Methods and systems for controlling the delivery of energy to a filament device

Abstract

Systems and methods for controlling the delivery of energy for thermal ablation. The apparatus may include: a conductive member comprising an array of conductive filaments; a power source configured to supply current to the conductive / resistive member in multiple electrical pulses; and processing circuitry coupled to the power source. The processing circuitry is configured to control the power source current value to be greater than or equal to a first current density and less than or equal to a second current density, and to control the pulse length to be greater than or equal to the first pulse length and less than the second pulse length, and to control the power source current value to have a third current density at a first time and a fourth current density at a second time.

Description

Technical Field

[0001] This disclosure relates to thermal tissue ablation or flash evaporation using metal filaments as conduits for energy delivery and / or transfer to the tissue to be ablated. More specifically, this disclosure relates to converting electrical energy into heat for ablation of tissue.

[0002] background

[0003] During skin piercing, the skin can be ablated using a metal filament that reaches high temperatures by providing electrical energy through it and transferring the resulting heat energy (heat) from the skin surface into the skin. The rapid introduction of heat energy into the skin causes a rapid rise in temperature of one or more outer layers of the skin, resulting in the ablation of at least a portion of the skin. Instantaneous (or near-instantaneous) ablation ensures the removal of the stratum corneum (the outermost protective layer of the skin, which prevents foreign substances from entering the body protected by the skin and prevents the loss of bodily fluids) from the skin. The removal of the stratum corneum creates an opening (sometimes called a "pore") the depth of which is proportional to the electrical energy provided through the metal filament.

[0004] The epidermis is a layer of skin that is aqueous and serves as a conduit for formulated active pharmaceutical ingredients. If the electrical energy supplied through the metal filament is sufficiently large and delivered rapidly enough, the resulting heat ablates the stratum corneum and exposes at least a portion of the epidermis. Providing more energy to the skin will cause more epidermal (e.g., water) to evaporate and create deeper pores. While deeper and more numerous pores do not always result in higher flux rates (e.g., some formulations may be affected by molecules present in the interstitial fluid, making too many pores impair flux rates), in many cases, deeper pores can promote (or provide) a higher flux rate for the formulated active pharmaceutical ingredient, thereby providing a sufficiently desirable supply or concentration of the formulated active pharmaceutical ingredient via the skin. Summary of the Invention

[0005] The methods, apparatuses, or devices disclosed herein each have several aspects, none of which is solely responsible for their desired properties. Without limiting the scope of this disclosure (e.g., as expressed by the appended claims), its more prominent features will now be briefly discussed. After considering this discussion, and particularly after reading the section entitled "Detailed Description," it should be understood how the described features provide advantages including data authentication services.

[0006] One embodiment includes a device for delivering thermal energy to a biofilm to cause ablation of portions of the membrane to a depth sufficient to create micropores. The device may include, for example, a perforator comprising an array of conductive filaments, wherein the perforator is configured to generate thermal energy based on an electric current flowing through the array of conductive filaments and to provide the thermal energy to the biofilm adjacent to the perforator. The device may also include a power supply circuit configured to supply current to the perforator in multiple pulses. Various embodiments of such a device may include one or more other features, including one or more features described below.

[0007] In some embodiments of a device for delivering heat energy to a biofilm to cause ablation of portions of the membrane to a depth sufficient to create micropores, the power supply circuitry includes control circuitry coupled to a power source, the control circuitry being configured to control one or more parameters of a plurality of pulses. In some embodiments, the control circuitry controls one or more parameters to achieve a perforator heating process. In some embodiments, the control circuitry controls one or more parameters to achieve a perforator cooling process. In some embodiments, the control circuitry controls one or more parameters to achieve a perforator thermal maintenance process. In some embodiments, the one or more parameters include a current value representing the current amplitude of at least one pulse.

[0008] In some embodiments of an apparatus for delivering thermal energy to a biofilm to cause ablation of portions of the membrane to a depth sufficient to create micropores, one or more parameters include frequency values ​​representing the frequency of at least a portion of a plurality of pulses. In some embodiments, one or more parameters include pulse width values ​​representing the pulse width of at least one of the plurality of pulses. In some embodiments, a control circuit controls the current values ​​of the plurality of pulses such that the control current value is greater than or equal to a first current density and less than or equal to a second current density, the second current density being greater than the first current density. In some embodiments, the control circuit controls the current values ​​to have a third current density at a first time and a fourth current density at a second time, the third and fourth current densities being between or equal to the first and second current densities, the fourth current density being less than the third current density, and the second time being later than the first time. In some embodiments, the control circuit controls the pulse length of the plurality of pulses to be greater than or equal to the first pulse length and less than the second pulse length, the second pulse length being greater than the first pulse length. In some embodiments, the control circuit is also configured to control the power supply current value to flash a portion of the membrane while minimizing the possibility of filament failure and melting.

[0009] Any of the embodiments discussed above may include one or more features, or other features, described herein. In some embodiments, the control circuitry may also be configured to determine the supply ratio of current to the cross-sectional area of ​​the conductive filament array, and control the supply ratio between a first threshold and a second threshold greater than the first threshold. In some embodiments, the control circuitry is also configured to combine and control the pulse length of multiple pulses and the pulse period between consecutive pulses to flash the skin surface while minimizing the possibility of filament failure and melting. In some embodiments, the power supply circuitry is also configured to monitor and control the temperature of the conductive filament array to prevent filament failure and melting or failure into an open circuit state. In some embodiments, the power supply is also configured to monitor the temperature of the conductive filament array at least in part based on the resistance of the conductive filament array. In some embodiments, the power supply circuitry is also configured to monitor the temperature of the conductive filament array at least in part based on received sensed temperature information. In some embodiments, the device further includes at least one sensor configured to provide temperature information to the power supply circuitry. In some embodiments, the power supply circuitry is also configured to determine whether the pressure applied to the skin surface by the conductive member is greater than or equal to a first pressure threshold. In some implementations, the second pulse length corresponds to the maximum pulse length, and when the pulse length is less than the maximum pulse length, the user of the device experiences painless micro-perforation.

[0010] Another innovation lies in a method for delivering thermal energy to a biofilm to cause ablation of portions of the membrane to a depth sufficient to create micropores. The method may include applying a device having any of the aforementioned features to the membrane and controlling electrical pulses supplied to an array of conductive filaments to heat the array of conductive filaments, thereby causing ablation of portions of the membrane to a depth sufficient to create at least one micropore. Brief description of the attached diagram

[0012] The accompanying drawings and related descriptions are provided to illustrate specific embodiments of the invention and are not intended to be limiting.

[0013] Figure 1A This is a diagram illustrating an example of a thermal ablation system according to some implementation schemes.

[0014] Figure 1B This illustrates some implementation schemes. Figure 1A Functional block diagram of an example control unit for a thermal ablation system.

[0015] Figure 2A It is shown that, according to some implementation schemes, it may be possible Figure 1A A perspective view of an example of a filament array as part of a thermal ablation system.

[0016] Figure 2BThis is a perspective view showing an example of a filament array according to some embodiments, which shows the cross-sectional area and the direction of current flow.

[0017] Figure 3A This illustrates a thermal ablation system (e.g., Figure 1A The diagram shows a top view of a filament array of a thermal ablation system. According to some embodiments, the filament array comprises multiple filaments.

[0018] Figure 3B This illustrates an array of filaments according to some embodiments (e.g., Figure 3A An electrical schematic diagram of a portion of the filament array shown.

[0019] Figure 3C It is a top view illustrating an array of filaments with one or more filament failures.

[0020] Figure 4 This is a graph showing the temperature (Kelvin) on the y-axis as a function of time (seconds) on the x-axis under two current densities applied to the filament array.

[0021] Figure 5 This illustrates an exemplary implementation. Figure 1A The performance results of the pore generation of the filament array (measured by water loss through the epidermis) are presented in a table relative to the current density and pulse length of the energy delivered to the filament array.

[0022] Figure 6 This is a graph showing transepidermal water loss (TEWL) (y-axis) as a function of the energy (x-axis) of each filament in the filament array.

[0023] Figure 7 The diagram shows the pulse distribution, which illustrates the relationship between TEWL (y-axis) and the energy (x-axis) supplied to the filament array of the embodiment via pulses.

[0024] Figure 8 This is a graph showing the filament temperature (y-axis) of a filament array according to some embodiments, the filament temperature being generated by supplying energy to the filament array in the form of multiple pulses.

[0025] Figure 9 This is a graph showing the current and voltage signals of the energy supplied to the filament array by control according to some embodiments, as a function of time, relative to different operating stages of the filament array.

