Handheld electroporation device and related systems and methods

Abstract

A method of preparing an electroporation device for administering an electroporation therapy includes providing a charging current from at least one battery through a charging circuit to a supercapacitor unit and charging the supercapacitor unit with the charging current. The charging step includes measuring one or more input parameters of the charging current while the charging current is in at least one of a plurality of charging states to charge the supercapacitor unit. The charging step also includes at least one step of transitioning the charging current between the plurality of charging states in response to the one or more measured input parameters. The step of transitioning the charging current includes adjusting a magnitude of the charging current. In this method, the measuring and transitioning steps are automatically controlled by a control unit executing machine-readable instructions.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 314,282, filed in the name of Stadelmann et al. on February 25, 2022, the entire contents of which are incorporated herein by reference.

[0002] The present invention relates to electroporation, and more particularly to an electroporation device for increasing in vivo transfection of injected agents. [Background technology]

[0003] The classical method of administering vaccines and other drugs to body tissues is to inject them directly into muscle or skin tissue using a syringe and needle. It is known that the incorporation of an electroporation pulse of electrical energy at or near the injection site facilitates the direct delivery of such vaccines or drugs to cells in the tissue. Such direct delivery to cells using electroporation electrical pulses may have a more significant clinical effect on the quality of the body's metabolic and / or immune system responses than simple syringe and needle injection. Furthermore, the ability to deliver drugs directly to cells via electroporation has enabled the effective delivery of therapeutic agents (e.g., DNA-encoded monoclonal antibodies (dMAbs), expressible naked DNA encoding polypeptides, expressible naked DNA encoding proteins, recombinant nucleic acid sequences encoding antibodies, etc.) with any number of functions, including antigenicity to induce an immune response, or metabolicity to affect various biological pathways that result in clinical effects.

[0004] Handheld electroporation devices typically require either a wired connection to a power source or a bulky battery assembly to provide sufficient power supply for multiple in vivo electroporation treatments (i.e., multiple patients). Such electroporation devices are less effective in remote treatment environments, such as remote and / or developing countries, where the power grid may be unreliable, require uncommon outlet (e.g., power plug and socket) configurations, and various types of batteries may not be available. Such electroporation devices are also less effective in mass treatment situations where treatment must be administered to a large number of at-risk individuals, such as mass vaccination and / or immunization situations. Such electroporation devices are also less effective for long-term storage and / or stockpiling scenarios, where the device may need to be stored for potentially long periods of time and quickly retrieved to provide reliable treatment. The built-in permanent batteries often used in battery-powered handheld electroporation devices have a limited shelf life and are typically not an option for stockpiling or long-term storage. The ongoing coronavirus pandemic has demonstrated a dire need for battery-powered, handheld therapeutic devices that are mass-producible, easy to use, and function quickly, reliably, and efficiently even during mass use and potentially after long-term storage. Summary of the Invention

[0005] According to one embodiment of the present disclosure, a method of preparing an electroporation device for performing an electroporation therapy includes providing a charging current from at least one battery through a charging circuit to a supercapacitor unit and charging the supercapacitor unit with the charging current. The charging step includes measuring one or more input parameters of the charging current while the charging current is in at least one of a plurality of charging states to charge the supercapacitor unit. The charging step also includes at least one step of transitioning the charging current between the plurality of charging states in response to the one or more measured input parameters. The step of transitioning the charging current includes adjusting a magnitude of the charging current. In this method, the measuring and transitioning steps are automatically controlled by a control unit executing machine-readable instructions.

[0006] According to another embodiment of the present disclosure, a method of using a handheld electroporation device includes providing a charging current from at least one battery to a supercapacitor unit through a charging circuit, the charging circuit and the supercapacitor unit being disposed within a device housing, and charging the supercapacitor unit with the charging current. The charging step includes measuring at least one voltage parameter of the at least one battery and adjusting a magnitude of the charging current to a current magnitude associated with a primary state of charge in response to the at least one measured voltage parameter. The measuring and transitioning steps are automatically controlled by a control unit executing machine-readable instructions. The method also includes discharging an output signal from the supercapacitor unit after the supercapacitor unit is fully charged, converting the output signal into one or more electroporation pulses, and transmitting the one or more electroporation pulses to at least one electrode of the handheld electroporation device.

[0007] According to a further embodiment of the present disclosure, a power supply unit for an electroporation apparatus includes a battery unit configured to be interchangeably connected to a first type battery and a second type battery, and an energy storage unit configured to be interchangeably charged by the first type battery and the second type battery and to discharge at least about 30 Joules of total energy. The power supply unit includes an integrated circuit configured to execute computer readable instructions and a charging circuit in electrical communication with the battery unit and the energy storage unit. The charging circuit is operable under the control of the integrated circuit such that the charging circuit is configured to measure one or more input parameters of a charging current drawn from the battery unit, and further configured to adjust a magnitude of the charging current in response to the measured one or more input parameters while the charging circuit is charging the energy storage unit with the charging current.

[0008] According to a further embodiment of the present disclosure, a handheld electroporation device includes a device housing, at least one electrode connectable thereto, and a battery unit at least partially insertable into the device housing and configured to interchangeably connect to a first type battery and a second type battery. The device includes a supercapacitor unit configured to be interchangeably charged by the first type battery and the second type battery and further configured to discharge at least about 30 Joules of total energy. A charging circuit is in electrical communication with the battery unit and the supercapacitor unit and configured to provide a charging current from the battery unit to the supercapacitor unit to charge the supercapacitor unit. The charging circuit, operating under control of an integrated circuit configured to execute machine-readable instructions, is configured to measure at least one voltage parameter of the respective first type battery or second type battery and, in response thereto, adjust the magnitude of the charging current, thereby reducing the rate at which the respective first type battery or second type battery loses charge during charging of the supercapacitor unit.

[0009] The above summary of the present application, as well as the following detailed description of exemplary embodiments, will be better understood when read in conjunction with the accompanying drawings. For the purpose of illustrating the features of the present application, there are shown in the drawings exemplary embodiments. It is to be understood, however, that the present application is not limited to the precise arrangements and instrumentalities shown. The drawings are as follows: [Brief description of the drawings]

[0010] [Figure 1A] FIG. 1 is a perspective view of a handheld electroporation device according to one embodiment of the present disclosure. [Figure 1B] FIG. 1B is another perspective view of the handheld electroporation device of FIG. 1A, seen from the opposite side. [Figure 2A] FIG. 1B is a partially exploded perspective view of a distal portion of the electroporation device shown in FIG. 1A, showing an electrode array that can be attached to the distal portion of the housing member of the device. [Figure 2B] FIG. 1B is a side plan view of the distal portion of the electroporation apparatus shown in FIG. 1A. [Figure 2C] FIG. 1B illustrates a physician treating a subject using the electroporation device shown in FIG. 1A, according to one embodiment of the present disclosure. [Figure 3A] FIG. 2B is a perspective view of an electrode array assembly including the electrode array shown in FIG. 2A and a safety cap coupled thereto. [Figure 3B] FIG. 3B is a perspective view of the electrode array assembly shown in FIG. 3A disposed within a sterile packaging container according to one embodiment of the present disclosure. [Figure 3C] FIG. 3B is a top view of the electrode array assembly shown in FIG. 3A placed within a sterile packaging container according to one embodiment of the present disclosure. [Figure 3D] FIG. 4 is a perspective view of a bulk packaging assembly including a number of the sterile packaging containers shown in FIGS. 3B and 3C. [Figure 4A] FIG. 1B is a plan view of the opposite side of the handheld electroporation device shown in FIG. 1A with the outer housing member removed to show the internal components of the device. [Figure 4B] FIG. 1B is a plan view of the opposite side of the handheld electroporation device shown in FIG. 1A with the outer housing member removed to show the internal components of the device. [Figure 4C] FIG. 4C is a partial exploded perspective view of the electroporation device shown in FIGS. 4A and 4B, illustrating battery component features of the device and batteries usable with the device, according to one embodiment of the present disclosure. [Figure 4D] FIG. 4C is another partially exploded perspective view of the electroporation device shown in FIGS. 4A and 4B with additional housing members removed for illustration purposes. [Figure 4E] FIG. 4C is an exploded view of the internal components of the electroporation apparatus shown in FIGS. 4A-4D, including a circuit board for connecting the battery components to an energy storage unit. [Diagram 5] FIG. 2 is a diagram of a power supply unit and constituent electrical components for use with the electroporation apparatus shown in FIGS. 1A-4D. [Figure 6] FIG. 1 is a diagram of an algorithm for charging an energy storage unit of a device using a pair of batteries, according to one embodiment of the disclosure. [Figure 7] FIG. 1 is a side plan view of an electroporation system including a handheld electroporation device and a base station according to one embodiment of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] The present disclosure may be more readily understood by reference to the following detailed description, which is provided in conjunction with the accompanying drawings and examples that form a part of this disclosure. It should be understood that the present disclosure is not limited to the specific apparatus, methods, applications, conditions, or parameters described and / or illustrated herein, and that the terminology used herein is for the purpose of describing particular embodiments by way of example only, and is not intended to be limiting of the scope of the present disclosure. Also, as used in this specification, including the appended claims, the singular forms "a," "an," and "the" include the plural, and reference to a particular numerical value includes at least that particular value, unless the context clearly dictates otherwise.

[0012] The term "plurality," as used herein, means more than one. When ranges of values ​​are expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values ​​are expressed as approximations, by use of the antecedent "about," it will be understood that the particular value forms another embodiment. All ranges are inclusive and combinable.

[0013] The terms "approximately," "about," and "substantially," as used herein with respect to dimensions, angles, ratios, and other geometric features, take into account manufacturing tolerances. Additionally, the terms "approximately," "about," and "substantially" may include 10% greater or less than the stated dimension, ratio, or angle. Additionally, the terms "approximately," "about," and "substantially" may be equally applied to the specific values ​​stated.

[0014] Terms such as first, second, etc. may be used herein to describe various elements, but it should be understood that these elements should not be limited by these terms. These terms are used to distinguish one element from another. For example, a first element can be called a second element, and similarly, a second element can be called a first element, without departing from the scope of the embodiments disclosed herein.

[0015] The embodiments disclosed herein relate to devices and methods for storing, charging, and releasing electroporation energy in a relatively small, easy-to-use handheld electroporation device adapted to perform reversible electroporation in vivo. For example, the embodiments herein include handheld electroporation devices and techniques that store energy inside the device at low voltage, yet generate a substantially instantaneous high current for reversibly electroporating tissue. Furthermore, the electroporation devices and techniques described herein have an energy storage unit that can be fully charged in a short time frame (e.g., 3 minutes or less) using common and widely available batteries, which charges the energy storage unit under the control of a control unit that is in the device and is also powered by the battery. These features further help to save overall space in the handheld electroporation device, which can be made small and lightweight compared to state-of-the-art handheld electroporation devices, and also allow the devices herein to be mass-produced on an industrial scale, which is particularly advantageous for mass vaccination type environments. Moreover, the energy storage, charging, and discharging features described herein allow the electroporation device to be stored in a long-term reserve setting, yet be removed and used virtually immediately using widely available off-the-shelf battery types. When incorporated into the handheld electroporation device described herein, these features provide a compact, self-contained, storable, widely usable, and mass-producible handheld electroporation device. These features are facilitated by an algorithm uniquely adapted to instruct the control unit to extract substantially maximum energy from the battery with substantially highest efficiency to charge the energy storage unit, without adversely affecting the power supply to the control unit. In other words, the algorithm substantially optimizes the maximum allowable current drawn from the battery unit while maintaining an acceptable operating voltage for the electronic control circuitry to operate.The algorithm also provides the added safety benefit of adjusting the charging current to provide a highly efficient charging profile, protecting the battery from overload, overheating, inefficient or insufficient power output, fire and / or other potential damage.

