along the through-hole channels and ultimately conform to the patient's nose, resulting in the triangular imprint 33 shown in FIG. 4A. Although a triangular shape is depicted in FIG. 4A, the applicator guide 11 may conform to any other shape.

[0041] Referring now to FIG. 4B, the applicator guide 11 is depicted. Unlike FIG. 4A, only some of the through-holes 31 may be occupied by catheters 12 connected to an afterloader 14 and designed to receive a radiation source. Other through-holes in FIG. 4B may be occupied by shielding inserts 34, similar in shape to the catheters 12 but designed to move freely within the through-hole 31 channels. The catheters 12 carry the radiation sources and thus deliver radiation therapy to the patient. The catheters 12 may be inserted into specific through-hole 31 locations throughout the applicator guide 11. The locations of the catheters 12 can be selected to deliver radiation therapy only to a localized area, or target, on the surface of the patient's skin. The shielding inserts 34 may be made of a radiation-shielding material, such as tungsten, or any other material exhibiting similar qualities. Thus, the shielding inserts 34 can surround the catheter 12, as shown in FIG. 4B, to block radiation scattering from uninvolved skin outside the skin radiation target.

[0042] Referring now to FIG. 5, a cross-sectional view of the applicator guide 11 is depicted. A catheter 12 may extend through each through-hole channel 32. As shown in FIG. 5, each catheter 12 may include a stopper 35 that may be coupled to the exterior surface of the catheter 12. The stopper 35 may be a protrusion that extends beyond the diameter of the catheter 12 and may extend 360° or only partially around the catheter 12. When the catheter 12 is coupled to the stopper 35, the stopper 35 will not fit inside the through-hole channel 32, preventing the catheter 12 from extending downward into the through-hole channel 32 beyond the stopper 35. This may be desirable to prevent the catheter 12 from slipping completely through the applicator guide 11 and / or to otherwise limit the allowable movement of the catheter 12. It may be even more desirable to include a second stop below the through-hole channel 32 to prevent the catheter 12 from exiting the applicator guide 11 from the other direction, thus further limiting the range of motion of the catheter 12.

[0043] As shown in FIG. 6A, the applicator guide 11 may include a guide extender 36. The guide extender 36 may be removably coupled to the applicator guide 11 via legs 40 to provide greater stability to the catheter 12. The guide extender 36 may have a plurality of through-holes 31 and corresponding through-hole channels 38 extending therethrough and aligned with the through-holes 31 and through-hole channels 32. FIG. 6B is an exemplary top view of the guide extender 36 having the through-holes 31. Thus, the catheter 12 and / or the shield insert 34 may be positioned through the guide extender 36 and the applicator guide 11.

[0044] The guide extender 36 can be positioned at a certain height above the applicator guide 11 via the legs 40. The distance between the guide extender 36 and the applicator guide 11 can be adjusted. In the embodiment shown in FIG. 6A , the guide extender 36 can include several screw holes 39 in the legs 40 for inserting screws 41. The applicator guide 11 can include a threaded portion (not shown) into which the screws 41 can be threaded to secure the guide extender 36 in place. In this manner, the distance between the guide extender 36 and the applicator guide 11 can be adjusted by installing the screws 41 into different screw holes 39. However, it will be understood that different adjustment structures can be used to adjust the height of the guide extender 36. For example, the guide extender 36 can be coupled to the applicator guide 11 via a rail system, with the guide extender 36 sliding up and down on a lace system and locked into place (e.g., with a screw or latch). In another embodiment, the guide structure may be permanently connected to the applicator guide 11 or formed from the same piece.

[0045] Referring now to FIG. 7 , spring assembly 45 is depicted. Spring assembly 45 includes applicator guide 11 and guide extender 36. Spring assembly 45 further includes springs 46 aligned with through-bore channels 38, each of which may have elastic properties such that it compresses to a length less than its neutral length when a compressive axial force is applied and returns to its neutral length when the force is removed. Each spring 46 may have an internal void sized to allow catheter 12 and / or shield insert 34 to move freely within spring 46. For example, spring 46 may have the same inner diameter as through-bore channels 38 and 32.