[0026] Figure 10 It is a graph showing the operating temperature distribution of the filament array as a function of time (x-axis) according to some implementation schemes.

[0027] Figure 11A and Figure 11B This illustrates an exemplary implementation. Figure 1B The figure shows the temperature curves of two different energy delivery curves of the filament array. Detailed Implementation

[0028] Although certain embodiments and examples are disclosed below, the subject matter of this invention extends beyond the specifically disclosed embodiments to other alternative embodiments and / or uses, as well as modifications and equivalents thereof. Therefore, the scope of this application is not limited to any specific embodiment described below. For example, in any method or process disclosed herein, the actions or operations of said method or process may be performed in any suitable order and are not necessarily limited to any specifically disclosed order. Various operations may be described sequentially as a plurality of discrete operations in a manner that may aid in understanding certain embodiments; however, the order described should not be construed as implying that these operations are sequentially related. Furthermore, the structures, systems, and / or apparatuses described herein may be implemented as integrated components or separate components. For the purpose of comparing various embodiments, certain aspects and advantages of these embodiments are described. It is not necessary for any specific embodiment to achieve all of these aspects or advantages. Thus, for example, various embodiments may be implemented in a manner that achieves or optimizes one or a set of advantages as taught herein, without necessarily achieving other aspects or advantages as may also be taught or implied herein.

[0029] In the following detailed description, reference is made to the accompanying drawings, which form part of this disclosure. Exemplary embodiments described in the detailed description, drawings, and claims are not intended to be limiting. Other embodiments and variations may be employed without departing from the spirit or scope of the subject matter presented herein. It will be readily understood that aspects of this disclosure as illustrated in the general description and drawings herein can be arranged, substituted, combined, and designed in a variety of different configurations, all of which are expressly contemplated and constitute part of this disclosure.

[0030] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of this disclosure. It should be understood that if a particular number of claim elements are intended, such intention will be expressly stated in the claims, and without such statement, such intention does not exist. For example, as used herein, the singular forms “a,” “an,” and “the” are intended to also include the plural forms unless the context clearly indicates otherwise. As used herein, the term “and / or” includes any and all combinations of one or more of the items listed herein. It should also be understood that the terms “comprises,” “comprising,” “includes,” and “including”, when used in this specification, specify the presence of a defined feature, integer, step, operation, element, and / or component, but do not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof. Expressions such as “at least one of…” modify the entire list of elements when preceding a list of elements, without modifying any individual element within that list.

[0031] Figure 1A An exemplary thermal ablation system 100 (sometimes referred to herein as an “applicator”) according to some embodiments is shown. In various embodiments, the thermal ablation system 100 may be a micro-perforation device. The illustrated thermal ablation system 100 includes a housing 125 that at least partially surrounds the various components of the thermal ablation system 100. A portion of the housing 125 may be a body portion 115 configured to be held in a user’s hand. The thermal ablation system 100 may also include a user interface. In various embodiments, the user interface may include a display 105 positioned to display information to a user of the thermal ablation system 100 (e.g., a user holding the body portion 115 of the thermal ablation system 100 in their hand). The thermal ablation system 100 may also include one or more controllers 110. In various embodiments, the user interface may also include one or more controllers 110. In this embodiment, one or more controllers 110 may be accessible by the hand of a user holding the body portion 115 of the thermal ablation system 100. A perforator 120 is located at one end of the thermal ablation system 100. Various implementations of the perforator 120 can be used in the thermal ablation system 100. Figure 1A The exemplary perforator 120 illustrated includes a filament array 104 comprising one or more filaments 200 operable to deliver thermal energy by direct contact with a biofilm, thereby causing ablation of portions of the membrane to a depth sufficient to form micropores.

[0032] Figure 1BThis is functional block diagram 102, which illustrates the configuration of the applicator 100 for thermal ablation according to some embodiments, for example, Figure 1A Some components of the thermal ablation system. Functional block diagram 102 illustrates examples of components that can be configured to implement and / or control the various functions described herein. Therefore, for ease of reference, functional block diagram 102 may be referred to herein as control unit 102 of applicator 100. For example, control unit 102 may control the current supplied to perforator 120, and in particular the current supplied to filament array 104. About this document Figure 1B The description states that some item numbers refer to the above combined with... Figure 1A Described aspects. In some embodiments, the control unit 102 does not include Figure 1B Each component is shown in the diagram. In some embodiments, the control unit 102 includes components for clarity of illustration. Figure 1B Additional components not shown. Furthermore, in Figure 1B The control unit 102 shown does not include all components of the applicator. For example, the control unit 102 is configured to direct the filament array 104 of the applicator 100 ( Figure 1B (Not shown in the image) provides current.

[0033] The illustrated control unit 102 includes a processor 204 that controls the operation of the control unit 102. The processor 204 may also be referred to as a central processing unit (CPU), a hardware processor, or a microprocessor unit (MPU). The control unit also includes a memory unit 206, which may include read-only memory (ROM) and random access memory (RAM), providing instructions and / or data to the processor 204 and serving as a repository for storing instructions and / or data from the processor 204. A portion of the memory unit 206 may also include non-volatile random access memory (NVRAM). The processor 204 typically performs logical and arithmetic operations based on program instructions stored in the memory unit 206 or received instructions and / or data. The instructions in the memory unit 206 may be executable to implement the methods described herein. Furthermore, the control unit 102 may utilize the memory unit 206 to store information about other components in the thermal ablation system 100, enabling the use of certain methods described below, such as storing specific setpoints, thresholds, information for supplying power to the perforator, and / or operational characteristics of the components in the thermal ablation system 100. In some implementations, the information used to power the ablation device includes information that can be used to provide electrical pulses to the ablation device to heat the filament of the ablation device, such as one or more processes for powering the ablation device. The control unit 102 can then utilize the processor 204 associated with the storage unit 206 to analyze the stored data and determine and / or identify various settings, categories, characteristics, etc., of one or more other components in the thermal ablation system 100.

[0034] Processor 204 may include or be a component of a processing system implemented by one or more processors. One or more processors may be implemented using any combination of a general-purpose microprocessor, microcontroller, digital signal processor (DSP), field-programmable gate array (FPGA), programmable logic device (PLD), controller, state machine, gated logic, discrete hardware component, special-purpose hardware finite state machine, or any other suitable entity capable of performing computation or other operations on information.

[0035] The processing system may also include a non-transitory machine-readable medium for storing software. Software should be broadly interpreted to mean any type of instruction, whether referred to as software, firmware, middleware, microcode, hardware description language, or otherwise. Instructions may include code (e.g., in source code format, binary code format, executable code format, or any other suitable code format). When executed by one or more processors, the instructions cause the processing system to perform the various functions described herein. Processor 204 may also include a packet generator to generate packets for control operations and data communications.

[0036] Control unit 102 may include networking components, such as a transmitter 210 and a receiver 212 that allow data to be sent and received between control unit 102 and a remote location. Transmitter 210 and receiver 212 may be combined into a transceiver or network interface 214. Network interface 214 (and / or transmitter 210 and receiver 212) may communicate via communication link 216, which may include a wireless or wired communication link. In some embodiments, communication link 216 may include a link to a mobile device or other user equipment for monitoring and / or tracking the use of control unit 102 and / or thermal ablation system 100. Network interface 214 works in conjunction with processor 204 to communicate via communication link 216.

[0037] The control unit 102 is at least partially enclosed by the housing 125. The housing 125 protects the components of the control unit 102 from environmental influences and provides safe operation and easy user-friendly packaging.

[0038] The control unit 102 also includes one or more energy storage devices 218. The energy storage device 218 may include one or more batteries, capacitors, or similar energy storage components. When the control unit 102 is in an operational state (e.g., in operation in the thermal ablation system 100), the energy storage device 218 provides energy to the components of the control unit 102.

[0039] In some embodiments, control unit 102 includes one or more circuits or sensors 224 configured to monitor the operation or conditions of one or more components of control unit 102. For example, sensor 224 may detect the charging state and / or health state of energy storage device 218. Additionally and / or alternatively, sensor 224 may detect the conditions of one or more components of control unit 102 that indicate a fault in control unit 102. For example, sensor 224 may detect when one or more filaments are “burnt out” or in an open circuit state or are deteriorating and approaching an open circuit state. Alternatively or additionally, sensor 224 may detect when too much or too little voltage or current is delivered to the filaments and / or when the temperature of the filaments is above, below, or at a desired threshold. In some embodiments, sensor 224 may be configured to monitor the operation of processor 204. If sensor 224 detects an overvoltage or overtemperature condition or determines that processor 204 is unresponsive, sensor 224 may generate an output. In some embodiments, the output from sensor 224 may be communicated via transmitter 210 or network interface 214 through communication link 216. In some embodiments, the output from sensor 224 may communicate internally to other components of control unit 102, such as processor 204 or user interface 222, which will be further described below.