[0016] 1A-1B, an exemplary embodiment of a battery-powered, handheld electroporation device 2 is shown. The device 2 includes a handle body 4 having a proximal end 6 to a distal end 8 spaced apart from one another along a longitudinal direction X. The handle body 4 is configured to carry at least one electrode 10 at the distal end 8. In the illustrated embodiment, the handle body 4 is configured to carry a plurality of electrodes 10, specifically three (3) electrodes 10 arranged in a triangular pattern. In other embodiments, the handle body 4 may be configured to carry two (2) electrodes 10. In additional embodiments, the handle body 4 may be configured to carry other quantities of electrodes 10, such as four (4), five (5), six (6), seven (7), eight (8), nine (9), ten (10), eleven (11), twelve (12), or more than twelve electrodes 10. In embodiments with multiple electrodes 10, the electrodes 10 can be arranged in various patterns, such as, by way of non-limiting example, circular, polygonal, concentric, grid, irregular patterns, etc. In other embodiments, the handle body 4 can be configured to carry a single electrode 10. Thus, while the following description refers to multiple electrodes 10, it should be understood that the present disclosure encompasses embodiments having a single electrode 10. The electrode 10 is configured to deliver one or more pulses of electrical energy to cells of a target tissue in vivo, particularly to reversibly electroporate the cells. Any such electrical pulses can be referred to as "electroporation pulses." The device 2 includes a power supply unit 12 and circuitry for providing electrical communication between the power supply unit 12 and the electrodes 10 and for generating and transmitting one or more electroporation pulses to the electrodes 10, as described in more detail below.

[0017] The handle body 4 includes one or more housing members 14, 16 that define the handle body 4 and house the internal components of the device 2. In the illustrated embodiment, the handle body 4 includes a first housing member 14 that extends in a distal direction D from the proximal end 6 to the distal end 8, and a second housing member 16 located at the distal end 8. The distal direction D is opposite the proximal direction P. It should be understood that the distal direction D and the proximal direction P are each unidirectional components of the longitudinal direction X, which is bidirectional. It should also be understood that, as used herein, the terms "longitudinal" and "longitudinally" and their derivatives refer to the longitudinal direction X. The terms "distal" and "distally" and their derivatives refer to the distal direction D. The terms "proximal" and "proximal" and their derivatives refer to the proximal direction P. The first housing member 14 houses the power supply unit 12 and additional internal components of the device 2. The second housing member 16 is configured to receive the electrode 10. The first and second housing members 14, 16 define respective openings, access ports, openings, etc. for additional components of the device 2, such as user interface components, as described in further detail below. It should be understood that the first and second housing members 14, 16 may be collectively referred to as the "device housing" 14, 16. It should also be understood that in other embodiments, the handle body 4 may employ other device housing configurations, such as a clamshell device housing configuration, a one-piece device housing configuration, or other device housing configurations.

[0018] 2A-2B, the distal end 8 of the handle body 4 includes an electrode mount 30 for receiving an electrode 10. In the illustrated embodiment, the electrode mount 30 is provided on the second housing member 16. The electrode 10 is carried by an electrode applicator 32, which together with the electrode 10 can be referred to as an "electrode array" 34. The electrode applicator 32 carries the electrode 10 such that the distal end 13 of the electrode 10 extends forward from a front surface 33 of the electrode applicator 32 and the proximal end 15 of the electrode 10 extends rearward toward the handle member 4. The electrode array 34 and the electrode mount 30 have complementary geometric shapes that allow the electrode array 34 to be removably attached to and detached from the electrode mount 30. In particular, the electrode mount 30 can be received within and coupled to a rear receptacle 35 of the electrode applicator 32 (see FIG. 3A). The proximal end 15 of the electrode 10 is receivable within a socket 17 defined in the electrode mount 30 to provide electrical communication between the electrode 10 and the circuitry of the device 2 .

[0019] The electrode mount 30 and the electrode array 34 preferably include complementary locking structures for securely attaching the electrode array 34 to the electrode mount 30. In the illustrated embodiment, the locking structures include a locking post 36 disposed on the electrode mount 30 and a complementary locking arm 38 defined by the electrode applicator 32. The locking arm 38 defines a locking slot 40 configured to receive the locking post 36 of the electrode mount 30 and couple thereto, such as in a snap-fit ​​manner. In this manner, the interlocking engagement of the locking post 36 and the locking arm 38 prevents the electrode applicator 32 from being unintentionally separated from the electrode mount 30. The locking arm 38 may extend outwardly from the electrode applicator 32 and includes a release tab 42 configured to allow a user to flex the locking arm 38 outwardly in a manner that disengages the locking post 36 from the locking slot 40, thereby allowing the user to remove the electrode applicator 32 from the electrode mount 30 as needed, such as between uses. In this manner, the device 2 can be configured for disposable electroporation applications, allowing the physician to remove the used electrode array 34 after each use and install a new electrode array 34 for the next treatment subject. The used electrode array 34 can be discarded or sterilized for subsequent use.

[0020] As shown in FIG. 2B, the electrode applicator 32 carries the electrode 10 at a maximum electrode depth L1 measured from the distal end 13 of the electrode 10 to the front surface 33 of the electrode applicator 32. In the illustrated embodiment, the maximum electrode depth L1 is configured for intradermal (ID) electroporation and is in the range of about 0.01 mm to about 5.0 mm. It should be understood that in other embodiments, the electrode 10 can be configured for intramuscular (IM) electroporation and can have a maximum electrode depth L1 in the range of about 5.0 mm to about 35 mm. In yet other embodiments, the electrode 10 can be configured for adipose electroporation and can have a maximum electrode depth L1 in the range of about 4.0 mm to about 20 mm. In further embodiments, the electrode 10 can be configured for multi-depth electroporation, such as targeting any combination of intradermal, adipose, intramuscular, and / or mucosal tissue.

[0021] In the illustrated embodiment, the electrode mount 30 positions the electrode array 34 at an application angle A1 from a longitudinal axis 37 of the device 2, which is oriented along the longitudinal direction X. For purposes of this disclosure, the application angle A1 is defined as the angle extending from (1) a location on the longitudinal axis 37 spaced distally from the distal end 8 of the handle body 4 to (2) a central axis 39 of the electrode array 34. The application angle A1 is in the range of about 0 degrees to about 90 degrees, more specifically about 45 degrees to about 80 degrees, and more specifically about 55 degrees to about 65 degrees. As shown in FIG. 2C, the application angle A1 provides the device 2 with an ergonomic design that is advantageously adapted to treat a subject.

[0022] 3A, the electrode array 34 can be placed in a removable safety cap 44 configured to cover the electrodes 10 prior to treatment. The electrode array 34 and the safety cap 44 together comprise an array assembly 43. The cap 44 preferably includes one or more gripping features 46 to facilitate handling by a user, such as for mounting the electrode array 34 to the mount 30. As shown, the mount 30 can include a guide member 31a, such as a guide slot 31a, that receives a complementary guide member 31b of the applicator 32, such as a guide protrusion 31b, to facilitate proper alignment of the proximal end 15 of the electrode 10 with the socket 17 of the mount 30 during mounting of the applicator 32. It should be understood that the cap 44 and the applicator 32 of the illustrated embodiment can be cooperatively connected to one another in a manner that prevents inadvertent separation from one another. The coupling forces between the cap 44 and the actuator 32 are configured to be easily overcome when the applicator 32 is attached to the mount 30, thereby facilitating removal of the cap when the device 2 is ready for treatment.

[0023] As shown in FIGS. 3B-3C, the array assembly 43 may be provided in a separate sterile packaging container, such as the illustrated "tray" type container 48. In other embodiments, the array assembly 43 may be provided in a sterile peel pouch container, a sterile blister type container, or other type of sterile container. As shown in FIG. 3D, the tray type containers 48 may be advantageously nested together for bulk packaging. It should be understood that the electrode array 34 is preferably configured for a single-use treatment. For such a single-use treatment, the physician removes the array assembly 43 from the sterile packaging container and attaches the array assembly 43 to the mount 30. In the illustrated embodiment, during attachment, the physician aligns the guide projections 31b of the applicator 32 with the guide slots 31a of the mount 30 to facilitate insertion of the electrode proximal end 15 into the socket 17. The physician pushes the applicator 32 toward the mount 30 until the locking posts 36 of the electrode mount 30 engage the locking slots 40 of the locking arms 38. This coupling may be indicated by an audible and / or tactile "click" or "snap." After the array assembly 43 is coupled to the mount 30 (and preferably the device 2 is ready for treatment), the physician can remove the safety cap 44 and administer the electroporation treatment.

[0024] 4A-4E, the power supply unit 12 includes a battery unit 50, an energy storage unit 70, a charging circuit 80 providing electrical communication between the battery unit 50 and the energy storage unit 70, and a control unit 90 configured to control operation of the charging circuit 80 to transfer charge from the battery unit 50 to charge the energy storage unit 70 with sufficient energy to deliver one or more electroporation pulses to in vivo tissue. As shown, the charging circuit 80 is disposed on a circuit board, which may be a printed circuit board (PCB) 82. The power supply unit 12 also includes user interface components including a power button 18 for turning the device on and off, an electroporation delivery trigger or button 20, an access hub 22, and one or more indicator devices, such as LED displays 24, 25, 26 and / or speaker(s) 28 (see FIGS. 1A and 1B) for indicating various status information of the device 2, as described in more detail below. For example, the indicator device of the illustrated embodiment may be positioned adjacent to the power button 18 and includes a power LED display 25 that indicates when the power button 18 has been activated to turn on the device. The power LED display 25 is preferably a multi-color LED display and is preferably configured to also indicate charge status information for the energy storage unit 70 (i.e., the charge status of the energy storage unit 70). The indicator device of the illustrated embodiment also includes a treatment LED display 26 that may be positioned adjacent to the electrode mount 30 and is configured to indicate a treatment status of the device 2 (e.g., when the device 2 is in a "treatment ready" state, meaning that the device 2 is ready to deliver one or more electroporation pulses).

[0025] The battery unit 50 includes a battery housing 52 that is at least partially receivable within the device housing 14, 16. For example, as shown in FIG. 4C, in the illustrated embodiment, the battery housing 52 includes a proximal end 54 and an insert portion 56 extending distally from the proximal end 54 and partially insertable into the first housing member 14 through a proximal access opening 19 thereof. As shown in FIG. 4D, the insert portions 56 define one or more battery receptacles 58 each configured to hold a battery 60, as described in more detail below. As shown in FIG. 4E, each battery receptacle 58 includes an output terminal 62 configured to electrically communicate with the charging circuit 80, for example, via a respective contact 63 on a PCB 82. In the illustrated embodiment, the battery housing 52 includes a base support member 64, such as a ring stand 64, that extends around the periphery of the proximal end 54. The base support member 64 is configured to allow the device 2 to be freestanding on the proximal end 54.