[0046] The spring 46 may be coupled to the guide extender 36 on its underside. Alternatively, the spring 46 may be sandwiched between the guide extender 36 and the lower protrusion 47. The lower protrusion 47 may extend from the catheter 12 and be sized and shaped to prevent the spring 46 from extending beyond the lower protrusion 47. As shown in FIG. 7, the lower protrusions 47 are triangular in shape, but they may be any other shape that prevents the spring 46 from extending beyond. Preferably, the lower protrusion 47 is recessed into the catheter 12 to allow the lower protrusion 47 to fit within the through-bore channel 38 of the guide extender 36.

[0047] The catheter 12 may further include an upper protrusion 48. The upper protrusion 48 may extend from the catheter 12 and be sized and shaped to prevent the catheter 12 from extending within the through-hole channel 38. As shown in FIG. 7A , the upper protrusion 46 is triangular in shape, although it is understood that the upper protrusion 48 may take any other shape that prevents the catheter 12 from traversing the through-hole channel 38. The upper protrusion 48 serves to restrain the movement of the catheter 12 and prevent the catheter 12 from extending beyond a certain point, but it is understood that the upper protrusion 48 is optional in that it is not necessary for the spring 46 to achieve their intended functionality as described herein.

[0048] The spring assembly 45 can be used to limit the range of motion of the catheter 12. The spring assembly 45 can be positioned to administer therapy to a patient in an orientation similar to that shown in FIG. 1B. As described above with respect to FIG. 1B, the catheter 12 will contact a surface of the patient (e.g., the patient's face). Thus, the catheter 12 will experience an opposing upward force upon contact with the patient's surface. The upward force will tend to move the catheter upward toward the applicator guide 11 and guide extender 36.

[0049] As catheter 12 moves upward, the lower protrusion 47 also moves upward toward guide extender 36. Since guide extender 36 remains stationary, the upward movement of lower protrusion 47 must compress spring 46. At a certain point, spring 46 cannot compress any further. Thus, spring 46 defines the range of motion of catheter 12, in that catheter 12 is allowed to travel upward a distance between the spring's neutral length and its fully compressed length. Spring assembly 45 provides improved control over catheter movement, and therefore radiation treatment distribution.

[0050] Referring now to FIG. 8 , a sensor assembly 50 is depicted. The sensor assembly 50 includes at least the applicator guide 11 and the guide extender 36. The sensor assembly 50 may further include a reference identifier 51 and a sensor 52. The sensor 52 may be located on the guide extender 36 proximate the through-hole 31. The sensor 52 may sense the position of the reference identifier 51 and determine whether the reference identifier 51 exceeds a threshold distance from the sensor 52. The sensor 52 may communicate with and / or otherwise interface with the reference identifier 51 via wired or wireless communication. For example, the sensor 52 may be a photoelectric sensor. Alternatively, the sensor 52 may be any other known wired or wireless sensor designed to determine the position of the catheter 12 and / or the reference identifier 51.

[0051] The applicator guide 11 and / or the guide extender 36 may be coupled to or otherwise contain a power source, such as a battery, to provide power to the sensor 52. The applicator guide 11 and / or the guide extender 36 may also include a transceiver in communication with the sensor 52. Alternatively, the sensors 52 may each include a transceiver. The sensors 52 may communicate with the computing device 15 via the transceiver through any well-known wireless connection (e.g., Bluetooth®, WiFi™, etc.). Alternatively, the sensors 52 may communicate with the computing device 15 via a wired connection.

[0052] The sensors 52 may determine the distance the reference identifier 51 has been displaced from the sensor 52 or some other neutral position. The sensors 52 may then communicate this information to the computing device 15. Each sensor may correspond to a particular catheter. The computing device 15 may run an afterloader application 29 that uses this information to selectively deliver radioactive material to particular catheters.

[0053] In one embodiment, the afterloader application 29 can analyze data received from the sensor 52 and determine that some catheters have moved beyond a certain threshold distance. For example, the sensor 52 may provide data suggesting that some catheters have moved a significant distance in response to contact with the patient's nose. A healthcare provider may be targeting the nose or a portion thereof and therefore instruct the afterloader 14 to deliver radioactive material only to catheters that have moved a certain distance.