[0040] In some implementations, when control unit 102 is initialized and / or when thermal ablation system 100 is started, sensor 224 performs an initial check to ensure all connections are correct and all components of thermal ablation system 100 are in normal operating condition. Therefore, control unit 102 can perform an initial check of thermal ablation system 100 to determine if any faults are present. If no fault is detected in or through control unit 102, control unit 102 begins supplying current to the filament. If a fault is detected, control unit 102 can be prevented from supplying current to the filament. Therefore, sensor 224 can function as a safety circuit or be used as a safety circuit to prevent thermal ablation system 100 from operating in a faulty state.

[0041] In some embodiments, sensor 224 and / or processor 204 can monitor the temperature of the conductive component. Processor 204 can also control the temperature of the conductive component to prevent filament failure, wherein filament failure results in one or more filaments melting or failing into an open circuit state. In some embodiments, the temperature is determined based on sensor 224 identifying the resistance of the conductive component, and wherein controlling the temperature to prevent filament failure includes controlling the temperature to prevent filament failure when the conductive component comes into contact with at least one of the skin surface and air.

[0042] The control unit 102 also includes a current generator 220. The current generator 220 generates a current signal supplied to the filaments, as described herein. In some embodiments, the current signal may include one or more pulses. In some embodiments, the pulses are varied to have one or more durations (e.g., time periods), amplitudes, etc., thereby controlling the temperature of the filaments and creating pores in the skin. In some embodiments, the current signal may be periodic pulses. In some embodiments, the current signal may have a constant amplitude, while in other embodiments, the current signal may include two or more pulses of different amplitudes. In some embodiments, the current signal has a constant frequency, while in other embodiments, the current signal includes two or more groups of pulses of different frequencies. For example, the current generator 220 may generate current signals with different properties during different time periods, which are transmitted to the filament array 104 via the control unit 102. During a first time period, a current signal having a first set of properties may be generated, such as a single pulse or two or more pulses with the same or similar amplitudes, and / or a group of pulses with a specific frequency. During the second time period (e.g., a subsequent time period), a current signal with a second set of properties may be generated, such as one or more pulses having an amplitude different from that of the pulses generated during the first time period, and / or one or more pulses having a frequency different from that of the pulses generated during the first time period.

[0043] In some embodiments, processor 204 allows or interrupts the generation and transmission of a current signal to the filament based on conditions detected by sensor 224 or commands from processor 204. In some embodiments, interrupting the generation and transmission of the current signal includes terminating or reducing the current signal.

[0044] In some embodiments, the pulse can have an associated voltage of 1 to 42 VAC. For example, in various embodiments, the pulse can have an AC voltage of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, or 42 VAC. In some embodiments, the voltage can be greater than 42 VAC. In some embodiments, the pulse duration can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 milliseconds. In some embodiments, the pulse duration can be greater than 12 ms. As the pulse duration increases (e.g., when it approaches 16 ms), the patient may begin to feel heat, regardless of how low the current is. In some implementations, the pulse may have a length or period that can be adjusted based on application requirements.

[0045] In some aspects, the control unit 102 also includes a user interface 222. The user interface 222 may include a keyboard and / or a display. The user interface 222 allows a user to control the operation of the control unit 102 and / or the thermal ablation system 100. The user interface 222 may include any elements or components that communicate information to the user of the control unit 102 and / or receive input from the user.

[0046] The control unit 102 also includes an input / output (I / O) circuit assembly 228. In some embodiments, the I / O circuit 228 may include components that allow the control unit 102 to be coupled to one or more other components (e.g., filaments) in the thermal ablation system 100. In some embodiments, the I / O circuit 228 includes connectors (e.g., a Universal Serial Bus (USB) connector, a proprietary connector, or any other connector) that physically connect the control unit 102 to other components. In some embodiments, the I / O circuit 228 includes components that detect incorrect connections between the control unit 102 and / or other components.

[0047] Various components of control unit 102 can be interconnected via bus system 226. Bus system 226 may include, for example, a data bus, as well as power buses, control signal buses, and status signal buses in addition to the data bus. Those skilled in the art will understand that the various components of control unit 102 can be interconnected or receive or provide input to each other using some other mechanism.

[0048] Despite Figure 1B Several individual components are shown, but those skilled in the art will understand that one or more of these components can perform not only the functions described above, but also the functions of the other components described above. For example, processor 204 can be used not only to perform the functions described above, but also to perform the functions of current generator 220 and / or sensor 224 described above. Figure 1B Each component shown can be implemented using multiple individual elements.

[0049] In some embodiments, one or more components of control unit 102 may provide a means of locking control unit 102 to prevent abuse or improper use of thermal ablation system 100. Additionally or alternatively, one or more components of control unit 102 may count the usage or dosage provided by thermal ablation system 100 and / or provide reminders about upcoming doses. In some embodiments, network interface 214 may be used to communicate with a doctor or pharmacy to refill prepared medications or change dosages as needed. In some embodiments, user interface 222 may provide personalization of thermal ablation system 100 and offer voice prompts, guide lights, etc., to simplify operation of thermal ablation system 100.

[0050] exist Figure 1AIn the thermal ablation system 100, a current signal generated and applied to the filament array 104 by the current generator 220 of the control unit 102 heats the filament array 104 and uses it as an energy / heat delivery medium. The filament array 104 provides a sufficient amount of energy / heat to the skin to ablate at least the surface of the skin (i.e., the stratum corneum). In some embodiments, the amount of energy / heat delivered to the skin by the filament array 104 is varied by changing the current delivered to the filament array 104 or by changing the amount of time the filament array 104 delivers energy to the skin. For example, the current generator 220 can change the amount of time the filament array 104 delivers energy to the skin. In some embodiments, the amount of time can be varied by changing the amount of time the filament array 104 is in contact with the skin and / or by changing the pulse length of the current delivered to the filament array 104. For example, the current generator 220 can change the pulse length of the current signal. To perform skin ablation, the current applied to the filament array 104 can raise the temperature of the filament array 104 above the melting point of the stratum corneum and epidermis, but below the melting point of the filament array 104 itself. In some embodiments, the target temperature for ablation by the filament array 104 can be about or substantially 123°C.

[0051] Figure 2A According to the exemplary implementation scheme Figure 1A A perspective view of the filaments 200 of the filament array 104 of the thermal ablation system 100. As shown, the filaments 200 have a three-dimensional shape and have a height 201, a length 203, and a width 205. The filaments 200 are formed of or contain conductive materials (e.g., stainless steel, or other metals or similar conductive materials). In some embodiments, the filaments 200 may be microfilaments or similar filaments. For example, the filaments 200 may be 50 μm wide, 15 μm thick, and 400 μm long. Although the filaments 200 shown have a generally rectangular block or prism shape, the filaments 200 may have any other shape, such as a trapezoidal shape. The shape of the filaments may also be, but is not limited to, serpentine bands, ellipses, circular or elliptical loops with varying widths, or "X" shapes or star shapes. The shape of the cross-section 207 of the filaments may be, but is not limited to, square, rectangular, trapezoidal, elliptical, or crescent-shaped. The filament can be planar (where the X and Y dimensions are in a plane, or substantially in a plane) or three-dimensional (3D), bent at a portion of its length between two anchor points at its end.

[0052] The filament 200 can create pores in the skin by transferring sufficient energy from the filament 200 to the skin to ablate the stratum corneum, thereby exposing the epidermis. The amount of energy transferred from the filament 200 to the skin can be based on the temperature difference between the skin and the filament 200, the material of the filament 200, the properties of the skin (e.g., skin type, morphology, elasticity, hydration, and thermodynamic parameters of the skin layers), and the contact / pressure between the filament 200 and the skin. In some embodiments, a vacuum can be used to increase the contact between the filament 200 and the skin. For example, a perforator including the filament array 104 may include holes or other structures that, when connected to a vacuum cleaner, cause the skin to be “sucked” toward the holes or structures, increasing the contact between the filament 200 and the skin. In some embodiments, a portion of the filament 200 may be bent and protrude from the plane in which the filament array is typically aligned, thereby creating additional pressure points.

[0053] In some embodiments, control unit 102 may determine whether the pressure applied to the skin surface by the conductive member (e.g., filament array 104) is greater than or equal to a first pressure threshold. For example, in some embodiments, control unit 102 may receive information from at least one sensor 224 and use the received information to determine whether the pressure applied to the skin surface by the conductive member is greater than or equal to the first pressure threshold. In some embodiments, control unit 102 may use information from processor 204 to determine whether the pressure applied to the skin surface by the conductive member is greater than or equal to the first pressure threshold, for example, by comparing the sensed pressure information with one or more pressure values ​​(e.g., thresholds) stored in memory.