[0026] As shown in FIG. 4D , in the illustrated embodiment, the battery housing 52 also includes an access hub 22 disposed adjacent the proximal end 54 of the battery housing 52 and accessible through a proximal opening 65 defined by a base support member 64. The access hub 22 includes a battery cover 66 that cycles between a closed position ( FIG. 1B ) in which the battery 60 in the battery receptacle 58 is secured in place and in contact with the output terminals 62, and an open position in which the battery 60 can be inserted into and / or removed from the battery receptacle 58. As shown, the battery cover 66 may be a swing latch type cover, although other types of covers are within the scope of the present disclosure. The access hub 22 also includes an electronic port 67, such as a USB-C port 67, that can be configured to provide electronic communication with an external computing device, such as for charging one or more batteries 60 and / or for monitoring the operation and / or status of the device 2. The access hub 22 may include an indicator device, such as a battery charging LED display 24, for indicating when the battery 60 is charging via an electronic port 67. The access hub 22 may also include an additional port 68 that may provide access to the interior of the first housing member 14. For example, as a non-limiting example, the additional port 68 may provide access to one or more tools for accessing an internal speaker 28 (FIG. 1B), which may be configured to provide an audible indication, such as when the device 2 is fully charged and / or when it is ready for therapy. It should be understood that the additional port 68 may be used for other purposes.

[0027] With continued reference to FIG. 4C, the insert portion 56 of the battery housing 52 includes one or more battery receptacles 58 configured to interchangeably hold at least two types of batteries 60. As used herein, the term "interchangeably" means "at different times" or "on different occasions" without requiring any reconfiguration to be made to the support component(s). For example, with respect to the battery receptacle 58, when it is said that the battery receptacle 58 is configured to interchangeably hold at least two types of batteries 60, it means that in one case, the battery receptacle 58 is configured to hold a first type of battery (such as an alkaline battery) and in another case, it is also configured to hold a second type of battery (such as a nickel metal hydride (NiMH) battery) without requiring any reconfiguration of the battery receptacle 58 or the support component(s) of the battery housing 52. Such battery interchangeability allows users to select different types of batteries, which can be a significant advantage, especially in areas where battery availability is limited. Additionally, as used herein, the phrases “battery type” and “battery type” refer to the type of battery cell chemistry, i.e., alkaline, nickel metal hydride (NiMH), lithium ion (Li-Ion), nickel zinc (NiZn), nickel cadmium (NiCd), etc.

[0028] The battery receptacles 58 are configured to hold batteries of a particular size and a particular battery type. In the illustrated embodiment, the battery housing 52 has two (2) battery receptacles 58, each configured to hold an AA-size battery. As such, each battery receptacle 58 is configured to interchangeably hold an AA-size alkaline battery 60 (e.g., 1.5 volt) and an AA-size nickel metal hydride (NiMH) battery 60 (e.g., 1.25 volt). In other embodiments, one or more battery receptacles 58 may each be configured to interchangeably hold one or more additional battery types, such as, by way of non-limiting example, an AA-size lithium (e.g., lithium ion (Li-ion)), zinc carbon, nickel zinc (NiZn), and nickel cadmium (NiCd). It should be understood that in other embodiments, the battery receptacles 58 may be configured to hold batteries of various types and / or sizes. For example, by way of non-limiting example, in other embodiments, one or more battery receptacles 58 may each be configured to hold other battery sizes, such as AAAA size, AAA size, B size, C size, D size, 9 volt, or various coin cell sizes. In additional embodiments, by way of non-limiting example, battery receptacle(s) 58 may be configured to hold batteries having different sizes, such as AAAA size, AAA size, AA size, B size, C size, D size, 9 volt, as well as alkaline, NiMH, zinc carbon, lithium (e.g., Li-ion), lithium iron phosphate (LiFePO 4It should be appreciated that the battery receptacle 58 may also include a sizable (e.g., compliant) mechanism for interchangeably holding batteries having different battery types, such as lithium-ion polymer (e.g., LiPo), nickel-zinc (NiZn), nickel-cadmium (NiCd), and lead-acid (e.g., sealed lead-acid (SLA) and valve-regulated lead-acid (VRLA)). As used herein with respect to a battery or battery type, the term "preselected" means that such battery or battery type is usable in the battery receptacle 58. Thus, when the following description refers to a "preselected" battery or batteries, such battery or batteries are usable within the battery receptacle 58.

[0029] The control unit 90 shown in FIG. 4A controls the charging circuit 80 to provide charge from the battery unit 50 to the energy storage unit 70. In particular, the control unit 90 is configured to operate the charging circuit 80 to be powered by the battery 60 and to direct charge from the battery 60 to the energy storage unit 70 in a manner that enhances charging of the energy storage unit 70. The energy storage unit 70 includes at least one energy storage device 72, such as, by way of non-limiting example, a supercapacitor, a battery, a capacitor, a plurality of any such storage devices, and / or various combinations of the foregoing. The at least one energy storage device 72 can have a total capacitance (or total equivalent capacitance) in the range of about 0.01 Farads to about 250 Farads, more specifically in the range of about 0.15 Farads to about 7.5 Farads, and more specifically in the range of about 1.20 Farads to about 1.30 Farads.

[0030] The at least one energy storage device 72 is configured to emit an output signal having sufficient energy to electroporate tissue in vivo. In particular, the at least one energy storage device 72 is configured to emit a plurality of energy pulses having sufficient energy to be converted by downstream component(s) into electroporation pulses. These energy pulses can be delivered in various pulse groups (i.e., sequences) configured to provide respective electroporation treatments. As used herein, the terms "pulse group" and "pulse sequence" refer to energy pulse groups having sufficient energy to electroporate tissue in vivo. It should be understood that each such pulse group or pulse sequence is configured to provide a respective electroporation treatment to a patient. It should also be appreciated that each such pulse group or pulse sequence can include a range of pulse amounts from one pulse (single pulse) to two (2) pulses, three (3) pulses, four (4) pulses, five (5) pulses, six (6) pulses, seven (7) pulses, eight (8) pulses, nine (9) pulses, ten (10) pulses, and greater than ten. It should further be appreciated that, by way of non-limiting example, each such pulse group or pulse sequence can include one or more additional energy pulses that lack sufficient energy to electroporate tissue, but serve other purposes of the electroporation treatment, such as measuring impedance or other parameters to provide active feedback information to the control unit 90.

[0031] In this regard, the at least one energy storage device 72 is configured to emit various output signals having energy characteristics useful for providing electroporation therapy. For example, the at least one energy storage device 72 can be configured to emit one or more energy pulses, each having an energy in a range of about 0.004 Joules to about 4.5 Joules. The at least one energy storage device 72 can also be configured to emit pulse sequences (for electroporation therapy), each pulse sequence having a total energy in a range of about 0.015 Joules to about 15.0 Joules. It should be appreciated that the energy magnitude of the output signal can be adjusted as needed to tailor the pulse sequence for electroporating various types of tissue, including skin, fat, muscle, and mucosal tissue.

[0032] In the illustrated embodiment, the energy storage unit 70 comprises a plurality of supercapacitors 72, specifically a pair of supercapacitors 72 connected in series to increase the voltage of the stored charge. In the illustrated embodiment, the supercapacitors 72 each have a capacitance of about 1.25 Farads and a maximum voltage of about 6.0 Volts, so that when connected in series, the supercapacitors 72 have a total capacitance of about 1.25 Farads and a total voltage of about 12.0 Volts. One advantage of using one or more supercapacitors 72 as the energy storage unit 70 is that the supercapacitor can rapidly discharge substantially all of its stored energy. Thus, the supercapacitor 72 of the illustrated embodiment can rapidly discharge an output signal having a total energy of about 90 Joules, various percentages (and up to substantially all) of which can be converted into electroporation pulses. In other embodiments, the energy storage unit 70 can be configured to emit an output energy signal having a total energy in the range of about 7 Joules to about 150 Joules. Thus, in embodiments of the present disclosure, the energy storage unit 70 can be configured to emit an output energy signal having a total energy of at least about 7 Joules, at least about 10 Joules, at least about 20 Joules, at least about 30 Joules, at least about 40 Joules, at least about 50 Joules, at least about 60 Joules, at least about 70 Joules, at least about 80 Joules, at least about 90 Joules, at least about 100 Joules, at least about 110 Joules, at least about 120 Joules, at least about 130 Joules, at least about 140 Joules, at least about 150 Joules, and even greater values. It should be understood that other various supercapacitor configurations and values ​​(e.g., capacitance and voltage) are within the scope of the present disclosure. It should also be understood that when the energy storage unit 70 includes one or more supercapacitors 72, the one or more supercapacitors 72 can be referred to as a "supercapacitor unit" 72.

[0033] The control unit 90 executes machine-readable instructions including an algorithm 100 (FIG. 6) adapted to extract substantially maximum energy (e.g., highest charging current) with the highest efficiency from the battery 60 (regardless of the preselected type of 60 inserted into the battery housing 52) to charge the supercapacitor 72 without adversely affecting the operation of the control unit 90, which is also powered by the battery 60. This configuration is particularly advantageous for a number of reasons. One reason is that the supercapacitor 72 can store energy at low voltage and generate substantially instantaneous high currents useful for generating electroporation pulses. Another reason is that the supercapacitor 72 has a significantly higher energy storage capacity (e.g., several farads) compared to normal capacitors that store energy in microfarads. The lower voltage of the supercapacitor 72 compared to normal capacitors can be partially mitigated by connecting the supercapacitors 72 in series. A further advantage is that by storing energy at a low voltage using supercapacitors 72, overall space within the device 2 is saved, which allows the size of the device 2 to be smaller compared to state-of-the-art electroporation devices, allowing mass production of the device 2 on an industrial scale (i.e., in large quantities), which is particularly advantageous in mass vaccination type environments. Yet another advantage of the device 2 according to the illustrated embodiment is that the device 2 can be stored for long periods in a stockpile type environment, yet can be used with the pre-selected, widely available, off-the-shelf battery types mentioned above, which can be easily purchased by end users in most parts of the world. Yet another advantage is that the algorithm 100 extends the life of the battery by increasing the efficiency with which energy is drawn from the battery, and also provides an additional safety benefit by protecting the battery from overload, overheating, inefficient or insufficient power, fire, and / or other potential damage. Yet another advantage of using a replaceable battery is that the user can charge the battery externally and be prepared to replace used batteries within the device 2 as needed, such as in high-use scenarios such as mass vaccination environments.These advantages are effectively combined to provide a compact, self-contained, storable, and widely usable handheld electroporation device 2. It should be understood that the device 2 herein can be stored without a battery to prevent battery leakage.

[0034] It should also be appreciated that the power-related advantages discussed above result in a smaller size and lighter weight for the device 2 compared to prior art devices. These size and weight savings allow the device 2 to have enhanced ergonomic features that, when combined with the size and weight savings, provide additional ease-of-use advantages, particularly in high-use environments such as mass vaccination environments. These ease-of-use advantages include reduced operator fatigue. In particular, it has been observed that the application angle A1 of the delivery trigger 20 and the pistol grip design allow the user's wrist to be held substantially perpendicular to the patient's arm during treatment, thereby reducing strain on the user's wrist. The device 2 of the illustrated embodiment also allows for better visibility of the treatment site (e.g., injection bleb) because a majority of the device 2 (e.g., first housing member 14) is substantially perpendicular to the treatment site and the electrode array 34 tapers distally. These features improve visibility of the drug injection site and allow for better placement of the electrode(s) 10 at the center of the injection bleb. The device 2 can be held by the user in both sitting and standing positions, again reducing fatigue on the user's wrists, etc. These features have been observed to make it easier for the user to maintain the electrode(s) 10 at the proper insertion angle and depth within the patient's tissue. It should be appreciated that during treatment, the electroporation pulse(s) typically cause the patient's muscles to contract with each pulse, flexing the patient's arm. Therefore, for optimal treatment, it is important for the user to maintain the electrode(s) 10 at the proper insertion depth within the target tissue. For example, a small amount of retraction of the electrode(s) can reduce the impedance caused by the tissue, thereby increasing the current of the electrode 10, which can lead to transfection failure and a potential burning sensation at the electrode insertion point. The light weight, appropriate size, and ease of maintaining the insertion depth and application angle A1 can more easily avoid the aforementioned challenges.