[0054] Referring now to Figure 9, applicator guide 11, loaded with catheter 20, may be positioned over a desired portion of a patient's anatomy. While applicator guide 11 is depicted in Figure 9 as being positioned over the patient's face, it will be understood that applicator guide 11 could also be positioned over any other portion of the patient's anatomy, such as a leg or arm. To hold applicator guide 11 in place over the targeted anatomical area, applicator guide 11 may be secured to table mount 60, which rests on table 65.

[0055] To use table mount 60, a patient must be positioned on a table (e.g., an operating table) or other generally flat surface (e.g., a couch). Table mount 60 may include at least two mount arms 61 connected to a mount stabilizer 64 that rests on the generally flat surface. Mount stabilizer 64 generally maintains table mount 60, and thus applicator guide 11, in a stable position and may be threaded into or otherwise attached to the generally flat surface.

[0056] The mount arms can be connected and secured to a mount stabilizer 64. The mount arms 61 can extend upward from the mount stabilizer and connect to the applicator guide 11. The mount arms 61 can include arm extenders 62 movably connected to the mount arms 61. For example, as shown in FIG. 10 , each mount arm 61 can extend into a respective arm extender 62, and each arm extender 62 can include an engagement button 63 for locking the mount arm 61 in a particular position along the arm extender 62. The engagement button 63 can be a spring-loaded protrusion that extends into the mount arm 61 or otherwise locks the mount arm 61 in position. The engagement button 63 can be used to extend the mount arms 61 and thus raise or lower the applicator guide 11.

[0057] Mount arm 61 can be removably coupled to applicator guide 11 via any known coupling technique. For example, mount arm 61 may be coupled to applicator guide 11 via a threaded screw that is received by an internally threaded receiving portion of applicator guide 11. In another embodiment, applicator guide 11 may be snapped into place. Alternatively, table mount 60 may be permanently coupled to applicator guide 11. Table mount 60 secures applicator guide 11 so that catheter 12 is oriented in a generally upright position. In this orientation, catheter 12 is free to move downward and traverse through-bore channel 32.

[0058] 10 , applicator guide 11 loaded with catheter 20 may be positioned over a portion of a patient's head via head mount 70. For example, applicator guide 11 may be positioned over a portion of the patient's face. In another embodiment, applicator guide 11 may be positioned over a different portion of the patient's head, such as the ear. To hold applicator guide 11 in place over the targeted anatomical area, applicator guide 11 may be secured to head mount 70, which is secured to the patient's head.

[0059] The head mount 70 may include at least two mount arms 71, each connected to a respective head stabilizer 74 that is secured to the patient's head. The mount arms 71 may extend upward from the head stabilizers 74 and be connected to the applicator guide 11. The mount arms 71 may include arm extenders 72 movably connected to the mount arms 71. For example, as shown in FIG. 10 , each mount arm 71 extends into a respective arm extender 72, and each arm extender 72 may include an engagement button 73 for locking the mount arm 71 in a particular position along the arm extender 72. The engagement button 73 may be a spring-loaded protrusion that extends into the mount arm 71 or otherwise locks the mount arm 71 in position. The engagement button 73 may be used to raise or lower the mount arm 71, and thus the applicator guide 11.

[0060] The head stabilizer 74 may be secured to the patient's head via compressive pressure. The mount arm 71 and / or arm extender 72 may be made of an elastic material so that they are stretched from a neutral position when secured to the patient's head, resulting in a compressive force. Alternatively or additionally, the head stabilizer 74 may be secured to the patient's head via a strap, such as a Velcro strap, an elastic headband, or other known method. The head stabilizer 74 may include a padded portion for contacting the patient's head.

[0061] Mount arm 71 can be removably coupled to applicator guide 11 via any known coupling technique. For example, mount arm 71 may be adapted to couple to applicator guide 11 via a threaded screw that is received by an internal threaded receiving portion of applicator guide 11. In another embodiment, applicator guide 11 may be snapped into place. Alternatively, head mount 70 may be permanently coupled to applicator guide 11 or formed from the same piece.

[0062] The head mount 70 secures the applicator guide 11 so that the catheter is oriented in the same position relative to the patient's head. The patient's head may be strapped to the table 65 to maintain a constant orientation of the patient's head. The head mount 70 is preferably oriented on the patient so that the catheter 12 is in a generally upright position and is free to move downward across the through-bore channel 32.