[0054] Figure 2B According to the exemplary implementation scheme Figure 2A A perspective view of the filament 200 shows the cross-sectional region 207 and the current flow direction 209. As shown, the cross-sectional region 207 is trapezoidal, and the current flows through the filament 200 in the current flow direction 209. The cross-sectional region 207 of the filament 200 can be of any shape (e.g., square, rectangle, circle, ellipse, triangle, other polygons, etc.). In various embodiments, the current flow can be in a direction substantially perpendicular to the cross-sectional region 207 of the filament 200. Based on the current flowing through the filament 200 and the cross-sectional region 207, the current density / flux can be determined according to the following Equation 1:

[0055] Current density = I / A

[0056] (Equation 1)

[0057] in:

[0058] • I – The current flowing through the filament 200, and

[0059] • A – The cross-sectional area of ​​the filament 200.

[0060] Based on Equation 1, as the cross-sectional area of ​​the filament 200 increases, the current must be increased accordingly to maintain the current density. As the length of the filament 200 increases, the resistance of the filament 200 can be increased accordingly, resulting in an increase in voltage and power for the filament 200 as its mass increases.

[0061] The current density of the filament 200 can be used to determine the operable range of the filament array 104 in producing feasible pores without causing pain or damage to the filament array 104, as will be described in further detail below. The depth of the pores produced in the skin is proportional to the energy delivered to the skin via the filament 200.

[0062] In some embodiments, control unit 102 (e.g., via processor 204) determines the supply ratio of the current signal to the cross-sectional area of ​​the filament 200. Control unit 102 also controls the supply ratio between a first threshold and a second threshold, where the second threshold is greater than the first threshold. In some embodiments, the first and / or second thresholds are predetermined and may be stored in memory (e.g., memory 206 of control unit 120). In some embodiments, the first and / or second thresholds are dynamic during operation, for example, using information from sensors sensing the characteristics of the filament or skin (e.g., temperature). In some embodiments, the first and / or second thresholds are downloadable and stored in the system's memory, such as memory 206 of control unit 120.

[0063] Figure 3A According to the exemplary implementation scheme Figure 1A A top view of a representative filament array 104 of a thermal ablation system 100, including multiple filaments 200 as shown in Figure 2. The filament array 104 includes multiple filaments 200 disposed between conductive support members or structures 300. Although in Figure 3A Although not shown, the conductive support member 300 can be connected to a power source. Figure 3A One embodiment of the configuration / design of the filament array 104 is shown, but such filament arrays are not limited to this configuration / design. Instead, other configurations / designs of the filament array can also be employed as discussed herein.

[0064] In some embodiments, the conductive support member 300 is made of copper or a similar conductive material. In some embodiments, the conductive support member 300 is the same material as the filament 200. In some embodiments, the conductive support member 300 is a different material from the filament 200. Figure 3BAs shown, the conductive support member 300a includes fingers or similar protrusions 301, with filaments 200a to 200k disposed between the fingers or similar protrusions 301, where 1 < k. Although not shown, a corresponding conductive support member 300b may have fingers 301 intersecting with the fingers 301 of the conductive support member 300a.

[0065] The conductive support member 300 provides structural support for the filament 200 by holding it in proper position between the fingers of the conductive support member 300. Additionally and / or alternatively, the conductive support member 300 electrically connects the filament 200 to a power source.

[0066] Figure 3B This illustrates an exemplary implementation. Figure 3A A schematic diagram of an example of a filament array 104. Figure 3B A conductive support member 300a is shown, having a row (row 1) of filaments 200 disposed between conductive support members 300a and 300b. In the case of n rows of filaments 200, there are m conductive support members 300 to support the n rows of filaments 200, where 1 ≤ n ≤ m. As shown, conductive support members 300a to 300m provide a conductive connection between each of the n rows of filaments 200 and a power source, indicated by "+" and "-" symbols on conductive support members 300a and 300m, respectively.

[0067] In some implementations, using one or more components of the thermal ablation system 100 to control or alter the amount of time during which the filament 200 delivers energy (e.g., heat) to the skin can be simpler and more efficient than controlling the amount of current (e.g., amplitude) delivered through the filament 200. For example, such control of the amount of time can utilize fewer components than a system that controls or alters the amount of current delivered to the filament 200. However, when controlling or altering the amount of time during which the filament 200 delivers energy to the skin, the control unit 102 can prevent a slow rise in skin temperature, which could lead to damage (e.g., burns or dryness) to the top layer of skin (e.g., the stratum corneum and / or epidermis). Damage to the top layer of skin can create a charred / dried layer of dead tissue. This layer of dead tissue can impede the distribution of heat from the filament 200 into deeper layers of skin (e.g., the epidermis) and prevent the formation of viable pores for delivery of formulated active pharmaceutical ingredients. Additionally, damage to the skin can trigger nerve responses in the skin, thereby causing or being interpreted as pain. Therefore, the duration for which energy is supplied to the filament (e.g., in an electrical pulse) or the duration for which the filament 200 is in contact with the skin is preferably less than the time that would cause such damage to the skin.

[0068] Furthermore, providing a higher current through the filament allows it to reach the target temperature in a shorter time compared to providing a relatively low current. In addition, the higher current reduces the time required to produce the desired aperture size, thereby reducing or eliminating the risk of neural reactions to the heat of the filament and reducing or eliminating pain associated with ablation.

[0069] When the current generator 220 and control unit 102 supply a large current to the filament array 104 of the perforator 120, the individual filaments 200 in the filament array 104 experience a rapid increase in temperature. This temperature increase of the filaments 200 (and correspondingly, the filament array) can shorten the time required to produce the target aperture size. Therefore, the risk of developing a nerve response to heat due to heating and / or drying is reduced or eliminated, and pain associated with ablation can be reduced or eliminated.

[0070] As described above, the filament 200 transfers energy / heat from a power source to a surface, such as a patient's skin. Each filament 200 has one or more properties that may affect energy / heat transfer to the skin. For example, the filament 200 has a resistance that depends on the material used for the filament and the mechanical shape of the filament. The amount of energy supplied to and from the filament is based on the current applied to the filament 200 (i.e., based on the current generated by the current generator 220), the resistance of the filament 200, and the size of the filament. The energy supplied to the filament can be calculated using the following equations 2 and 3:

[0071] E=P t=I U t=I 2 R f t=U 2 / R f t

[0072] (Equation 2)

[0073] R f = l / (w h)

[0074] (Equation 3)

[0075] in:

[0076] E – Energy

[0077] P – Power

[0078] ·t – time

[0079] • I – A current of 200 ohms flows through the filament.

[0080] U – The voltage at the end of the filament 200.

[0081] ·R f - The resistance of a 200Ω filament

[0082] · – The specific material resistivity of the filament 200,

[0083] • l – The length of the filament is 200.

[0084] ·w – the width of the filament is 200, and

[0085] •h – Height (thickness) of the filament 200.

[0086] The amount of energy supplied to and from the filament array 104 is based on the current applied to the filament array 104 (i.e., based on the current generated by the current generator 220) and the total resistance of the filament array 104. The total resistance of the filament array 104 is determined by averaging the filaments 200 of the filament array 104. The energy supplied to and from the filament array 104 can be calculated using the following equations 4 and 5:

[0087] E=P t=I U t=I 2 R a t=U 2 / R a t

[0088] (Equation 4)

[0089] R a = R f / N fb N b )

[0090] (Equation 5)

[0091] in:

[0092] E – Energy

[0093] P – Power

[0094] ·t – time

[0095] • I – Current flowing through the filament array 104

[0096] U – The voltage on the 104-wire array contacts, and

[0097] ·R a – Average resistance of filament array 104 (depending on row configuration and array configuration).

[0098] Figure 3C According to the exemplary implementation, one or more filaments fail as 302 and 304. Figure 3A A top view of the filament array 104. A filament failure occurs when one or more of the filaments 200 in the filament array 104 are damaged and / or destroyed, such that the damaged or destroyed filament 200 cannot conduct the current generated by the current generator 220 to the skin. For example, if one of the filaments 200 is cut, broken, or melted, causing the filament 200 to no longer connect the two fingers 301 of the conductive support member 300, then the filament 200 is broken, burned, or otherwise fails. Therefore, when in a failed state, the filament 200 effectively acts as an open circuit between the fingers 301 of the conductive support member 300. Filament failures 302 and 304 correspond to individual failed filaments 200 that no longer provide a conductive path between the respective fingers 301 of the conductive support member 300 to which the failed filament 200 is connected.