[0035] 5, the charging circuit 80 of the illustrated embodiment includes the battery unit 50, the supercapacitor 72, and a control unit 90. The control unit 90 performs a current regulator 84 operation to control the current drawn from the battery 60 to supply the supercapacitor 72 (referred to herein as the "charging current"). The charging circuit 80 may also include at least one boost regulator 86 disposed between the battery unit 50 and the supercapacitor 72 to increase (e.g., "boost") the voltage of the battery signal supplied to the supercapacitor 72. Such boost regulator(s) 86 may be used to boost the voltage from the battery voltage to a boosted voltage, which is preferably substantially equivalent to the voltage of the supercapacitor 72 when fully charged, which may be referred to as the "full voltage of the supercapacitor." As a non-limiting example, the boosted voltage may be in the range of about 5.0 volts to about 20.0 volts, more specifically in the range of about 10.0 volts to about 14.0 volts, and more specifically in the range of 11.5 volts to about 12.5 volts. In one specific, non-limiting example, the target boost voltage is between about 11.7 volts and about 12 volts, which can be adjusted to suit the voltage capacity of the plurality of supercapacitors 72.

[0036] In additional embodiments, the charging circuit 80 may include at least one additional boost regulator 88. In such embodiments, the additional boost regulator 88 may be disposed between the battery unit 50 and the boost regulator 86. In such embodiments, the additional boost regulator 88 may be referred to as a "first boost regulator" 88, and the other may be referred to as a "second boost regulator" 86. Furthermore, the first boost regulator 88 may be said to boost the voltage of the charging current from the battery voltage to a first boost voltage, and the second boost regulator 86 may be said to boost the voltage of the charging current from the first boost voltage to a second boost voltage (i.e., the full voltage of the supercapacitor). It should be understood that boost regulators tend to operate more efficiently at higher input voltages. Thus, the use of the first and second boost regulators 88, 86 may increase the efficiency of the second boost regulator 86, which boosts the voltage to the full voltage of the supercapacitor. As a non-limiting example, the second boosted voltage can be within the ranges described above for boosted voltages, and the first boosted voltage can be in the range of about 2.0 volts to about 10.0 volts, more specifically in the range of about 3.5 volts to about 7.0 volts, and more specifically in the range of 4.8 volts to about 5.6 volts. In one particular non-limiting example, the first boosted voltage is about 5.2 volts and the second boosted voltage is about 11.84 volts.

[0037] The first and second boost regulators 88, 86 are arranged along a first main branch 85 of the charging circuit 80 extending from the battery unit 50 to the energy storage unit 70. The control unit 90 is arranged along a second control branch 87 of the charging circuit 80 extending from the battery unit 50 to the control unit 90 and parallel to the first branch 85. It should be understood that the current regulation 84 can be performed by a second boost regulator 86 controlled by the control unit 90. In the illustrated embodiment, the control branch 87 includes a control unit boost regulator 89 interposed between the battery unit 50 and the control unit 90. The control unit boost regulator 89 is configured to boost the voltage along the control branch 87 from the battery voltage to a boosted control voltage, the boosted control voltage being at least equal to a minimum operating voltage of the control unit 90. The boost control voltage can be in the range of about 1.7 volts to about 7.0 volts, more specifically in the range of about 2.0 volts to about 5.0 volts, and more specifically in the range of about 3.0 volts to about 3.5 volts. In one particular non-limiting example, the boost control voltage is about 3.3 volts.

[0038] The control unit 90 may include an integrated circuit 92, which may include a processor 94, such as a microprocessor 94, for executing machine-readable instructions (e.g., algorithms) and performing current regulator 84 operations for controlling the charging current of the battery signal provided to the supercapacitor 72. The control unit 90 may also include a computer memory 96 for storing the machine-readable instructions. The computer memory 96 is in electrical communication with the processor 94 and may be incorporated into the integrated circuit 92. The integrated circuit 92 may be, as a non-limiting example, a 32-bit ARM core type microcontroller.

[0039] The supercapacitor unit 72 outputs the charged electrical energy stored therein (e.g., at the full voltage of the supercapacitor) as an output signal that is sent to downstream components that condition the output signal into an electroporation signal. One such downstream component is a high voltage supply booster 98 that boosts the voltage of the output signal (e.g., the full voltage of the supercapacitor) to an electroporation voltage, which may be in the range of about 5 volts to about 1000 volts (1 kV), more specifically in the range of about 100 volts to about 400 volts, and more specifically in the range of about 175 volts to about 250 volts. In one particular, non-limiting example, the electroporation voltage is in the range of about 190 volts to about 210 volts. Additional downstream components include a safety circuit, one or more fuses, additional current (amperage) regulators, an active feedback circuit, and a pulse switch matrix for controlling the pulse firing patterns of the electrodes 10, which are described in more detail below. The one or more electroporation pulses delivered to the electrode 10 can have a current magnitude in the range of about 0.01 amperes to about 2.0 amperes, more specifically in the range of about 0.05 amperes to about 0.5 amperes, more specifically in the range of about 0.15 amperes to about 0.25 amperes. The one or more electroporation pulses can each have a pulse duration in the range of about 100 microseconds (μs) to about 500 milliseconds (ms), more specifically in the range of about 1.0 milliseconds (ms) to about 100 milliseconds (ms), more specifically in the range of about 40 milliseconds (ms) to about 60 milliseconds (ms). The amount of electroporation pulses can be in the range of 1 pulse to about 10 pulses, more specifically in the range of about 3 pulses to about 5 pulses. When multiple pulses are delivered, each electroporation pulse can be separated in time from an adjacent pulse by a pulse delay in the range of about 1 millisecond to about 5 seconds.

[0040] It should be appreciated that in embodiments with multiple electrodes, one or more electroporation pulses can be delivered according to different pulse firing patterns in which different pulses in a pulse sequence are delivered to different predefined electrodes 10. In one particular non-limiting example, the device 2 has three (3) electrodes spatially arranged in a triangular pattern. In this particular example, the electroporation pulses are delivered in a series of pulses, during each pulse of the sequence, one of the electrodes 10 is positive or "active" (i.e., delivers a pulse to tissue), one of the electrodes 10 is negative (i.e., a return electrode), and the remaining electrodes 10 are floating or neutral (e.g., can be used to measure impedance to provide feedback). In such an example, the pulse firing pattern can use different electrodes 10 as the positive, negative, and neutral electrodes 10 for successive pulse(s) in the pulse sequence. In other exemplary embodiments, the pulses in a pulse sequence can be delivered from two positive electrodes to a single negative electrode. In yet another exemplary embodiment, the pulses in a pulse sequence can be delivered from one positive electrode to two negative electrodes. In further exemplary embodiments, the device 2 can have four or more electrodes 10. In such embodiments, any pulse in the pulse sequence can utilize one or more positive electrodes 10, one or more negative electrodes 10, and one or more neutral electrodes 10. It is understood that the output signal emitted by the supercapacitor unit 72 can be adjusted as necessary by downstream components to provide any desired pulse firing pattern via the electrodes 10.

[0041] In one specific, non-limiting example of the illustrated embodiment, the device 2 has three (3) electrodes 10 that deliver a series of four (4) electroporation pulses, each having a voltage within a range of about 180 volts to about 220 volts, a current magnitude within a range of about 0.18 amps to about 0.22 amps, a pulse duration within a range of about 40 milliseconds (ms) to about 60 milliseconds (ms), and an interpulse delay between the pulses within a range of about 200 milliseconds (ms) to about 3.5 seconds. It is understood that various other pulse parameters (e.g., voltage, current magnitude, pulse duration, and interpulse delay) are within the scope of the present disclosure. It is also understood that the device 2 can be configured to deliver one or more additional non-electroporation pulses prior to and / or between the electroporation pulse(s). One such example of a non-electroporation pulse includes the delivery of one or more impedance pulses to provide feedback data to the control unit 90 (i.e., to measure impedance in the target tissue), which interprets the feedback data and adjusts the electroporation pulse(s) in real time, thereby providing a feedback mechanism for the device 2. Such feedback data can be used to maintain a constant current magnitude of the electroporation pulse(s) delivered to the tissue, as more fully described in International Publication No. WO2008 / 048632, published on April 24, 2008, and entitled “ELECTROPORATION DEVICES AND METHODS OF USING SAME FOR ELECTROPORATION OF CELLS IN MAMALS” (the “632 Reference”), and / or can be used to determine the type of tissue (e.g., skin, fat, muscle) in contact with the electrode tip, as more fully described in U.S. Pat. No. 10,610,684, published on April 7, 2020, and entitled “VARIABLE CURRENT DENSITY SINGLE NEEDLE ELECTROPORATION SYSTEM AND METHOD” (the “684 Reference”), the entire disclosures of each of which are incorporated herein by reference.

[0042] 6, an example of an algorithm 100 for charging an energy storage unit 70 from a battery 60 is shown. The algorithm 100 is specifically configured to instruct the control unit 90 to operate the charging circuit 80 to optimize charging of an energy storage unit 70, such as a supercapacitor 72 (or, in other embodiments, a bank of capacitors, a battery, or a combination of the above). The algorithm 100 instructs the control unit 90 to efficiently extract maximum energy (maximum charging current in the illustrated example) from the battery 60 without allowing the charging voltage to drop below the minimum operating voltage of the control unit 90 (e.g., about 3.3 volts in the non-limiting example above). The algorithm 100 also instructs the control unit 90 to communicate various indication signals or outputs to the user indicative of various charging states of the device 2. These indication outputs include optical outputs via the power LED 25 and the treatment LED 26, and can optionally include one or more audible outputs via the speaker 28 (see FIGS. 1A and 1B).

[0043] It should be understood that the exemplary algorithm 100 shown in FIG. 6 is tailored according to one non-limiting exemplary implementation of the present disclosure. In particular, this non-limiting implementation involves charging an energy storage unit 70 having a pair of supercapacitors 72 connected in series from a pair of AA size batteries 60, which may be a pair of replaceable NiMH batteries or a pair of alkaline batteries. Moreover, the algorithm 100 is specifically tailored to charge the supercapacitors 72 using these multiple types of batteries 60 (NiMH and alkaline) and adjust the charging current according to the charge level of the batteries 60. The following description of the algorithm 100 makes particular reference to the illustrated embodiment of the algorithm 100 based on the non-limiting implementation, but it should be understood that various features of the algorithm 100 can be tailored to the implementation and / or other implementations while remaining within the scope of the present disclosure. For example, by way of non-limiting example, the illustrated embodiment of algorithm 100 is adapted for use interchangeably with AA-size NiMH and alkaline batteries, although algorithm 100 can be adapted for use with other power output requirements and other battery sizes and types, such as, by way of non-limiting example, Lithium-Ion (Li-Ion), Nickel-Zinc (NiZn), and Nickel-Cadmium (NiCd) batteries. Non-limiting examples of possible variations of algorithm 100 are described in more detail below.