[0063] Referring now to FIG. 11 , an optional thermotherapy catheter is depicted. Because combining radiation therapy with thermotherapy has been observed to improve cancer cell mortality and cure rates, it may be desirable to combine a conventional radiation therapy catheter with a thermotherapy needle. For example, a thermotherapy catheter 80 may have functionality and structure similar to catheter 12, but further include a heater 81 along at least a portion of catheter 80. As shown in FIG. 11 , heater 81 may be located on a wall 85 of distal end 82 of catheter 80 such that heat is applied to the target tissue when distal end 82 of catheter 80 is near the target tissue in a patient. Heater 81 may be electrically isolated from catheter 80.

[0064] The heater 81 may be connected via circuitry 83 to a power source (not shown) in electrical communication with the computing device 15. The computing device 15 may run the afterloader application 29 or a stand-alone application to selectively activate the heater 81 to heat the target tissue. The circuitry may be connected to an independent power source or may be adapted to use a power source integrated into the afterloader 14. A healthcare professional using the computing device 15 can select all catheters or only specific catheters for application of heat. Alternatively, the afterloader application 29 may be adapted to automatically apply power to specific catheters based on data received from sensors and / or according to programmed instructions.

[0065] 11 depicts catheter 80 with a heating coil, it is understood that heater 81 can employ any other known heating technique. For example, heater 81 can be a radio frequency (RF) electrode. Alternatively, heater 81 can be one or more fluid channels in wall 85 of catheter 80, with heated fluid being introduced into the one or more channels to apply heat to the target tissue.

[0066] The systems and methods described herein for delivering and guiding an applicator to a non-uniform surface in a manner that allows a catheter to conform to a curved surface and even accommodate a dynamic surface may be used to transdermally apply a therapy to a dynamic skin surface. Referring now to FIG. 12 , an applicator guide 90 for transdermal application of a therapy is provided. The applicator guide 90 may be configured similarly to the applicator guide 11 of FIGS. 4A and 4B , except that the through-hole channels 91 of the applicator guide 90 are sized and shaped to receive microneedles 92 therethrough and fit within the through-hole channels 91 with sufficient clearance to allow the microneedles 92 to move freely along the through-hole channels 91. Each microneedle 91 has a distal tip configured to non-invasively penetrate at least the stratum corneum (SC) of a patient's skin. Additionally, each microneedle 92 may be coupled to a delivery tube 93 that extends from the microneedle 92 to a therapy source, such as a drug reservoir or an ultrasound transducer or an RF energy source, such that the therapy is applied to the patient via the microneedle 92 and the delivery tube 93. A computing device may be operatively coupled to the therapy source for selectively administering the therapy.

[0067] The microneedles 92 are free to move within the applicator guide 90, so they will attempt to adapt to the contours and curvatures of the patient's body surface, and will even adapt to match variations in the surface. The microneedles 92 are oriented in a downward manner and will move downward due to gravity. Thus, the microneedles 92 will experience an opposing upward force when they contact the surface of the patient's skin, causing the microneedles 92 to conform to the patient's surface in a matching orientation. The microneedles 92 can also be oriented in other directions such that the application of a force to the applicator guide 90 toward the patient's skin will result in a counter force on the microneedles 92 when they contact the surface of the patient's skin.

[0068] The applicator guide 90 includes locks in one or more of the through-hole channels 91 for locking the microneedles 92 in a particular position, e.g., in a aligned orientation, within the through-hole channels 91. For example, the locks may include threads or other protrusions that extend into the through-hole channels 91 and contact the microneedles 92 to prevent movement of the microneedles 92 within the through-hole channels 91. The locks may be activated in unison or individually.

[0069] When the microneedles 92 are locked in a aligned orientation relative to the applicator guide 90, a force may be applied to the applicator guide 90 toward the patient's skin such that the microneedles 92 non-invasively penetrate the patient's skin with uniform pressure and to a relatively uniform depth, taking into account the contours and curvatures of the patient's body surface. As a result, the microneedles 92 can deliver therapy to the patient transcutaneously.

