Self-powered pulse generator

Abstract

A device including a housing, the housing including a pulse generator disposed within the housing, a first electrode and a second electrode electrically coupled to the pulse generator, and an actuator coupled to the housing, the actuator configured to apply a mechanical force on the pulse generator, wherein the pulse generator is configured to convert the mechanical force into one or more electric pulses.

Description

[0001] 072396.1110

[0002] PATENT

[0003] SELF-POWERED PULSE GENERATOR

[0004] CROSS-REFERENCE TO RELATED APPLICATIONS

[0005] This application claims the benefit of priority of U.S. Provisional Patent Application No. 63 / 725,778, filed November 27, 2024, the content of which is incorporated herein by reference in its entirety, and to which priority is claimed.

[0006] BACKGROUND OF THE DISCLOSED SUBJECT MATTER

[0007] FIELD OF THE DISCLOSED SUBJECT MATTER

[0008] The disclosed subject matter relates to a self-powered pulse generator, and more particularly to a self-powered, lightweight high-voltage pulse generator.

[0009] DESCRIPTION OF THE RELATED ART

[0010] A variety of pulse generating systems exist for generating electrical power that can be delivered through pathways, such as electrical leads. Many such systems require external power sources to generate larger voltages. However, external power sources like batteries increase the overall weight of a portable generator system, whereas generator systems that incorporate hardwire connections to external power supplies limit the portability of the device. Other generator systems generate electric pulses with large pulse widths that can be dangerous when in contact with the skin or tissue of a user or patient.

[0011] There thus remains a continued need for an efficient and economic system for a lightweight, self-powered pulse generator capable of producing large voltages with small pulse widths. The presently disclosed subject matter satisfies these and other needs.

[0012] 514467368.1 -1- 072396.1110

[0013] PATENT

[0014] SUMMARY OF THE DISCLOSED SUBJECT MATTER

[0015] The purpose and advantages of the disclosed subject matter will be set forth in and are apparent from the description that follows, as well as will be learned by practice of the disclosed subject matter. Additional advantages of the disclosed subject matter will be realized and attained by the devices particularly pointed out in the written description and claims hereof, as well as from the appended drawings.

[0016] To achieve these and other advantages and in accordance with the purpose of the disclosed subject matter, as embodied and broadly described, the disclosed subject matter includes a device including a housing, the housing including a pulse generator disposed within the housing, a first electrode and a second electrode electrically coupled to the pulse generator, and an actuator coupled to the housing, the actuator configured to apply a mechanical force on the pulse generator, wherein the pulse generator is configured to convert the mechanical force into one or more electric pulses.

[0017] According to embodiments of the disclosed subject matter, the pulse generator is configured to produce one or more electric pulses with a peak voltage between 1 V and 50,000 V. According to embodiments of the disclosed subject matter, the one or more electric pulse has a pulse length between 1 nanosecond and 10 milliseconds. According to embodiments of the disclosed subject matter, the pulse generator comprises a piezo crystal, a spring-latch hammer, and electrical connections, wherein the piezo crystal comprises at least one of lead zirconate titanate (PZT), Barium Titanate (BT), quartz, and zinc oxide.

[0018] According to the disclosed subject matter, the device can further include a chip coupled to the housing, the chip including a top surface and a bottom surface, the top surface having a reservoir containing a drug therein and the bottom surface having at least one of hollow

[0019] 514467368.1 -2- 072396.1110

[0020] PATENT microchannels and hollow microneedles extending from the bottom surface, and wherein the first electrode is configured to be disposed in contact with the reservoir, wherein the second electrode is configured to be disposed in or on a target tissue or skin, and wherein the one or more electric pulses generated by the pulse generator are configured to drive delivery of the drug from the reservoir to the target tissue or skin. In embodiments, the reservoir is plastic. In some embodiments, the drug is at least one of charged biomolecules, DNA, and RNA. According to embodiments of the disclosed subject matter, the housing can include springs for releasably coupling to the chip. In accordance with the disclosed subject, a second chip is provided, the second chip couplable to the housing.

[0021] According to embodiments described herein, described is a system including a first module including a device including a housing, the housing including a pulse generator disposed within the housing, a first electrode and a second electrode electrically coupled to the pulse generator, and an actuator coupled to the housing, the actuator configured to apply a mechanical force on the pulse generator, wherein the pulse generator is configured to convert the mechanical force into one or more electric pulses, and a chip coupled to the housing, the chip including a top surface and a bottom surface, the top surface having a reservoir containing a drug therein and the bottom surface having at least one of hollow microchannels and hollow microneedles extending from the bottom surface, and wherein the first electrode is configured to be disposed in contact with the reservoir, wherein the second electrode is configured to be disposed in or on a target tissue or skin, and wherein the one or more electric pulses generated by the pulse generator are configured to drive delivery of the drug from the reservoir to the target tissue or skin. The system can include a second module including at least one of a heating device and an ultrasound generating device. According to embodiment of the disclosed subject matter, the heating device is configured to directly contact the target or skin and / or the

[0022] 514467368.1 -3- 072396.1110

[0023] PATENT ultrasound generating device is configured to administer acoustic waves to the target tissue or skin and / or the second module comprises an opening configured to surround a bottom surface of the first module, and wherein the first module and the second module are configured to contact the target tissue or skin simultaneously. In some embodiments, the second module includes both the heating device and the ultrasound generating device. According to embodiments of the disclosed subject matter, the second module includes an external power source.