[0044] Algorithm 100 is configured to transition the charging current between various charging states of a plurality of potential charging states in response to (i.e., as determined by) the outcome of a conditional statement that uses a measured input parameter of the charging current as a condition of the conditional statement. The illustrated algorithm 100 uses charging states S0, S1, S2, S3, S4, S5, S6, S7, S8, S9, and S10. Charging state S0 may be referred to as the "initialization" or "initial" state S0, and occurs automatically when device 2 is powered on via power button 18. After initialization S0 is complete, algorithm 100 selectively transitions the charging current between various sequences of charging states S1-S8 to charge supercapacitor 72 to charging state S9 (a therapy-ready state, meaning supercapacitor 72 is ready to emit an output signal to generate electroporation pulse(s)) or to reach charging state S10, where control unit 90 determines that battery 60 does not have enough charge to charge supercapacitor 72 without dropping below the minimum operating voltage of control unit 90. At charging state S10, control unit 90 stops charging supercapacitor 72 and indicates to the user that battery 60 is generally depleted. Thus, charging state S10 can also be referred to as a "battery depleted" state and / or an "aborted" state. Charging state S10 provides an important safety feature. This is because, among other things, if the charging current causes the voltage to drop below the minimum operating voltage of control unit 90, control unit 90 will not be able to reliably monitor the input parameters while the supercapacitor is charging and, if left uninterrupted, various components may overheat and cause damage to device 2.

[0045] The algorithm 100 of the illustrated embodiment uses two general modes of active charging: (1) primary charging (states S1, S4, and S7), in which the battery 60 charges the supercapacitor 72 toward a full charge level (i.e., "full charge"); and (2) top-off charging (state S9), which occurs after the supercapacitor 72 reaches a minimum threshold charge level substantially close to its full charge level. For purposes of this disclosure, the supercapacitor 72 may be characterized as being fully charged when it is at or above the minimum threshold charge level (measured by voltage). During top-off charging (state S9), a charging current is used to maintain the supercapacitor 72 substantially full charge (i.e., at a constant voltage). In the illustrated embodiment, once the charging current enters top-off charging (state S9), the device 2 is ready for therapy. Thus, charging state S9 may be synonymously referred to as the "top-off" and "ready for therapy" charging states S9. The algorithm 100 of the illustrated embodiment also includes indicated charge states S2, S3, S5, S6, S8 that indicate to the user the transition from primary charging S1, S4, S7 to top-off charging S9. Additionally, in the indicated charge states S2, S3, S5, S6, S8, the algorithm 100 instructs the control unit 90 to indicate to the user (via the power LED 25) whether the battery 60 generally has a normal charge level or a low charge level when charging the supercapacitor 72 to full charge. In some embodiments of the algorithm 100, the indicated charge states S2, S3, S5, S6, S8 can be said to occur momentarily between primary charging S1, S4, S7 and top-off charging S9.

[0046] In the illustrated embodiment, the algorithm 100 selects between three (3) potential primary charging states S1, S4, S7 for charging the supercapacitor 72, with each primary charging state S1, S4, S7 utilizing a different maximum charging current magnitude (e.g., high, medium, and low current) and tailored to correspond to a battery charge level associated with a preselected battery type. The algorithm 100 is configured to transition between the primary charging states S1, S4, S7 from high current (S1), to medium current (S4), to low current (S7) primary charging as needed to charge the supercapacitor 72 while maintaining at least a minimum operating voltage of the control unit 90. It should be understood that the following example current magnitudes used for the primary charging states S1, S4, and S7 are based on the non-limiting implementation examples described above. Other embodiments of the algorithm 100 may use different maximum current magnitudes.

[0047] The primary charge state S1 uses a charge current of approximately 2000 milliamps (2 amps), which is the highest charge current of any primary charge state. S1 may therefore also be characterized as the "high charge" primary charge state S1. The 2000 milliamp charge current is particularly beneficial for use with power sources that can handle high current draws (e.g., charging currents), such as NiMH batteries.

[0048] The primary charge state S4 utilizes a charge current of approximately 446 milliamps (0.446 amps) and may also be referred to as a "medium charge" primary charge state S4. The approximately 446 milliamps (0.446 amps) charge current may be advantageously utilized for both NiMH and alkaline batteries 60. For example, the approximately 446 milliamps charge current may provide a stepped-down charge current (from S1) for a NiMH battery 60. Additionally, an alkaline battery 60 having a full or high battery charge level may be discharged 446 milliamps while still maintaining at least the minimum operating voltage of the control unit 90.

[0049] The primary charging state S7 utilizes a charging current of approximately two hundred fifty milliamps (0.250 amps) and may also be referred to as the "low charge" primary charging state S7. The 250 milliamp charging current is particularly useful in applications where it extracts the remaining charge available in the NiMH battery 60 and provides a stepped-down charging current (from S4) to the alkaline battery 60 while maintaining at least the minimum operating voltage of the control unit 90.

[0050] The algorithm 100 uses the following measured input parameters to determine the transition paths between the charging states S0-S10: (A) Battery voltage (“Vbatt”), i.e., the battery voltage measured at each state of charge. The battery voltage (Vbatt) is measured at a first location, which may be at the battery output terminals 62 or between the output terminals 62 and the first boost regulator 88. (B) Battery delta voltage ("Vd"), i.e., the change / drop in battery voltage when a load (i.e., supercapacitor 72) is applied to the battery 60. The change / drop in battery voltage is calculated by measuring the ongoing voltage of the battery as it charges the supercapacitor 72 and comparing the ongoing value to a baseline no-load value of the battery voltage (Vbatt). The battery delta voltage (Vd) may be measured at a first location. (C) A first boost voltage ("5V2"), i.e., the boost voltage generated by the first boost regulator 88 and measured at a second location at the first boost regulator 88 or between the first and second boost regulators 88, 86. (D) A second boosted voltage ("VDD_CAP"), i.e., the boosted voltage generated by the second boost regulator 86 and measured at a third location, either at the second boost regulator 86, at the supercapacitor 72, or at an intermediate location therebetween (in the illustrated embodiment, the second boosted voltage is the voltage going into the supercapacitor 72). (E) State charge duration (“t”), i.e., the charge duration at a particular primary charge state S1, S4, S7. (F) Total charging period (“T total”), i.e., the total primary charging period beginning at the start of the high current primary charging state S1.

[0051] It should be appreciated that by measuring these input parameters, the control unit 90 effectively determines the type of batteries 60 used within the battery housing 50 (as instructed by the algorithm 100) and their collective battery charge level.

[0052] With continued reference to FIG. 6, a further description of the algorithm 100 will be described. When the device 2 is turned on, the control unit 90 executes the algorithm 100 starting from an initial charging state S0 where no charging current is drawn from the battery 60 and the power LED 25 is in an off state. At the initialization S0, the control unit 90 starts measuring the battery voltage (Vbatt) at a first position and also measures the first boosted voltage (5V2) at a second position to determine whether the measurements are equal to or exceed respective predefined thresholds, which serve as a prerequisite for triggering a transition to S1 or S10. In particular, the control unit 90 samples the battery voltage (Vbatt) and the first boosted voltage (5V2) at a sampling interval of 100 milliseconds (ms). If the control unit 90 determines that the battery voltage (Vbatt) does not exceed (i.e., is less than) the threshold of 2.1 volts, the charging state transitions from S0 to the battery depleted state S10. In the low battery state S10, the control unit 90 causes the power LED 25 to flash red to indicate to the user that the battery 60 lacks sufficient battery charge to charge the superconductor 72. This instructs the user to either charge the battery 60 via the USB-C port 67 or replace the battery with a different NiMH or alkaline battery 60 and try again. However, if during initialization S0 the control unit 90 determines that the battery voltage (Vbatt) is above the threshold of 2.1 volts and the average of the first boost voltage (5V2) measurements is equal to or greater than the threshold of 2.5 volts, then the charging current transitions to S1 (high current primary charging).

[0053] At the start of the high current primary charge S1, the charging circuit 80 draws current from the battery and provides a 2000 milliamp charge current to the supercapacitor 72. Additionally, the control unit 90 starts measuring the state charge duration t and the total charge duration T. The control unit 90 also causes the power LED 25 to flash green to indicate to the user that the device 2 is in either the primary charge state S1, S4, or S7. The control unit 90 continues to sample the battery voltage (Vbatt) and the first boost voltage (5V2) at 100 millisecond (ms) intervals. The control unit 90 also starts measuring the battery delta voltage (Vd) and the second boost voltage (VDD_CAP), the latter measured at the third position, at the sampling interval (100 ms). Under the aforementioned conditions, if the control unit 90 determines that the second boost voltage (VDD_CAP) is greater than or equal to (i.e., reaches or achieves) a minimum threshold voltage of 11.7 volts (i.e., substantially equal to the full voltage of the supercapacitor) before the state charging period t is equal to the first threshold state charging period of 60 seconds, the charging current transitions to the indicated charging state S2 unless any of the following three trigger conditions occur before the first threshold charging period (t≦60 seconds), which are as follows: (1) the battery delta voltage (Vd) is greater than or equal to a threshold delta voltage of 0.6 volts, or (2) the battery voltage (Vbatt) is less than or equal to a threshold voltage of 1.9 volts, and (3) or the first boost voltage (5V2) is less than or equal to a threshold voltage of 2.5 volts, as further described below.

[0054] In the indicated charging state S2, the algorithm 100 instructs the control unit 90 to illuminate the power LED 25 green to indicate to the user that the supercapacitor 72 is fully charged and that the battery 60 remains at at least a moderate charge level. The power LED 25 continues to illuminate green during the top-off charging state S9. However, if the control unit 90 determines that the second boost voltage (VDD_CAP) reaches the threshold voltage of 11.7 volts at or after the first threshold state charging period (t=60 seconds), but only before the state charging period t equals the second threshold state charging duration of 90 seconds (t=90 seconds), the algorithm 100 instructs the control unit 90 to transition the charging current to the indicated charging state S3, unless any of the three trigger conditions described above occur. In S3, the power LED 25 illuminates yellow to indicate to the user that the supercapacitor 72 is fully charged, but that the battery 60 is at a low battery charge level after the supercapacitor is charged. Thereafter, the power LED 25 remains lit yellow throughout the top-off charging state S9.

[0055] Referring again to the high current primary charging state S1, if the state charging period t equals or exceeds the second threshold state charging period 90 seconds (t=90 seconds) before the second boosted voltage (VDD_CAP) can equal the threshold voltage of 11.7 volts (i.e., before supercapacitor 72 reaches full charge) and before any of the three triggering conditions occur, the control unit 90 transitions the charging current to the battery depleted state S10. However, if any of the three triggering conditions occur before the second boosted voltage (VDD_CAP) reaches the threshold voltage of 11.7 volts and before the third threshold state charging period (t=90 seconds) has elapsed, the control unit 90 transitions the charging current to the medium current primary charging state S4.

[0056] At the start of the medium current primary charging state S4, the charging current is reduced to approximately 446 milliamps and the control unit 90 begins measuring the respective state charging period t (i.e., the control unit 90 begins measuring a new state charging period t beginning at t=0). The control unit 90 continues measuring the total charging period T that began at the start of state S1. The power LED 25 continues to flash green to indicate that the device 2 remains in either of the primary charging states S1, S4, or S7. The control unit 90 may resume sampling of one or more input parameters. For example, the control unit 90 may resume sampling the battery delta voltage (Vd) and the first boost voltage (5V2) at 100 millisecond (ms) intervals while continuing to sample the second boost voltage (VDD_CAP) and the battery voltage (Vbatt). Under the aforementioned conditions, if the control unit 90 determines that the second boosted voltage (VDD_CAP) reaches the threshold voltage of 11.7 volts (i.e., supercapacitor 72 reaches full charge) before the state charging period t equals the first threshold state charging period of 90 seconds (t=90 seconds) and before the total charging period T exceeds the total charging period threshold of 150 seconds (T>150s), the charging current transitions to the indicated charging state S5 unless any of the three previously described trigger conditions previously occurred.