[0070] In some embodiments, the microneedles 92 and applicator guide 90 can be used to transdermally administer drug therapy to a patient. For example, the microneedles 92 can be coated with a drug such that the drug is delivered to the patient when the microneedles 92 are used to penetrate the patient's skin. Alternatively, the microneedles 92 can be embedded with a drug or even be degradable, for example, by applying heat to the microneedles 92, either actively by the system or naturally by the patient's body. Thus, when the microneedles 92 are positioned within the patient's skin, the microneedles 92 can degrade and deliver the drug transdermally. In another embodiment, the microneedles 92 can be used to non-invasively penetrate the patient's skin and then removed via the applicator guide 90, leaving behind a microincision in the patient's skin. A topical drug can then be administered into the microincision, allowing the drug to penetrate the stratum corneum barrier and reach the target area within the patient's skin.

[0071] Alternatively or additionally, the microneedle 92 may be hollow, e.g., have a lumen extending through the distal tip of the microneedle 92, the lumen being in fluid communication with the transfer tube 93. Thus, as shown in Figure 13, the transfer tube 93 may be coupled to the drug reservoir 102, e.g., via connection interface 16' and transfer tube 13', so that the drug can be delivered transdermally from the drug reservoir 102, through the transfer tube 13' and transfer tube 93, through the distal end of the microneedle 92, and into a target area within the patient's skin.

[0072] The computing device 15' may be a stand-alone computing device or may be incorporated into the drug reservoir 102. The drug reservoir 102 may include a pumping mechanism to deliver the drug from the drug reservoir 102 through the transfer tube 13'. The computing device 15' may communicate with the drug reservoir 102 via any known wired or wireless connection (such as BlueTooth®, Wi-Fi Direct™, etc.). A clinician may use the computing device 15' to adjust the drug dose and treatment time to control the drug reservoir 102 to deliver the appropriate amount of drug to the patient.

[0073] In some embodiments, the applicator guides described herein can be used to deliver energy percutaneously and / or transdermally to a target area within a patient's skin via a plurality of delivery tubes, catheters, and / or microneedles. For example, the applicator guides can be used to deliver radio frequency (RF) energy, ultrasound energy, or laser energy percutaneously and / or transdermally to a target area on / in a patient's skin.

[0074] As shown in FIG. 14 , the distal end of the delivery tube 113 may be a needle-like electrode 112 electrically coupled to a pulse generator 114. The delivery tube 113 may be coupled to the pulse generator 114 via delivery tube 13″ and connection interface 16″. The computing device 15″ may be a stand-alone computing device or may be incorporated into the pulse generator 114. The pulse generator 114 may be programmed to deliver sufficient RF energy to a target area on / in the patient's skin to ablate the target tissue. For example, the needle-like electrode 112 may be guided by an applicator guide 110 to match the contours of the target area on the patient's skin so that RF energy can be delivered uniformly to the target tissue.

[0075] Alternatively, the pulse generator 114 can be programmed to deliver RF energy (e.g., sufficient for depigmentation, such as tattoo removal) to a target area within the patient's skin. Thus, the needle-like electrode 112 can be locked into position relative to the applicator guide 110 and non-invasively penetrate the stratum corneum (SC) of the patient's skin to deliver RF energy to the target area within the patient's skin. The computing device 15'' can communicate with the pulse generator 114 via any well-known wired or wireless connection (e.g., Bluetooth®, Wi-Fi Direct™, etc.). A clinician can adjust RF energy emission and treatment time using the computing device 15'' to control the pulse generator 114 to deliver the appropriate amount of RF energy to the patient, e.g., for ablation and / or depigmentation.

[0076] As shown in FIG. 15 , the distal end of the delivery tube 123 may include a piezoelectric element 122 electrically coupled to a power generator 124. The delivery tube 123 may be coupled to the power generator 124 via the delivery tube 13′″ and the connection interface 16′″. The computing device 15′″ may be a standalone computing device or may be incorporated into the power generator 124. The power generator 124 may be programmed to vibrate the piezoelectric element 122 and emit sufficient ultrasonic energy to ablate the target tissue at a target area on / in the patient's skin. For example, the piezoelectric element 122 may be guided by the applicator guide 120 to conform to the contours of the target area of the patient's skin so that the ultrasonic energy may be uniformly delivered to the target tissue. In some embodiments, the piezoelectric element 122 may be locked into position relative to the applicator guide 120 and non-invasively penetrate the stratum corneum (SC) of the patient's skin to deliver ultrasonic energy to the target area within the patient's skin.