[0099] In some implementations, the failure of one filament 200 in a filament array between two fingers 301 can lead to cascading filament failure. For example, when the first filament 200a in filament array 1 fails, the remaining filaments 200 in filament array 1 experience an increase in power flow due to the loss of a path through the failed filament 200a. This increased power flow through the remaining filaments 200 in filament array 1 also increases the risk of failure of one or more of the remaining filaments 200. While the failure of only filament 200a may not trigger a cascading (avalanche) effect in the remaining filaments 200 of filament array 1, cascading filament failure may occur if a sufficient number of filaments 200 in array 1 fail (e.g., about 5% of the filaments 200 in array 1). Therefore, eventually all the filaments 200 in array 1 will fail, resulting in either a complete cascading failure or an open-circuit failure. The amount of time elapsed between initial filament failure and the occurrence of complete cascade failure depends on the amount of current / energy supplied to filament 200 without being dissipated in one of the three ways described below.

[0100] In some implementations, the filament 200 is cooled, thereby dissipating the energy supplied to the filament 200. Three ways this dissipation occurs include: (1) radiating heat into the air, (2) conducting heat into the filament array 104 (e.g., a copper structure), and (3) conducting heat into the skin. Radiating heat from the filament 200 into the air is a relatively small amount of heat loss compared to heat conduction into the filament array 104 or into the skin. Therefore, radiative heat loss can generally be ignored.

[0101] Since the conductive support structure 300 is essentially a metal with high thermal conductivity, the amount of heat conducted (back) into the conductive support structure 300 is relatively large. The amount of heat loss conducted into the conductive support structure 300 can be quantified using physical laws of heat and known material properties, and will not be described in detail herein.

[0102] As described above, heat conduction to the skin depends on various skin properties, including skin type, morphology, elasticity, hydration, and thermodynamic parameters of the skin layers, as well as at least one or more of the contact / pressure between the filament array 104 and the skin. Relevant skin properties can change during perforation because different skin layers can have different properties or characteristics that affect heat conduction. For example, when the dry stratum corneum (which has a layered structure with varying consistency and thickness between different skin entities) is ablated with the filament array 104, the epidermis is exposed, which is typically more hydrated and has different properties than the dry stratum corneum.

[0103] As previously stated, the resistance of the filament 200 (and the temperature thereby reached) is proportional to the size and / or shape of the filament 200 and the energy delivered to the filament 200 (i.e., the current generated by the current generator 220). To accommodate various sizes, shapes, and energies, the relationship can be normalized using the current density defined by Equation 1 above. Based on the current density defined by Equation 1, the operational constraints leading to filament 200 failure, and the operational constraints leading to keratin ablation, a desired range of current densities is defined. The defined range of current densities identifies those that, if delivered to the filament 200, would produce feasible pores without causing pain or damaging the filament array.

[0104] Figure 4 This illustrates the application of an exemplary embodiment to Figure 1A Figure 400 shows the current density of the filament 200. Figure 400 includes temperature (in Kelvin, K, along the y-axis) as a function of time (in seconds, s, along the x-axis). Figure 400 shows three lines. Line A (1.3 mA / μm) 2 The symbol represents the minimum operational constraint required to induce keratinocyte ablation. Therefore, below 1.3 mA / µm... 2The current density will not generate the temperature required to cause keratin ablation. Line B (3.56 mA / μm) 2 This indicates an operational constraint that causes filament 200 failure or pain when the filament array 104 with this current density is applied to the skin. Therefore, above 3.56 mA / µm 2 An excessively high current density generates uncontrolled filament temperatures, leading to filament failure, complete cascade failure, and / or pain. Line 402 between line A and line B represents an exemplary current density sufficient to produce stratum corneum ablation without causing filament failure or pain. Therefore, the region between line A and line B represents a current density that will produce ablation without damaging or destroying the filament array 104 or causing skin pain or injury.

[0105] In some embodiments, the control unit 102 of the thermal ablation system 100 is configured to control (e.g., via processor 204) the current generator 220 to generate a current signal such that the current density at the filament 200 is greater than or equal to a first current density (e.g., the current density represented by line A). Alternatively, a current signal can be generated such that the current density at the filament 200 is less than or equal to a second current density (e.g., the current density represented by line B). As mentioned above, the current density of line B is greater than the current density of line A.

[0106] Figure 5 This illustrates an exemplary implementation. Figure 1A Table 500 shows the hole generation performance results of the filament array 104 relative to the current density and the pulse length of the energy delivered to the filament array 104. The columns of Table 500 show various pulse lengths (in milliseconds) representing the pulse length of the generated current signal supplied to the filament array 104. The rows of Table 500 show various current densities (mA / µm) representing the average current density of the filaments 200 in the filament array 104. 2 Table 500 shows the specific performance results produced by specific combinations of current density and pulse length.

[0107] The performance results described in Table 500 indicate that the combination of pulse length and current density results in the thermodynamic stability of the filament array 104 while simultaneously creating pores through the stratum corneum to the epidermis. Thermodynamic stability is quantified by a consistent temperature on the filament array 104 and optimized switching (<2 switches / 500 μs). Optimized switching refers to the process by which the control unit (CPU) 204 modulates the current delivered to the filament array 104. For example, switching the current supplied to the filament array on and off in a series of pulses. This switching is performed to maintain a relatively constant temperature of the filaments and to prevent the temperature from reaching the melting / burn-out / failure point, while heating the filament array sufficiently to achieve the desired effect. This can be done by using (e.g., setting) appropriate pulse parameters and comparing them with readings from sensor 224. The performance results depicted in Table 500 also show which combination of pulse length and current density requires energy regulation / compensation of the filament array 104 while simultaneously creating pores through the stratum corneum to the epidermis. For the performance results in Table 500, the filaments 200 in the filament array 104 are 50 μm wide, 15 μm thick and 400 μm long and are made of stainless steel.

[0108] As shown in Table 500, the pulse length ranges from 0.5 ms to 16 ms and the pulse density is 0.81 mA / µm. 2 The combination of current densities is safe in air without requiring additional temperature regulation. Similarly, pulse lengths of 0.5 ms to 10 ms and 1.33 mA / µm... 2 The combination of current densities is safe in air without requiring additional temperature regulation. However, as discussed above, below 1.5 mA / µm 2 The current density may be insufficient to create pores penetrating the stratum corneum to the epidermis. At current densities below 1.5 mA / μm... 2 At this time, heat from the filament 200 is absorbed and dissipated into the skin more quickly than when ablation occurs. Therefore, these combinations of pulse length and current density may not be sufficient to produce the desired pores.

[0109] Even in air, where thermal conductivity is very low, pulse lengths of 0.5 ms to 2 ms and 2.00 mA / µm are achieved. 2 The combination of current densities also creates pores penetrating the stratum corneum to the epidermis without requiring additional temperature regulation (the temperature regulation of the skin or filament array 104). Similarly, pulse lengths of 0.5 ms to 1 ms and 2.67 mA / µm 2 The combination of current densities creates pores that penetrate the stratum corneum to the epidermis without requiring additional temperature regulation (temperature regulation of the skin or filament array 104).

[0110] Pulse length of 12 ms to 16 ms and 1.33 mA / μm2 The combination of current density, a pulse length of 4 ms, and 2.00 mA / μm 2 The combination of current densities in air requires some form of temperature control or compensation (i.e., temperature regulation), but produces pores on animal skin without any additional temperature regulation.

[0111] At 3.23 mA / µm 2 At current densities, combinations of pulse lengths from 0.5 ms to 8 ms create pores in the stratum corneum of animal skin, but require additional temperature regulation and fail in air. At 2.93 mA / µm... 2 Combinations of pulse lengths from 0.5 ms to 16 ms at current densities induce pores in the stratum corneum of animal skin, but require additional temperature regulation and fail in air. At 2.67 mA / µm... 2 At current densities of 2 ms to 16 ms, pulse lengths created pores in the stratum corneum of animal skin and required additional temperature regulation, but failed in air. At 2.00 mA / µm... 2 At current densities of 3.23 mA / µm, pulse lengths of 6 ms to 16 ms ablate the stratum corneum on animal skin and require additional temperature regulation, and fail in air. 2 Combinations of pulse lengths from 10 ms to 16 ms at the given current density failed to regulate temperature on animal skin and in air.

[0112] Figure 6 This is a graph showing the transdermal water loss (TEWL) as a function of the energy of each filament in the filament array according to an exemplary embodiment.