[0057] In charging state S5, the power LED 25 illuminates green to indicate to the user that the supercapacitor 72 is fully charged and that the battery 60 remains at at least a moderate charge level. The power LED 25 then remains green throughout the top-off charging state S9. However, if the control unit 90 determines that the second boost voltage (VDD_CAP) reaches a threshold voltage of 11.7 volts (i.e., the supercapacitor 72 reaches full charge) at or after the first threshold state charging period (t=90 seconds) but before the state charging period t equals the second threshold state charging period of 120 seconds (t=120 seconds) and before the total charging duration T exceeds a total charging period threshold of 150 seconds (T>150s), the algorithm 100 instructs the control unit 90 to transition the charging current to the indicated charging state S6, unless any of the three trigger conditions described above occur. In S6, the power LED 25 illuminates yellow to indicate to the user that the supercapacitor 72 is fully charged but the battery 60 is at a low battery charge level after charging the supercapacitor. The power LED 25 then remains yellow throughout the top-off charging state S9.

[0058] Referring again to the medium current primary charging state S4, if none of the three trigger conditions occur before the second boosted voltage (VDD_CAP) reaches the threshold voltage of 11.7 volts (i.e., the supercapacitor 72 does not reach full charge) and the state charging period t equals or exceeds the second threshold state charging period of 120 seconds (t=120 seconds), or before the total charging period T exceeds the total charging period threshold of 150 seconds (T=150 seconds), the algorithm 100 instructs the control unit 90 to transition the charging current to the battery depleted state S10. However, if any of the three trigger conditions occur before the second boosted voltage (VDD_CAP) reaches the threshold voltage of 11.7 volts (i.e., before supercapacitor 72 reaches full charge), and before the second threshold state charging period (t=120 seconds) has elapsed, and before the total charging period threshold of 150 seconds (T=150 seconds) has elapsed, algorithm 100 instructs control unit 90 to transition the charging current to low current primary charging state S7.

[0059] At the start of the low current primary charging state S7, the charging current is reduced to approximately 250 milliamps and the control unit 90 begins measuring the respective state charging period t (i.e., the control unit 90 begins measuring a new state charging period t beginning at t=0). The control unit 90 continues measuring the total charging period T that was initiated at the start of state S1. The power LED 25 continues to flash green to indicate that the device 2 remains in either the primary charging state S1, S4, or S7. The control unit 90 resumes sampling the battery delta voltage (Vd) and the first boost voltage (5V2) at 100 millisecond (ms) intervals while continuing to sample the second boost voltage (VDD_CAP) and the battery voltage (Vbatt). Under the aforementioned conditions, if the control unit 90 determines that the second boost voltage (VDD_CAP) reaches a threshold voltage of 11.7 volts (i.e., the supercapacitor 72 reaches full charge) before the charging state duration t reaches a threshold voltage of 140 seconds (t=140 seconds) and before the total charging period T exceeds a threshold voltage of 150 seconds (T=150 seconds), the algorithm 100 instructs the control unit 90 to transition the charging current to an indicated charging state S8, unless either of the following two triggering conditions occurs previously: (1) the battery voltage (Vbatt) is equal to or less than a threshold voltage of 1.6 volts; or (2) the first boost voltage (5V2) is equal to or less than a threshold voltage of 2.5 volts. In the indicated charging state S8, the power LED 25 is illuminated yellow to indicate to the user that the supercapacitor 72 is fully charged, but the battery 60 is at a low battery charge level after charging the supercapacitor. The power LED 25 then remains illuminated yellow throughout the top-off charging state S9. However, if either of the two previously discussed trigger conditions occurs in the low current primary charging state S7, the algorithm 100 instructs the control unit 90 to transition the charging current to the battery depleted state S10. For the low current primary charging state S7, the battery voltage (Vbatt) threshold of 1.6 volts in the illustrated embodiment was selected because it provides a safety margin above the 0.5 volts that represents the minimum battery voltage required for all electrical components of the device 2 to operate as intended.A battery voltage of 1.6 volts (Vbatt) while under load (i.e., while charging supercapacitor 72) provides enough margin to cause power LED 25 to flash red, thereby indicating that battery 60 is depleted and needs to be recharged or replaced. It should be appreciated that by transitioning the charging current to a lower current charging state when various thresholds are triggered, algorithm 100 also effectively provides safety protection that prevents, or at least significantly reduces the likelihood of, battery overload and potential overheating that could otherwise result in negative consequences, particularly if an overheated battery produces inefficient or insufficient power output, or even worse, damage, corrosion, fire, and / or other issues to device 2.

[0060] In the top-off charging state S9, the algorithm 100 instructs the control unit 90 to send a charging current at about 250 milliamps to the supercapacitor 72. In the illustrated embodiment, a top-off charging current of about 250 milliamps was selected for a number of reasons, including simplicity, considering that in the illustrated example, 250 milliamps is also the charging current used during the primary charging state S7. The algorithm 100 can instruct the control unit 90 to use the top-off charging current (about 250 milliamps) to maintain the supercapacitor 72 at a fully charged level, which in the illustrated example is between a minimum threshold of 11.7 volts and an upper voltage limit setting of 11.84 volts. It should be appreciated that while the supercapacitor 72 in the illustrated embodiment has a maximum (fully charged) voltage of 12.0 volts, the algorithm 100 imposes an upper voltage limit of 11.84 volts during the top-off charging S9 to extend the useful life of the supercapacitor 72. It should be appreciated that the magnitude of the top-off charge current can be adjusted as needed based on the particular implementation. It should also be appreciated that in the illustrated example, after supercapacitor 72 reaches full charge, if no load is applied to it, supercapacitor 72 draws significantly less than 250 milliamps of current to maintain a full charge.

[0061] Also, in the top-off charging state S9, the algorithm 100 instructs the control unit 90 to keep the power LED 25 in the same indication from the respective indicating charging state S2, S3, S5, S6, or S8 to which the charging signal has transitioned. Thus, if the charging current transitions to the top-off charging state S9 from S2 or S5, the power LED 25 will illuminate green throughout the top-off charging, but if the charging current transitions to the top-off charging state S9 from S3, S6, or S8, the power LED 25 will illuminate yellow throughout the top-off charging. Furthermore, in the top-off charging state S9, the algorithm 100 instructs the control unit 90 to illuminate the treatment LED 26 green, which indicates that the device 2 is ready for treatment, i.e., when the user activates the delivery trigger 20, the supercapacitor 72 is ready to release an output signal to the downstream components, which convert the output signal into one or more electroporation pulses. After the supercapacitor 72 releases the output signal, the algorithm 100 instructs the control unit 90 to terminate charging of the supercapacitor. As a non-limiting example, the control unit 90 terminates charging of the supercapacitor after one or more impedance test pulses have been delivered to the tissue with successful results, but before the first electroporation pulse of the sequence is delivered to the tissue. Preferably, after the output signal is released, the algorithm 100 instructs the control unit 90 to turn off the device 2, so that the device 2 remains off until the user presses the power button 18 to turn the device 2 on and resume the charging sequence. This serves as a disposable safety feature of the device 2.

[0062] It should be understood that the aforementioned high, medium, and low charging currents (i.e., about 2000 mA, about 446 mA, and about 250 mA, respectively) were selected for a specific, non-limiting example of the algorithm 100 for the illustrated embodiment, and that these current values ​​were selected for specific purposes and considerations related to optimizing user interface parameters (e.g., power LED and therapy LED) and battery capacity. It should also be understood that the aforementioned input parameters (e.g., battery voltage (Vbatt), battery delta voltage (Vd), first boost voltage (5V2), second boost voltage (VDD_CAP), state charge period (t), and total charge period (T)) and their respective thresholds were selected based on specific purposes and considerations related to the illustrated embodiment. Non-limiting examples of such purposes and considerations are described below.

[0063] S1, High Current (2000mA) Primary Charge: The primary charge state S1 is intended for power sources that can handle high current drain, such as NiMH batteries or alkaline batteries with high battery charge levels. A charge current of 2000 milliamps was selected as the maximum current to use for the illustrated embodiment. This current level is intended for use with NiMH batteries. NiMH batteries can withstand a supercapacitor drain level of 2000 milliamps that charges most of the battery capacity (approximately 64%). If the battery voltage (Vbatt) during this high charge current drops too low or the battery delta voltage (Vd) rises too high, the action of transitioning to S4 and potentially to S7 allows the charging circuit 80 to utilize the remaining (approximately 36%) charge. The 2000 milliamp charge current is also useful for alkaline batteries with high battery charge levels, but even fully charged alkaline batteries tend to trigger a transition to the primary charge state S4 after approximately 4-6 uses.

[0064] It should be appreciated that as the battery depletes during S1 charging and the battery voltage essentially drops, the current drawn from the battery 60 must be increased to maintain the power required by the first boost regulator 88 (5V2) for the high current charge S1. If this power is too great to drain the battery without collapsing the first boost regulator output (5V2), the charging of the supercapacitor stops (i.e., the charging current transitions to S10). However, if the battery voltage (Vbatt), battery delta voltage (Vd), and first boost voltage (5V2) are within their thresholds, the high current primary charge S1 continues until the supercapacitor reaches a full charge voltage level (at least 11.70 volts) or the state charge period (t) exceeds its threshold. Through testing, the inventors have determined that it takes an average of about 21 seconds to charge a supercapacitor with a high current charge S1 using a NiMH battery.

[0065] S4, medium current (446 mA) primary charge: The primary charge state S4 uses a lower charge current than S1 and is intended for use with both NiMH and alkaline batteries. The 446 milliamp charge level was selected for S4 in the illustrated embodiment because it is an appropriate step-down current for NiMH batteries (e.g., to drain the remaining 30% of capacity before a lower charge current is required) and because alkaline batteries can handle the required power output so that the first boost regulator (5V2) does not collapse. Through testing, the inventors have determined that it takes an average of about 45 seconds (total) to charge the supercapacitor 72 (combining both NiMH and alkaline batteries) when a transition from S1 to S4 is involved, with individual charge periods ranging from about 30 seconds to about 140 seconds when S4 is used at any point in the charging process.

[0066] S7, low current (250mA) primary charge: The primary state of charge S7 is the lowest charge current used in the illustrated embodiment if any of the battery voltage (Vbatt), battery delta voltage (Vd), or first boost voltage (5V2) exceed their thresholds during S4. In the illustrated embodiment, a charge level of 250 milliamps was selected for S7 because it further reduces the charging load, allows the NiMH battery to utilize the last remaining remainder of its charge, and allows the alkaline battery to have a secondary primary charge level to operate. For example, it has been observed through testing that applying a charge current of 250 milliamps in the primary state of charge S7 helps to efficiently extract approximately 50-60% of the remaining battery charge from an AA-size alkaline battery. It should be understood that in the illustrated embodiment, alkaline batteries are expected to operate primarily in the medium and low current primary states of charge S4, S7 because the characteristics of alkaline batteries are more suited to longer durations of medium and / or low current drain. Through testing, the inventors have determined that when transitions from S1 to S4 and S4 to S7 are involved (combined for both NiMH and alkaline batteries), it takes an average of about 90 seconds (total) to charge supercapacitor 72, with individual charging periods ranging from about 60 seconds to about 140 seconds when using S7 at any point in the charging process.

[0067] Transitions between charging states: The electronic hardware (e.g., charging circuit 80 and other device circuits) is designed to monitor various critical components and use those measurements to help optimize the supercapacitor charging cycle. In the illustrated embodiment, the battery voltage (Vbatt) and battery delta voltage (Vd) are monitored only during initialization S0 and primary charging states S1, S4, and S7. And the first boost voltage ("5V2") and second boost voltage ("VDD_CAP") are monitored throughout top-off charging S9 and beyond. The power supply voltages (i.e., battery voltage (Vbatt) and battery delta voltage (Vd)) and the first and second boost regulator voltages (5V2 and VDD_CAP) are actively monitored along with the status and total charging period (t and T) to determine the battery type (i.e., NiMH or alkaline) and its charge level until the supercapacitor charging cycle is completed. These parameters are measured and used to determine, among other things, the appropriate charging current to use for the battery type and battery charge level.