[0077] Alternatively, the power generator 124 may be programmed to deliver sufficient ultrasonic energy for ultrasonic imaging to a target area on / in a patient's skin, such that one or more piezoelectric elements 122 function as an ultrasonic imaging probe. The computing device 15''' may communicate with the power generator 124 via any well-known wired or wireless connection (e.g., Bluetooth®, Wi-Fi Direct™, etc.). A clinician may use the computing device 15''' to adjust ultrasonic energy emission and treatment time to control the power generator 124 to deliver the appropriate amount of ultrasonic energy to the patient, e.g., for ablation and / or imaging.

[0078] As shown in FIG. 16 , the distal end of the delivery tube 133 may have a laser emitter 132 operatively coupled to an energy source 134. The delivery tube 133 may be coupled to the energy source 134 via delivery tube 13″″ and connection interface 16″″. The computing device 15″″ may be a stand-alone computing device or may be incorporated into the energy source 134. The energy source 134 may be programmed to cause the laser emitter 132 to emit sufficient laser energy to ablate the target tissue at a target area on / in the patient's skin. For example, the laser emitter 132 may be guided by the applicator guide 120 to match the contours of the target area of the patient's skin so that the laser energy can be delivered uniformly to the target tissue.

[0079] Alternatively, the energy source 134 can be programmed to deliver laser energy (e.g., sufficient for depigmentation, such as tattoo removal) to a target area within the patient's skin. Thus, the laser emitter 132 can be locked into position relative to the applicator guide 130 and non-invasively penetrate the stratum corneum (SC) of the patient's skin to deliver laser energy to the target area within the patient's skin.

[0080] While various illustrative embodiments of the invention have been described above, it will be apparent to those skilled in the art that various changes and modifications can be made thereto without departing from the invention. It is intended that the appended claims cover all such changes and modifications that fall within the true spirit and scope of the invention. [Explanation of symbols]

[0081] 10 Radiation Therapy System 11 Applicator Guide 12 Catheter 12 13, 13', 13'', 13''', 13'''' Transfer pipe 14 Afterloader 15, 15', 15'', 15'''', 15'''' computing devices 16, 16', 16'', 16'''', 16'''' connection interface 21 Processing Unit 22 Memory 23 Communication Unit 24 Input Devices 25 Output Devices 26 Power Source 27 Storage 28 Operating Systems 29 Afterloader Applications 31 Through hole 32 through-hole channels 33 Imprint 34 Shield insert 35 Stopper 36 Guide extender 38 through-hole channels 39 screw holes 40 Legs 41 Screw 45 Spring assembly 46 Spring 47 Lower protrusion 48 Upper protrusion 50 Sensor assembly 51 Reference Identifier 52 sensors 60 Table Mount 61 Mount arm 62 Arm extender 63 Engagement button 64 Mount Stabilizer 65 tables 70 Head Mount 71 Mount arm 72 Arm extender 73 Engagement button 74 Head stabilizer 80 Hyperthermia Catheter 81 Heater 82 distal end 83 Circuit Configuration 85 Wall 90 Applicator Guide 91 through-hole channel 92 Microneedle 93 Transfer pipe 102 Drug Reservoir 110 Applicator Guide 112 Electrode 113 Transfer pipe 114 Pulse Generator 120 Applicator Guide 122 Piezoelectric element 123 Transfer pipe 124 Power Generator 130 Applicator Guide 132 Laser Emitter 133 Transfer pipe 134 Energy Sources W Applicator guide width L Applicator guide length H Applicator guide height

Claims

1. In the therapy delivery system, an applicator guide having a plurality of through-hole channels extending from a first side of the applicator guide to a second side of the applicator guide, the plurality of through-hole channels being arranged in an array; a plurality of catheters configured to administer a predetermined therapy, each catheter of the plurality of catheters disposed in a respective one of the plurality of through-hole channels in the applicator guide, the catheters being independently and freely movable within the respective through-hole channel with at least one degree of freedom, whereby the catheters are configured to conform to the contours of an area of skin of a patient and to contact the area in a conforming orientation; The system, wherein the plurality of catheters are configured to administer a predetermined therapy to at least a portion of the area of the patient's skin while the plurality of catheters are positioned in the aligned orientation.