[0113] Figure 7 This is a graph illustrating the pulse distribution according to an exemplary embodiment, showing transepidermal water loss (TEWL) (y-axis) and the pulse delivery to... Figure 1A The relationship between the energy (x-axis) of the filament array. TEWL is related to drug delivery (API diffusion into the skin). Figure 7 It is shown that for lower energies, long, uninterrupted pulses are preferable to pulses with high current densities, which would require modulation by a control unit (e.g., a CPU) to prevent the filament from burning out. For higher energy delivery, a specific (e.g., optimal) current density, or a current density slightly higher or lower than the determined optimal current density, can be used.

[0114] Figure 8 This illustrates an exemplary implementation. Figure 1AFigure 800 illustrates the filament temperature control of the filament array 104, which relates to the control of energy pulses delivered to the filament array 104. Figure 800 shows the filament temperature along the y-axis as a function of time along the x-axis. Figure 800 also shows the current amplitude along the y-axis as a function of time along the x-axis. The filament temperatures of three filament arrays (lines 807, 808, and 809) with different average widths are shown relative to a constant amplitude current signal applied to the filament array 104 (line 801). Figure 800 also includes a maximum temperature 810 of the filament 200 (e.g., the temperature at or above which the filament 200 will fail).

[0115] As described herein, the filament array 104 can receive the generated current signal (represented by line 801) from the control unit 102. The generated current signal can be received as a series of pulses or a pulse sequence. In some embodiments, during a first period 802, a current signal with a constant amplitude is received, as shown by the straight portion of line 801 during period 802. During period 802, the current signal may not be “pulsed” but rather continuously “on”. Furthermore, during period 802, in response to the “on” current signal, the filament temperature, represented by lines 807, 808, and 809, rises relatively uniformly. As mentioned above, this may be due to the current signal passing through the filament 200 and based on the resistance or resistivity of the material of the filament 200. In some embodiments, the slope or rate of temperature rise shown depends on the material of the filament 200 in the filament array 104. As shown, the temperature of the filaments 200 of the filament array 104 rises as long as a current signal is applied to the filament array 104. As shown, the filament 200, whose temperature is represented by lines 807, 808, and 809, can contain different materials, which, considering the constant current signal, results in different temperature values ​​represented by lines 807, 808, and 809. The same applies if the size of the filament varies, resulting in different resistances and heating rates.

[0116] In some embodiments, a cycle 802 in which the temperature of each filament 200 of the filament array 104 rises substantially uniformly corresponds to an activation or heating cycle. During the activation cycle, the filament array 104 prepares to create pores in the skin by heating the filaments 200 in the filament array 104 to or substantially to a desired temperature threshold at which pores through the stratum corneum will be created. As described above, the peak temperatures of lines 807, 808, and 809 are below the maximum temperature 810. Therefore, when the temperature of the filaments 200 reaches the desired temperature threshold (e.g., determined by sensor 224 of control unit 102), control unit 102 can disable current generator 220.

[0117] In some implementations, the current signal has a pulse waveform during the second cycle 804. For example... Figure 8 As shown, the current signal alternates or pulses between "on" and "off". Furthermore, during cycle 804, in response to the pulsed waveform of the current signal, the filament temperature, represented by lines 807, 808, and 809, fluctuates relative to the "on" or "off" state of the current signal line 801. As mentioned above, this is likely due to the current signal passing through the filament 200 and based on the resistance or resistivity of the material of the filament 200. In some embodiments, the slope or rate of the temperature fluctuation shown depends on the material of the filament 200 in the filament array 104. As shown, when the current signal is "on", the temperature of the filament 200 in the filament array 104 increases. When the current signal is "off", the temperature of the filament 200 decreases. Control of the current on and off can be accomplished via a constant programmed sequence of sensors (directly, measuring temperature or resistance, or indirectly, measuring energy and power dispersed in the filament).

[0118] In some embodiments, the period 804 in which the temperature of each filament 200 in the filament array 104 fluctuates in response to a current signal corresponds to a maintenance period when the temperature of the filament 200 is maintained at or near a target temperature. Therefore, when the temperature of the filament 200 drops below a threshold temperature (e.g., determined by sensor 224 of control unit 102), control unit 102 can activate current generator 220. As described above, current generator 220 can be activated until the temperature of the filament 200 reaches the desired temperature threshold, at which point current generator 220 is deactivated. Thus, during maintenance period 804, the filament array 104 is maintained at or near the temperature at which pores are formed in the skin by periodically heating / cooling the filaments 200 in the filament array 104 to or substantially to the desired temperature threshold. Therefore, the activation / deactivation of current generator 220 can be repeated.

[0119] In some embodiments, during the third cycle 806, the current signal is "disconnected" and not received by the filament array 104. During the third cycle 806, cooling of the filaments 200, as indicated by lines 807, 808, and 809, is allowed, with each line gradually decreasing to a relatively constant level at the end of the third cycle 806. In some embodiments, the third cycle 806 corresponds to a shutdown cycle, in which the temperature of the filaments 200 is allowed to be cooled during the "cooling" period. After the cooling cycle, another pulse sequence can be generated to bring the filaments to the desired temperature; this subsequent pulse sequence may be the same as or different from the previous pulse sequence.

[0120] Control unit 102 can control current generator 220 to generate a current signal that produces the filament temperatures of lines 807, 808, and 809 in FIG. 800. Therefore, current generator 220 can generate a current signal to raise the temperature of filament array 104 to an ablation temperature (e.g., 123°C). Current generator 220 can then pulse the current signal to maintain the temperature of filament array 104 within a desired range and / or close to the ablation temperature.

[0121] Figure 9 Figure 900 illustrates the energy delivered to the filament array 104 over time by current and voltage signals (lines 901 and 903, respectively) according to an exemplary embodiment. Figure 900 shows the voltage and current along the y-axis as a function of time along the x-axis. Line 901 represents the current applied to the filament array 104 by the current signal. Line 903 represents the voltage of the filament array 104. Figure 900 also shows four periods or stages 902, 904, 906, and 908.

[0122] Line 901 illustrates the application of a current signal in periodic pulses, with an initial pulse of approximately 100 to 700 μs and subsequent pulses of approximately 800 to 1200 μs, 1300 to 1700 μs, 1800 to 2100 μs, 2300 to 2600 μs, 2700 to 2900 μs, 3000 to 3300 μs, 3400 to 3600 μs, and 3700 to 3900 μs. Each pulse includes a rising, plateauing, and falling phase of the current signal. Line 903 illustrates that the voltage of the filament array 104 also pulses during the periodic pulses of the current signal. During the rising and falling phases of the current signal, the voltage is also considered to rise and fall at corresponding times. During the plateauing phase of the current signal, the voltage is also considered to be plateauing.

[0123] The first stage 902 corresponds to the heating stage, during which the initial current pulse causes the temperature of the filament array 104 to rise, as indicated by the voltage rise during the first stage 902. The second stage 904 corresponds to the deceleration stage, during which the amplitude of the initial current pulse can be reduced to prevent the filaments from failing and breaking (burning out). The third stage 906 corresponds to the sustaining stage, during which subsequent pulses of the current signal (and subsequent pulses of the voltage) occur. The third stage 906 can also correspond to the sustaining stage, during which the current signal is pulsed to maintain the temperature of the filament array 104, thereby enabling ablation. Pulsing occurs during the third stage 906 to ensure that the temperature of the filament array 104 does not exceed the failure temperature of the filament 200 and does not drop below the temperature at which ablation does not occur.

[0124] The third stage 906 also includes two stages 908. The two stages 908 correspond to the temperature regulation cycle. Current 901 and voltage 903 indicate how the system behaves under pre-programmed sustaining pulses (switching). This is good if all the filaments (and the filament array) are made with precise dimensions. If some of them vary due to, for example, the manufacturing process, this energy delivery may be too much or too little, resulting in a rapid temperature runaway or slow cooling, and insufficient energy delivery to create an orifice. Each switch from heating to deceleration to sustaining is controlled by a feedback loop. Once a temperature (or energy) threshold is reached, the system enters the next state. Line 905 illustrates one implementation where sensor 224 determines that the current (or energy) supplied to the filament array should be paused to prevent the filaments from burning out and to maintain a constant temperature. In other words, line 905 illustrates the use of a feedback loop that uses sensor 224 to control the current supplied to the filament array. In this case, this is done twice during the entire pulse sequence used in this example.

[0125] The control unit 102 can control the current generator 220 to generate the current signal shown in FIG900. For example, as mentioned above... Figure 8 The current generator can generate current signals during the initial pulse and during stage 902 to raise the temperature of the filament array 104 to or substantially to the ablation temperature (e.g., 123°C). The current generator 220 can then pulse current signals to maintain the temperature of the filament array 104 within a desired range and / or close to the ablation temperature. These sustaining pulses may correspond to the pulses shown during stage 906. During stage 904, the current generator 220 may keep the current level of the initial pulse off or reduced. The currents during these stages may or may not be of the same amplitude.