[0068] Battery Delta Voltage(Vd): In the illustrated embodiment, the battery delta voltage (Vd) is measured only at the high and medium current primary charging states S1, S4. Preferably, the battery delta voltage (Vd) is monitored for a short period of time (100 millisecond intervals totaling 1.6 seconds) as charging begins at each of S1 and S4. A baseline voltage of the battery is recorded at initialization and used to compare with the active battery voltage (Vbatt) measurement to calculate the battery delta voltage (Vd) during the primary charging states S1 and S4. This battery delta voltage (Vd) reading can be used to effectively determine how much charge remains in the battery. As the battery charge level decreases, the battery delta voltage (Vd) increases with each load (e.g., S1 and S4). At a certain threshold, the battery delta voltage (Vd) may indicate that the battery cannot sustain the charging load and therefore a transition to a lower current charging state (e.g., S1 to S4, and potentially S4 to S7) is required. In the illustrated embodiment, a battery delta voltage (Vd) threshold of 0.6 volts was selected. This is because it represents a response from the battery indicating that it cannot sustain the applied load without collapsing the first boosted voltage (5V2), and therefore the algorithm 100 instructs the control unit 90 to transition to the lower primary charge state S4 or S7 before the 5V2 collapse event occurs.

[0069] Battery voltage(Vbatt): The battery voltage (Vbatt) is monitored throughout each of the primary charging states S1, S4, S7 during initialization S0 and stops as soon as the supercapacitor reaches full charge. In each of these states, the control unit 90 samples the battery voltage (Vbatt) every 100 milliseconds. During initialization S0, the only load powered by the charging current is the control unit boost regulator 89 (3.3 volts), and if the battery voltage (Vbatt) is measured below the initial threshold (2.1 volts), the charging current transitions directly to the battery depleted state S10. If during initialization S0 the battery voltage (Vbatt) remains above the initial threshold (2.1 volts) and the first boost voltage (5V2) is measured above its respective threshold (2.5 volts), the charging current transitions to the high current primary charging state S1 where charging of the supercapacitor begins and sampling of S1 begins. If the battery voltage (Vbatt) falls below its respective threshold (1.9 volts) during S1, the charging current transitions to S4. If the battery voltage (Vbatt) falls below its respective threshold (1.9 volts) during S4, the charging current transitions to S7. If the battery voltage (Vbatt) falls below its respective threshold (1.6 volts) during S7, the charging current transitions to S10.

[0070] The main reason that the battery voltage (Vbatt) is monitored during charging states S0, S1, S4, and S7 and used to trigger state transitions is to act as a safety measure to prevent collapse of the boost voltage (3.3 volts) for operating the control unit 90 during initialization and primary charging. Relatedly, monitoring the battery voltage (Vbatt) during charging states S0, S1, S4, and S7 also facilitates transitioning to more conservative charging characteristics (e.g., lower charging current) for battery types that are less suited to high discharge. For example, when using alkaline batteries, the battery voltage (Vbatt) at S1 will immediately measure a threshold below 1.9 volts, immediately transitioning the charging current to S4, which is more suitable for alkaline batteries. In other words, using the battery voltage Vbatt as a transition parameter helps transition certain battery types to more appropriate charging currents (S4, S7) to make the most of the remaining battery capacity.

[0071] In the illustrated embodiment, 2.1 volts was selected as the threshold battery voltage (Vbatt) during initialization S0 in part because it was found to be sufficient to prevent the boost voltage (3.3 volts) from collapsing to operate the control unit 90. 1.9 volts was selected as the threshold battery voltage (Vbatt) during S1 and S4 in part because 1.9 volts is higher than the battery voltage (approximately 1.7 volts) at which the collapse of the first boost voltage (5V2) was observed. Thus, using 1.9 volts as the threshold battery voltage (Vbatt) during S1 and S4 triggers a charge state transition before the collapse event of the first boost voltage (5V2) occurs. 1.6 volts was selected as the threshold battery voltage (Vbatt) during S7 in part because 1.6 volts is higher than the minimum input voltage (approximately 0.5 volts) required to operate all electrical hardware of the device 2 as intended. Thus, employing 1.6 volts as the threshold battery voltage (Vbatt) during S7 provides sufficient margin to indicate to the user via power LED 25 that the battery is depleted and needs to be replaced or recharged (e.g., via USB-C port 67).

[0072] First boost voltage (5V2): The first boost voltage (5V2) is the output of the first boost regulator 88 and separates the second boost regulator 86 stage which boosts the battery voltage and generates the final voltage used to charge the supercapacitor 72. When the battery loses charge, the power output capability is generally reduced. A reduction in the input power at the first boost regulator 88 can cause its output to collapse below 2.0 volts. The first boost voltage (5V2) is monitored during initialization S0, throughout each primary charge state S1, S4, S7, and throughout top-off charge S9, and is stopped after the supercapacitor reaches full charge (e.g., after one or more impedance test pulses are delivered to the tissue via the electrode(s) 10). In the illustrated example, in each of these states S0, S1, S4, S7, the first boost voltage (5V2) is sampled at 100 millisecond intervals for at least 2.0 seconds (at least 20 samples), and the samples are continuously averaged thereafter. Thus, in the illustrated embodiment, the first boosted voltage (5V2) measurement is an average based on at least 20 samples, and then continuously measured for ongoing comparison to the voltage threshold (2.5V). After each state change between S0, S1, S4, and S7, the first boosted voltage (5V2) sample is reset and a new sample period begins until the next state change.

[0073] The first boost voltage (5V2) has a minimum voltage threshold of 2.5 volts and was selected primarily as a safety feature to identify the occurrence of voltage collapse required for charging the supercapacitor. In particular, this safety feature provides a backup trigger condition for state transitions so that if the first boost voltage (5V2) collapses below the threshold (2.5 volts), even if the battery delta voltage (Vd) and battery voltage (Vbatt) are adequate, the charging current transitions to a lower charging state. In particular, during initialization S0, if the first boost voltage (5V2) is measured to be below the threshold (2.5 volts), the algorithm 100 instructs the control unit 90 to indicate a device error to the user. If, while in S1, the first boost voltage (5V2) is measured to be below the threshold (2.5 volts), the charging current transitions to S4. If, while in S4, the first boost voltage (5V2) is measured to be below the threshold (2.5 volts), the charging current transitions to S7. If in S7 the first boost voltage (5V2) is measured to be equal to or less than the threshold (2.5 volts), the charging current transitions to the battery depleted state S10. In the illustrated embodiment, 2.5 volts was selected as the threshold for the first boost voltage (5V2) because it provides a safety margin above the voltage at which the first boost regulator 88 collapses (approximately 1.7 volts), while being low enough to avoid false triggers due to noise or momentary dips in the 5V2 voltage output. It is also high enough to reliably trigger a state change even if the 5V2 output collapses. It has been observed that the first boost voltage (5V2) remains stable at 5.2 volts when operating as intended, but drops to approximately 1.7 volts when the voltage collapses, so the 2.5V threshold provides enough margin to trigger a state transition before collapse.

[0074] It should also be understood that various features of algorithm 100 may be adjusted or modified while remaining within the scope of the present disclosure. For example, each of the high charge (2000 milliamps), medium charge (446 milliamps), and low charge (250 milliamps) currents may be adjusted by one or more, or up to a higher or lower current magnitude, respectively, to adjust for each primary state of charge(s) based on various factors. For example, such factors may include the use of a different battery configuration than AA-size NiMH or alkaline batteries. Additionally or alternatively, one or more, or up to all, of the thresholds for battery voltage (Vbatt), battery delta voltage (Vd), first boost voltage (5V2), second boost voltage (VDD_CAP), state charge duration (t), and total charge duration (T) may be adjusted based on various factors. Furthermore, in other embodiments, algorithm 100 need not use exactly three (3) primary states of charge, as desired. For example, algorithm 100 may optionally employ one (1), two (2), four (4), five (5), or more than five primary states of charge, each having a preselected charging current. Additionally or alternatively, various features associated with measurement sampling, such as sample amount, sampling interval, timing of sampling initiation, etc., may be adjusted as desired.

[0075] 7, in an additional embodiment, an exemplary electroporation system 200 can include a handheld electroporation device 202 and a base station 204 configured to dock with the handheld electroporation device 202. In such an embodiment, one or more components of the power supply unit 12 described above can be housed within the base station 204. For example, in the illustrated embodiment of the electroporation system 200, the base station 204 can house the battery unit 50, the battery 60, the first and second boost regulators 88, 86, the current regulator 84, and the control unit boost regulator 89. In such an embodiment, the second boost regulator 86 can transmit a charging current to the supercapacitor 72 of the docked handset 202 via a charging port, such as the USB-C port 67 described above, or a high current DC contact, and / or any electrical connection means capable of handling the required energy transfer without degradation, as non-limiting examples. Furthermore, in such an embodiment, the battery unit 50 of the base station 204 can be configured to hold additional batteries (e.g., three or more batteries 60) and / or more types of batteries, which, among other things, can provide additional battery capacity and allow for the use of higher charging currents to charge the energy storage units 70 (e.g., supercapacitors 72). Furthermore, in addition to housing batteries, the base station 204 may be connectable to an external power adapter (e.g., for connection to a wall outlet or other power source). These features may further reduce the time required to charge the energy storage units 70, allowing more patients to be treated before recharging is required. Furthermore, by locating the components of the charging circuitry 80 within the base station 204, the handheld electroporation device 202 may be made smaller and lighter, thereby increasing ease of use.It should be appreciated that many other advantages may be provided by using base station 204 to house various components of charging circuitry 80 and / or for additional battery capacity. It should also be appreciated that in other embodiments, various components of power supply unit 12 may be located within handheld electroporation device 2, while other components are located within base station 204.

[0076] It should further be appreciated that in embodiments using a base station 204, various design modifications can be used to ensure that the control unit 90 has sufficient power to control the operation of the handheld device 202. For example, one or more additional energy storage devices, such as one or more additional supercapacitor(s), capacitor(s), and / or battery(s), can be disposed within the handheld device 202 to power the control unit 90 and can be charged by the base station 204. Moreover, it should be appreciated that still other modifications can be made to the configuration of the base station 204 and associated handheld device 202 while remaining within the scope of the present disclosure.

[0077] It should be understood that the various features of the devices, systems, methods, and algorithms described above are provided as exemplary features for adapting a handheld electroporation device to more efficiently charge and store power for delivering electroporation pulses. These parameters can be adjusted as needed without departing from the scope of the present disclosure.

[0078] Furthermore, when a numerical preposition (e.g., "first," "second," "third") is used herein in reference to an element, component, dimension, process step, or feature thereof, it is to be understood that such numerical preposition is intended to distinguish said element, component, dimension, and / or feature from another such element, component, dimension, process step, and / or feature, and is not limited to the particular numerical preposition used in that instance. For example, a "first" component may also be referred to as a "second" component in a different context without departing from the scope of the present disclosure, so long as, in the context in which the numerical preposition is used, said component (and / or element, dimension, process step, and / or feature) is appropriately distinguished.