2. 10. The system of claim 1, wherein the plurality of catheters comprise a plurality of microneedles configured to non-invasively penetrate a stratum corneum (SC) of the patient's skin, such that the plurality of microneedles are configured to selectively administer a predetermined therapy percutaneously to the at least a portion of the area.

3. 3. The system of claim 2, wherein the applicator guide includes a plurality of locks, each of the plurality of locks operatively coupled to a respective one of the plurality of microneedles to lock the respective one of the plurality of microneedles in the aligned orientation, such that the plurality of microneedles are configured to non-invasively penetrate the stratum corneum (SC) of the patient's skin in the aligned orientation.

4. The system of claim 3 , wherein the locks are configured to be activated individually or simultaneously.

5. 3. The system of claim 2, wherein the plurality of microneedles are configured to selectively deliver a drug transdermally to the at least a portion of the area.

6. The system of claim 5 , wherein the plurality of microneedles are coated with the drug.

7. 6. The system of claim 5, wherein the plurality of microneedles comprises an internal lumen such that the drug is configured to be delivered transdermally through the internal lumens of the plurality of microneedles to the at least a portion of the area.

8. 6. The system of claim 5, wherein the drug is embedded within the plurality of microneedles, and at least a portion of the plurality of microneedles are configured to degrade to deliver the drug transdermally to the at least a portion of the area.

9. The system of claim 1 , wherein the plurality of catheters are operatively coupled to a pulse generator and configured to selectively deliver RF energy to the at least a portion of the area.

10. The system of claim 1 , wherein the plurality of catheters are operatively coupled to ultrasound transducers and configured to selectively deliver ultrasound energy to the at least a portion of the area.

11. The system of claim 1 , wherein the plurality of catheters are operatively coupled to an afterloader and configured to selectively administer radiation therapy to the at least a portion of the area.

12. The system of claim 11 , wherein each of the plurality of catheters is configured to be individually activated to deliver radiation.

13. 12. The system of claim 11, wherein the afterloader is connected to each of the plurality of catheters via a plurality of transfer tubes, the system further comprising a computing device in communication with the afterloader and configured to command the afterloader to deliver radioactive material to the plurality of catheters.

14. The system of claim 1 , wherein one or more of the plurality of catheters are configured to simultaneously apply heat to the target area while administering a predetermined therapy.

15. 1. A method for administering a predetermined therapy to a patient, comprising: positioning an applicator guide over a target area of the patient, the applicator guide comprising a plurality of through-hole channels; loading a plurality of catheters into the through-hole channels of the plurality of through-hole channels, such that each of the plurality of through-hole channels is loaded with a catheter of the plurality of catheters; aligning the plurality of catheters with the target area of the patient, the plurality of catheters being independently and freely movable in at least one degree of freedom within the through-hole channels, whereby the plurality of catheters are configured to align with the contour of the target area of the patient in an aligned orientation; administering a predetermined therapy to the target area of the patient via at least one of the plurality of catheters in the aligned orientation.

16. 16. The method of claim 15, wherein the plurality of catheters comprises a plurality of microneedles, the method further comprising locking the microneedles in the aligned orientation.

17. 17. The method of claim 16, further comprising penetrating a stratum corneum (SC) of the patient's skin with the plurality of microneedles in the aligned orientation, and administering a predetermined therapy to the target area of the patient comprises administering a predetermined therapy to the target area of the patient transcutaneously.

18. 20. The method of claim 17, wherein transcutaneously administering a predetermined therapy to the target area of the patient comprises delivering a drug to the target area of the patient.

19. 20. The method of claim 17, wherein transcutaneously administering a predetermined therapy to the target area of the patient comprises delivering energy to the target area of the patient.

20. 16. The method of claim 15, wherein administering a predetermined therapy to the target area of the patient comprises delivering a radioactive material to at least one of the plurality of catheters.

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