[0126] In some embodiments, the control unit 102 of the thermal ablation system 100 is configured to control (e.g., via processor 204) a current generator 220 to generate a current signal having one or more pulses. The current generator 220 may be configured to control the pulse length of the current signal to be greater than or equal to a first pulse length (i.e., a sustaining pulse length) and less than a second pulse length (i.e., a heating pulse length), the second pulse length being greater than the first pulse length.

[0127] In some embodiments, the control unit 102 of the thermal ablation system 100 is configured to control the power supply current value to have a third current density (e.g., the current density during the heating phase) at a first time (during the heating phase). The control unit 102 of the thermal ablation system 100 is configured to control the power supply current value to have a fourth current density (e.g., the current density during the maintenance phase) at a second time (during the maintenance phase), wherein the third and fourth current densities are between or equal to the first current density (e.g., the current density of line A) and the second current density (e.g., the current density of line B). The fourth current density is less than the third current density, and the second time is later than the first time.

[0128] In some implementations, the control unit 102, for example via the processor 204 and / or the current generator 220, can control the current signal and current density during the heating and maintenance phases to enable the stratum corneum to be ablated or perforated to the epidermis while minimizing or reducing the possibility of filament 200 failure.

[0129] In some implementations, the control unit 102, for example via the processor 204 and / or the current generator 220, combines the pulse length of the control current signal and the pulse period between consecutive pulses of the pulse signal to ablate or flash the skin surface while minimizing the possibility of filament failure and melting.

[0130] Figure 10 This illustrates an exemplary implementation. Figure 1A Figure 1000 shows the operating temperature distribution of the filament array 104. Line 1001 represents the operating temperature distribution shown, which generally tracks the temperature change over time as shown by line 1003. Figure 1000 also includes three phases 1002, 1004, and 1006.

[0131] Line 1050 represents the voltage across the filament array, which is switched on or off corresponding to the current-on / off phase. Line 1051 represents the calculated temperature. Phase 1002 is the heating phase at the highest current, and phase 1004 is the deceleration phase at a slightly lower current, so the temperature rises more slowly. Note that line 1050 in segment 1004 is higher than line 1050 in segment 1002, even at lower currents. This is because the resistance of the filament array 104 increases due to the rising temperature. The sharp drop in line 1050 between segments 1002 and 1004 points to the moment (and specific temperature) when the current decreases and the voltage decreases accordingly, but the temperature of the filament remains relatively constant during this short period. Once the desired temperature is reached, the system enters a sustaining phase, where our voltage (line 1050) is constant (corresponding to a constant temperature) and is switched (to the empty line portion).

[0132] Figure 11A and Figure 11B The exemplary embodiments are shown respectively. Figure 1B Figures 1100 and 1150 show the temperature profiles of two different energy delivery curves for the filament array. Figure 1100 illustrates the low-flux energy delivery curve. The low-flux energy delivery curve includes a low-current heating phase followed by a cryogenic threshold phase. The low-flux energy delivery curve can include a low current through the filament array 104, which can cause pain due to the longer pulses used to deliver energy to the skin. Such longer pulses, even at lower currents, can lead to skin charring and occlusion. Alternatively, the low-flux energy delivery curve can utilize a cryogenic threshold that is easier to control but results in even longer pulses because the same energy needs to be delivered in more blocks and lower quality (e.g., shallower) pores.

[0133] Figure 1150 illustrates a high-throughput energy delivery profile. The high-throughput energy delivery profile includes a high-current heating phase followed by a high-temperature threshold phase. The high-throughput energy delivery profile can include a high current passing through the filament array 104, which may lead to runaway effects and cause failure of the filament array 104. However, the high-throughput energy delivery profile can be faster than the low-throughput energy delivery profile and produces better orifices (e.g., deeper orifices). Additionally, the high-throughput energy delivery profile can utilize the high-temperature threshold compared to the low-throughput energy delivery profile, which increases the risk of failure but produces shorter pulses and better orifice performance.

[0134] While keeping power / total energy within the constraints mentioned above, the delivery curve and pulse structure can also affect the quality and size of the aperture. For example, in the curve of Figure 11A, switching is used to ensure the safety of the filament and temperature drop. This switching can help the filament cool slightly. If there is a state with rapid heating (heating cycle 1002) and a high temperature threshold, then only a few switching moments are needed to provide the optimal energy flux to keep the filament safe and to be on the fast side of energy delivery to ensure a more efficient process, including reducing or eliminating pain response and better energy efficiency.

[0135] It may be beneficial to have a high energy flux during the heating phase of the filament array 104 to rapidly deliver the energy required for heating and ablation of the stratum corneum, and then reduce the energy flux to maintain equilibrium with epidermal evaporation. The lower energy flux can be achieved by modulating the current level of the current signal or by modulating the duty cycle of the current signal, or a combination of both. In some embodiments, the feedback system may calculate the resistance of the filament 200 based on electrical measurements from, for example, sensor 224 of the control unit 102, which is proportional to the temperature of the filament 200.

[0136] The feedback system can be implemented by one or more components of the control unit 102. The feedback system operates as follows: an initial current (e.g., generated by current generator 220) is high during a rapid heating phase and is eventually reduced, triggered by the temperature of the filament, as measured by one of the sensors 224, reaching a set target. Following the high initial current is an intermediate phase that moderates (decelerates) the heating rate of the filament 200 to the final temperature. Finally, a sustaining phase allows the current generator 220 and control unit 102 to balance the energy between the current pumped into the filament 200 and the energy used for epidermal evaporation (or pore generation). The current flux is variable in these phases and can be set pulse-by-pulse by the current generator 220. Typically, the current flux is highest during the rapid heating phase and lowest during the sustaining phase due to the filament heating dynamics. The level depends on the number of filaments, the electrical morphology of the array, and the shape of the filament 220. The triggering of the pause / change in current delivery can be achieved by time, the temperature of the filament, the single or cumulative energy delivered, or a combination of these.

[0137] The embodiments described herein assume that the contact between the filament 200 and the skin provides sufficient heat transfer and that the contact is uniform. One way to ensure contact is to design and manufacture the filament 200 with a 3D structure projecting outward toward the skin. The 3D structure of the filament can facilitate better contact with the skin because contact can occur with the surface of the filament 200 rather than the entire surface of the filament array 104. Additionally or alternatively, a vacuum can be introduced, which pulls the skin into contact with or onto the filament 200, as previously described. A vacuum can provide good uniform contact between the skin and the filament 200. In some embodiments, for contact with the filament 200 at a distance of approximately 1 cm... 2 For a perforator with an effective contact area, a minimum vacuum of approximately 5 mm Hg is required to produce a feasible hole based on the aforementioned energy range, where the pulse is not too long and will not jeopardize the filament 200, causing cascading failure.

[0138] To deliver consistent thermal ablation across a range of filament array probe designs, energy delivery from the probe to the skin is closely measured. Embodiments of the present invention aim to directly control the temperature of the filament array at the surface of the skin-probe contact site, and to dynamically adjust energy delivery.

[0139] Those skilled in the art will recognize that the various exemplary logic blocks, modules, circuits, and algorithm steps described below, as well as combinations thereof with the embodiments disclosed herein, can be implemented as electronic hardware, software stored on a computer-readable medium and executable by a hardware processor, or a combination of both. To clearly illustrate this interchangeability between hardware and software, various exemplary components, blocks, modules, circuits, and steps have been generally described above in terms of their functionality. Whether this functionality is implemented as hardware or software depends on the specific application and the design constraints imposed on the overall system. Those skilled in the art may implement the described functionality in different ways for each specific application, but such implementation decisions should not be construed as departing from the scope of the invention.

[0140] The various exemplary logic blocks, modules, and circuits described in conjunction with the embodiments disclosed herein can be implemented or performed using a general-purpose processor, a digital signal processor (DSP), an application-specific integrated circuit (ASIC), a field-programmable gate array (FPGA) or other programmable logic device, discrete gate or transistor logic, discrete hardware components, or any combination thereof designed to perform the functions described herein. The general-purpose processor can be a microprocessor, but alternatively, the processor can be any conventional processor, controller, microcontroller, or state machine. The processor can also be implemented as a combination of computing devices, such as a combination of a DSP and a microprocessor, multiple microprocessors, one or more microprocessors incorporating a DSP core, or any other such configuration.