[0079] Although the present disclosure has been described in detail, it should be understood that various changes, substitutions, and alterations can be made herein without departing from the spirit and scope of the present invention as defined by the appended claims. Moreover, the scope of the present disclosure is not intended to be limited to the specific embodiments described in the specification. In particular, one or more features of the above-described embodiments can be used in other embodiments herein. Those skilled in the art will readily appreciate that any now existing or later developed process, machine, manufacture, composition of matter, means, methods, or steps that perform substantially the same function or achieve substantially the same result as the corresponding embodiments described herein can be utilized in accordance with the present disclosure.

Claims

1. 1. A method of preparing an electroporation device for administering electroporation therapy, comprising: providing a charging current from at least one battery to the supercapacitor unit via a charging circuit; Charging the supercapacitor unit with the charging current, the charging step comprising: measuring one or more input parameters of the charging current while the charging current is in at least one of a plurality of charging states for charging the supercapacitor unit; and at least one step of transitioning the charging current between charging states of the plurality of charging states in response to the one or more measured input parameters, the step of transitioning the charging current comprising adjusting a magnitude of the charging current; A method wherein the measuring and transitioning steps are automatically controlled by a control unit executing machine-readable instructions.

2. the at least one battery is selected from the group including alkaline batteries, NiMH batteries, and Li-Ion batteries; More preferably, the at least one battery comprises a pair of batteries selected from the group consisting of alkaline batteries and NiMH batteries. The method of claim 1.

3. the one or more input parameters are selected from the group including a battery voltage measured at a first location, a change in the battery voltage when a charging load is applied to the at least one battery, a first boosted voltage measured at a second location between the at least one battery and the supercapacitor unit, a second boosted voltage measured at a third location between the second location and the supercapacitor unit, and a charging duration; The method of claim 1 , further comprising determining whether the one or more measured input parameters satisfy a condition statement for triggering the at least one transition step.

4. the plurality of states of charge include a set of primary states of charge; The set of primary states of charge is: a first primary state of charge in which the current is substantially maintained at a first current value; a second primary state of charge in which the current is substantially maintained at a second current value less than the first current value; 4. The method of claim 3, wherein when the transitioning steps include transitioning the charging current from one charge state to another charge state that are both in the set of primary charge states, the adjusting step includes decreasing the current.

5. 5. The method of claim 4, wherein the at least one transitioning step includes transitioning the charging current from the first primary charging state to the second primary charging state, thereby regulating the current from the first current value to the second current value.

6. 6. The method of claim 5, wherein the first current value is in a range of about 1000 milliamps to about 3000 milliamps, and the second current value is in a range of about 300 milliamps to about 600 milliamps.

7. 5. The method of claim 4, further comprising the step of boosting a voltage of the charging current from the battery voltage to the first boost voltage, the boosting step being performed by a first boost regulator of the charging circuit, the first boost regulator being located at a second location or upstream of a second location.

8. 8. The method of claim 7, further comprising the step of further boosting the voltage of the charging current from the first boost voltage to the second boost voltage, the further boost step being performed by a second boost regulator of the charging circuit, the second boost regulator being positioned either in the third position or intermediate between the second position and the third position.

9. 9. The method of claim 8, wherein the battery voltage is in the range of about 0.5 volts to about 3.0 volts, the first boosted voltage is in the range of about 3.0 volts to about 7.0 volts, and the second boosted voltage is in the range of about 7.0 volts to about 20 volts.

10. The measuring step sampling the battery voltage at the first location at a sampling interval; and sampling the first boosted voltage at the second location during the sampling interval.

11. The method of claim 10, wherein the sampling interval is in the range of about 0.1 milliseconds to about 1.0 seconds.

12. the control unit obtains measured battery voltage samples and measured first and second boosted voltage samples and calculates an average value of the first boosted voltage; The method of claim 10 , wherein the one or more input parameters include the average values ​​of the battery voltage and the first boost voltage.

13. 5. The method of claim 4, wherein the at least one transitioning step includes transitioning the charging current from one of the primary charge states to a top-off charge state after the supercapacitor unit reaches a full charge level.

14. concurrently with transitioning the charging current to the top-off charging state, the device further includes communicating an indication that the device is ready to treat; 14. The method of claim 13, wherein the supercapacitor unit has a voltage in the range of about 11.5 volts to about 12.5 volts when at the fully charged level.

15. the plurality of charge states include an initial charge state in which the one or more measured input parameters include the battery voltage and no charging current is supplied to the supercapacitor unit; the at least one transition step includes transitioning the charging current from the initial charging state to the first primary charging state; the adjusting step includes adjusting the charging current from an initial current value of substantially zero to the first current value; The method of claim 4 , further comprising, prior to said at least one transitioning step, determining whether said measured battery voltage is greater than or equal to a threshold voltage value.

16. In each of the primary states of charge, (1) until the supercapacitor unit reaches a full charge level or (2) the charging period exceeds a respective time limit associated with each primary charge state.

7. The method of claim 6, wherein the respective current values ​​are maintained for at least a respective predetermined period unless at least one of the one or more input parameters meets a threshold limit that triggers a transition to a discontinued state of the plurality of charging states before the supercapacitor unit reaches the full charge level or the charging period exceeds a respective period limit.

17. the at least one transitioning step includes (1) transitioning the charging current from one of the first and second primary charging states to the suspended state in response to the charging duration exceeding the respective duration limit, or (2) the control unit determining that the at least one of the one or more input parameters meets the threshold limit; The method of claim 16 , wherein the adjusting step includes adjusting the respective current values ​​to substantially zero.

18. the set of primary states of charge further includes a third primary state of charge in which the magnitude of the charging current is substantially maintained at a third current value that is less than the second current value; The method of claim 4, wherein the third current value is in the range of about 150 milliamps to about 300 milliamps.

19. The at least one transition step comprises: transitioning the charging current from the second primary charging state to the third primary charging state, thereby adjusting the magnitude of the charging current from the second current value to the third current value; transitioning the charging current from the third primary charging state to a top-off charging state after the supercapacitor unit reaches a full charge level; 20. The method of claim 18, further comprising:

20. the one or more input parameters include a charging duration; The method comprises: maintaining the current at the third current value for at least a predetermined duration until (1) the supercapacitor unit reaches a fully charged level or (2) the charging period exceeds a duration limit associated with the third primary state of charge; determining that the charging period has exceeded the period limit; 20. The method of claim 18, further comprising: in response thereto, transitioning the charging current to a discontinued state of the plurality of charging states, thereby adjusting the current from the third current value to substantially zero.

21. further comprising the step of communicating indicator signals to a user, each of said indicator signals indicating a transition between charging states; the step of communicating an indication signal includes communicating an optical indication signal to at least one LED display, and further optionally communicating at least one audible indication signal to a speaker carried by the electroporation device. The method of claim 1.

22. A power supply unit for an electroporation apparatus, comprising: a battery unit configured to interchangeably connect to a first type of battery and a second type of battery; an energy storage unit configured to be interchangeably charged by the first type battery and the second type battery, the energy storage unit further configured to release a total energy of at least about 30 joules; an integrated circuit configured to execute computer-readable instructions; A charging circuit in electrical communication with the battery unit and the energy storage unit, the charging circuit operable under control of the integrated circuit to: configured to measure one or more input parameters of a charging current drawn from the battery unit; a charging circuit further configured to adjust a magnitude of the charging current in response to the measured one or more input parameters while charging the energy storage unit with the charging current.

23. 23. The power supply unit of claim 22, wherein the first and second types of batteries are selected from the group including alkaline, NiMH, and lithium ion.

24. the first type of battery is alkaline and the second type of battery is NiMH; The battery unit is configured to interchangeably connect a pair of the first type batteries and a pair of the second type batteries, and each pair of batteries is connected in series; the integrated circuit is configured to estimate an initial charge level of each first type battery or second type battery connected to the battery unit, and the integrated circuit is further configured to reduce the magnitude of the charging current in response to the estimated initial charge level.

24. The power supply unit of claim 23.

25. 23. The power supply unit of claim 22, wherein the energy storage unit comprises a plurality of supercapacitors connected in series.

26. 23. The power supply unit of claim 22, wherein the charging circuit includes at least one sample location at which at least one of the one or more input parameters is measured, the at least one sample location being in electronic communication with the integrated circuit.

27. 27. The power supply unit of claim 26, wherein the charging circuit comprises at least one boost regulator between the battery unit and the energy storage unit, the at least one boost regulator configured to boost a voltage of the charging current to a boosted voltage.

28. The at least one boost regulator a first boost regulator in a first position within the charging circuit, the first boost regulator configured to boost a voltage of the charging current from an initial battery voltage to a first boost voltage; 28. The power supply unit of claim 27, comprising: a second boost regulator in a second location in the charging circuit, the second location being between the first location and the energy storage unit, the second boost regulator configured to boost a voltage of the charging current from the first boosted voltage to a second boosted voltage, the second boosted voltage being substantially equal to a charging voltage to which the energy storage unit is charged.

29. the first boosted voltage is in the range of about 2.0 volts to about 10.0 volts, and the second boosted voltage is in the range of about 5.0 volts to about 20 volts; The charging circuit a first sample location between the battery unit and the first boost regulator, the initial battery voltage being measured at the first sample location; a second sample location between the first boost regulator and the second boost regulator, where the first boost voltage is measured at the second sample location; 30. The power supply unit of claim 28, wherein the first and second sample locations are in electronic communication with the integrated circuit.

30. the power supply unit is insertable into a device housing of the electroporation device; 23. The power supply unit of claim 22, wherein the battery unit comprises a battery housing at least partially insertable into the device housing, the battery housing having at least one battery receptacle configured to interchangeably receive the first type of battery and the second type of battery.

31. 31. The power supply unit of claim 30, wherein the at least one battery receptacle comprises a first battery receptacle and a second battery receptacle, the first battery receptacle and the second battery receptacle each configured to interchangeably receive a pair of the first type batteries and a pair of the second type batteries.

32. further comprising at least one indicator device for indicating a state of charge of the energy storage unit; the at least one indicator device comprises an LED display for communicating one or more light signals regarding the charge state of the energy storage unit, the LED display being receivable within an opening in the device housing; 31. The power supply unit of claim 30, wherein the at least one indicator device comprises a second LED display for communicating one or more light signals indicating when the energy storage unit is fully charged.

33. the charging circuitry is disposed on a circuit board insertable into the device housing; 31. The power supply unit of claim 30, wherein the energy storage unit is mountable to the circuit board, the battery housing is connectable to the circuit board, and the battery housing has at least one electrical contact connectable with at least one electrical contact of the circuit board to provide electronic communication between the battery unit and the charging circuit.

34. the battery housing includes an electronic communication port for receiving an electronic communication device; 31. The power supply unit of claim 30, wherein the battery housing carries an LED display that indicates when the electronic communication port is connected to a cable.

35. the energy storage unit is configured to emit a total energy of approximately 90 joules; 23. The power supply unit of claim 22, wherein the energy storage unit is configured to emit discrete portions of the total energy, the discrete portions being convertible into one or more electroporation pulses.

36. A handheld electroporation device comprising: a device housing; at least one electrode connectable to the device housing; a battery unit at least partially insertable into the device housing, the battery unit configured to interchangeably connect to a first type of battery and a second type of battery; a supercapacitor unit configured to be interchangeably charged by the first type battery and the second type battery, the supercapacitor unit further configured to deliver a total energy of at least about 30 joules; a charging circuit in electrical communication with the battery unit and the supercapacitor unit, configured to provide a charging current from the battery unit to the supercapacitor unit to charge the supercapacitor unit; a charging circuit configured, under the control of an integrated circuit configured to execute machine-readable instructions, to measure at least one voltage parameter of the respective first type battery or second type battery and to adjust the magnitude of a charging current in response thereto, thereby reducing the rate at which the respective first type battery or second type battery loses charge during charging of the supercapacitor unit;

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