[0141] The steps of the methods or algorithms described in conjunction with the embodiments disclosed herein can be implemented directly in hardware, as a software module executed by a processor, or a combination of both. The software module can reside in RAM memory, flash memory, ROM memory, EPROM memory, EEPROM memory, registers, hard disk, removable disk, CD-ROM, or any other form of storage medium known in the art. An exemplary storage medium is coupled to the processor, enabling the processor to read information from and write information to the storage medium. Alternatively, the storage medium can be integrated into the processor. The processor and storage medium can reside in an ASIC.

[0142] While the detailed description above has shown, described, and pointed out novel features developed for various embodiments, it should be understood that those skilled in the art can make various omissions, substitutions, and changes in the form and detail of the illustrated apparatus or process without departing from the spirit of the invention. As will be appreciated, the invention may be embodied in forms that do not provide all the features and benefits set forth herein, as some features may be used or practiced separately from others. All variations within the meaning and scope of the equivalents of the claims are included within their scope.

[0143] Those skilled in the art will recognize that each of these subsystems can be interconnected and controllably connected using a variety of technologies and hardware, and that this disclosure is not limited to any particular method of interconnection or connection of hardware.

[0144] This technology can be operated in a variety of other general-purpose or special-purpose computing system environments or configurations. Examples of known computing systems, environments and / or configurations suitable for this invention include, but are not limited to, personal computers, server computers, handheld or laptop devices, multiprocessor systems, microprocessor-based systems, microcontrollers or microcontroller-based systems, programmable consumer electronics, network PCs, minicomputers, mainframe computers, and distributed computing environments including any of the above systems or devices.

[0145] As used herein, an instruction refers to a computer-implemented step for processing information within a system. Instructions can be implemented in software, firmware, or hardware and include any type of programmed steps taken by components of the system.

[0146] The microprocessor can be any conventional general-purpose single-chip or multi-chip microprocessor, such as a Pentium® processor, Pentium® Pro processor, 8051 processor, MIPS® processor, PowerPC® processor, or Alpha® processor. Alternatively, the microprocessor can be any conventional special-purpose microprocessor, such as a digital signal processor or graphics processor. Microprocessors typically have conventional address lines, conventional data lines, and one or more conventional control lines.

[0147] The system can be used with various operating systems, such as Linux®, UNIX®, MacOS®, or Microsoft Windows®, or a custom-designed OS.

[0148] System controls can be written in any common programming language such as C, C++, BASIC, Pascal, .NET (e.g., C#), or Java, and run on a common operating system. C, C++, BASIC, Pascal, Java, and FORTRAN are industry-standard programming languages, and many commercial compilers can be used to create executable code for them. Interpreted languages ​​such as Perl, Python, or Ruby can also be used to write system controls. Other languages, such as PHP and JavaScript, can also be used.

[0149] The foregoing description details certain embodiments of the systems, apparatuses, and methods disclosed herein. However, it should be understood that the systems, apparatuses, and methods can be practiced in various ways, regardless of how the foregoing detailed description appears in the text. Also as noted above, it should be observed that the use of specific terms when describing certain features or aspects of the invention should not be construed as meaning that the term is redefined herein to be limited to include any particular characteristic of the technology or aspect associated with that term.

[0150] Those skilled in the art will understand that various modifications and changes can be made without departing from the scope of the described technology. Such modifications and changes are intended to fall within the scope of the embodiments. Those skilled in the art will also understand that components included in one embodiment may be interchangeable with those in other embodiments; one or more components from the depicted embodiments may be included in any combination with other depicted embodiments. For example, any of the various components described herein and / or in the accompanying drawings may be combined, interchanged, or excluded from other embodiments.

[0151] Regarding the use of virtually any plural and / or singular terms herein, those skilled in the art may translate plural to singular and / or singular to plural, depending on the context and / or the application. For clarity, various singular / plural substitutions are explicitly described herein.

[0152] As used herein, the term “comprising” is synonymous with “including,” “containing,” or “characterized in,” and is inclusive or open-ended, and does not exclude additional, unlisted elements or methodological steps.

[0153] All numerical values ​​used in the specification and claims to indicate the amount of ingredients, reaction conditions, etc., should be understood to be modified with the term "about" in all cases. Therefore, unless otherwise specified, the numerical parameters set forth in the specification and appended claims are approximate values ​​that may vary according to the desired properties sought to be obtained according to the invention. At least, rather than attempting to apply the doctrine of equivalence to the scope of the claims, each numerical parameter should be interpreted according to the number of significant figures and commonly used rounding methods.

[0154] The foregoing description discloses several methods and materials of this development. This development allows for modifications to the methods and materials, as well as changes to the manufacturing methods and apparatus. Such modifications will become apparent to those skilled in the art from the content of this disclosure or the practice of the development disclosed herein. Therefore, this development is not intended to be limited to the specific embodiments disclosed herein, but rather covers all modifications and substitutions within the true scope and spirit of the development embodied in the appended claims.

[0155] As those skilled in the art will understand, in some embodiments, the processes described in the following materials can be performed on a computer network. The computer network has a central server having a processor, data storage (e.g., a database and memory), and communication features that allow wired or wireless communication with various components of the network, including terminals and any other desired network access points or mechanisms.

Claims

1. An apparatus for delivering thermal energy to a biofilm to cause ablation of portions of the biofilm to a depth sufficient to create micropores, the apparatus comprising: A perforator comprising an array of conductive filaments, wherein the perforator is configured to generate heat based on an electric current flowing through the array of conductive filaments and to provide the heat to a biofilm located adjacent to the perforator. as well as A power supply circuit configured to supply the current to the perforator with multiple pulses in a pulse sequence; The device includes a control circuit connected to the power supply circuit, the control circuit being configured to control one or more parameters of the plurality of pulses; The control circuit controls the current values ​​of the plurality of pulses such that the current values ​​are greater than or equal to a first current density and less than or equal to a second current density, wherein the second current density is greater than the first current density; and The control circuit controls the length of the pulse sequence of the plurality of pulses to be greater than or equal to the length of the first pulse sequence and less than the length of the second pulse sequence, wherein the length of the second pulse sequence is greater than the length of the first pulse sequence.

2. The device according to claim 1, wherein the first current density and the second current density are 1.3 mA / μm. 2 Up to 3.56 mA / μm 2 The lengths of the first pulse sequence and the second pulse sequence are 0.5 ms to 16 ms.

3. The device according to claim 1, wherein the control circuit controls the one or more parameters to achieve the perforator heating process.

4. The device according to claim 3, wherein the control circuit controls the one or more parameters to achieve the thermal deceleration process of the perforator.

5. The device of claim 3, wherein the control circuit controls the one or more parameters to achieve the perforator heat maintenance process.

6. The device of claim 1, wherein the one or more parameters include frequency values ​​representing at least a portion of the frequencies of the plurality of pulses.

7. The device of claim 1, wherein the one or more parameters include a pulse width value representing the pulse width of at least one of the plurality of pulses.

8. The device of claim 1, wherein the control circuit controls the current value to have a third current density at a first time and a fourth current density at a second time, the third current density and the fourth current density being between or equal to the first current density and the second current density, the fourth current density being less than the third current density, and the second time being later than the first time.

9. The device of claim 1, wherein the control circuit is further configured to control the value of the current to flash a portion of the biofilm while minimizing the possibility of filament failure and melting.

10. The device according to any one of claims 1 to 9, wherein the control circuit is further configured to determine the supply ratio of current to the cross-sectional area of ​​the conductive filament array, and to control the supply ratio between a first threshold and a second threshold greater than the first threshold.

11. The device according to any one of claims 1 to 8, wherein the control circuit is further configured to control the pulse period between successive pulses of the plurality of pulses to flash a portion of the biofilm while minimizing the possibility of filament failure and melting.

12. The device according to any one of claims 1 to 8, wherein the power supply circuit is further configured to: Monitor the temperature of the conductive filament array, and The temperature of the conductive filament array is controlled to prevent the filaments from failing and melting or entering an open circuit state.

13. The device of claim 12, wherein the power supply is further configured to monitor the temperature of the conductive filament array at least in part based on the resistance of the conductive filament array.

14. The device of claim 12, wherein the power supply is further configured to monitor the temperature of the conductive filament array based at least in part on received sensed temperature information.

15. The device of claim 14, further comprising at least one sensor configured to provide temperature information to the power supply circuit.

16. The device according to any one of claims 1 to 9, wherein the power supply circuit is further configured to determine whether the pressure applied to the biofilm by the conductive filament array is greater than or equal to a first pressure threshold.

17. The device of claim 1, wherein the second pulse sequence length corresponds to the maximum pulse sequence length, and when the length is less than the maximum pulse sequence length, the user of the device experiences painless micro-perforation.

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