[0024] In accordance with another aspect of the disclosed subject matter, a method of drug delivery includes contacting a target tissue or skin with a device, the device including: a pulse generator disposed within the housing, an actuator coupled to the housing, the actuator configured to apply a mechanical force on the pulse generator a first electrode and a second electrode electrically coupled to the pulse generator, and a chip configured to be releasably coupled to the housing, the chip including a top surface and a bottom surface, the top surface having a reservoir comprising a drug and the bottom surface having at least one of hollow microchannels and hollow microneedles extending from the bottom surface, wherein the first electrode is configured to be disposed in contact with the reservoir, wherein the second electrode is configured to be disposed in or on a target tissue or skin, and wherein the pulse generator is configured to convert the mechanical force to produce one or more electric pulses, activating the pulse generator using the actuator; and delivering the drug from the reservoir to the target tissue or skin using one or more electric pulses from the pulse generator.

[0025] According to embodiments of the disclosed subject matter, the method further includes contacting the target tissue or skin with a heating device; and heating the target tissue or skin and / or contacting the target tissue or skin with an ultrasound generating device; and directing acoustic waves to the target tissue or skin. In some embodiments, the steps of directing acoustic

[0026] 514467368.1 -4- 072396.1110 PATENT waves to the target tissue or skin and directing acoustic waves to the target tissue or skin are performed simultaneously with the step of delivering the drug from the reservoir to the target tissue or skin. In some embodiments, the steps of directing acoustic waves to the target tissue or skin and directing acoustic waves to the target tissue or skin are performed before and / or after the step of delivering the drug from the reservoir to the target tissue or skin.

[0027] It is to be understood that both the foregoing general description and the following detailed description and drawings are examples and are provided for purpose of illustration and not intended to limit the scope of the disclosed subject matter in any manner.

[0028] The accompanying drawings, which are incorporated in and constitute part of this specification, are included to illustrate and provide a further understanding of the devices of the disclosed subject matter. Together with the description, the drawings serve to explain the principles of the disclosed subject matter.

[0029] BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The subject matter of the application will be more readily understood from the following detailed description when read in conjunction with the accompanying drawings, in which:

[0031] FIG. 1 shows a diagram of an illustrative pulse generating device according to embodiments of the present disclosure.

[0032] FIG. 2 is a diagram of an illustrative pulse generating device for drug delivery according to embodiment of the present disclosure.

[0033] FIG. 3 is diagram of a system including the pulse generating device of FIG. 2 including a second module according to embodiments of the present disclosure.

[0034] 514467368.1 -5- 072396.1110 PATENT

[0035] FIGS. 4 A and 4B are illustrations of different configurations of the second module according to embodiments of the present disclosure.

[0036] DETAILED DESCRIPTION

[0037] Reference will now be made in detail to embodiments of the disclosed subject matter, an example of which is illustrated in the accompanying drawings. The disclosed subject matter will be described in conjunction with the detailed description of the system.

[0038] As disclosed herein, the devices presented herein can be used for a variety of different purposes including but not limited gene therapy, tissue nano-transfection, pain mitigation, targeted cell delivery, tissue repair, tissue regeneration, or tissue stimulation.

[0039] In accordance with the disclosed subject matter, a device including a housing, the housing including a pulse generator disposed within the housing, a first electrode and a second electrode electrically coupled to the pulse generator, and an actuator coupled to the housing, the actuator configured to apply a mechanical force on the pulse generator, wherein the pulse generator is configured to convert the mechanical force into one or more electric pulses.

[0040] According to embodiments of the disclosed subject matter, the pulse generator is configured to produce one or more electric pulses with a peak voltage between 1 V and 50,000 V. According to embodiments of the disclosed subject matter, the one or more electric pulse has a pulse length between 1 nanosecond and 10 milliseconds. According to embodiments of the disclosed subject matter, the pulse generator comprises a piezo crystal, a spring-latch hammer, and electrical connections, wherein the piezo crystal comprises at least one of lead zirconate titanate (PZT), Barium Titanate (BT), quartz, and zinc oxide.

[0041] 514467368.1 -6- 072396.1110

[0042] PATENT

[0043] According to the disclosed subject matter, the device can further include a chip coupled to the housing, the chip including a top surface and a bottom surface, the top surface having a reservoir containing a drug therein and the bottom surface having at least one of hollow microchannels and hollow microneedles extending from the bottom surface, and wherein the first electrode is configured to be disposed in contact with the reservoir, wherein the second electrode is configured to be disposed in or on a target tissue or skin, and wherein the one or more electric pulses generated by the pulse generator are configured to drive delivery of the drug from the reservoir to the target tissue or skin. In embodiments, the reservoir is plastic. In some embodiments, the drug is at least one of charged biomolecules, DNA, and RNA. According to embodiments of the disclosed subject matter, the housing can include springs for releasably coupling to the chip.

[0044] According to embodiments described herein, described is a system including a first module including a device including a housing, the housing including a pulse generator disposed within the housing, a first electrode and a second electrode electrically coupled to the pulse generator, and an actuator coupled to the housing, the actuator configured to apply a mechanical force on the pulse generator, wherein the pulse generator is configured to convert the mechanical force into one or more electric pulses, and a chip coupled to the housing, the chip including a top surface and a bottom surface, the top surface having a reservoir containing a drug therein and the bottom surface having at least one of hollow microchannels and hollow microneedles extending from the bottom surface, and wherein the first electrode is configured to be disposed in contact with the reservoir, wherein the second electrode is configured to be disposed in or on a target tissue or skin, and wherein the one or more electric pulses generated by the pulse generator are configured to drive delivery of the drug from the reservoir to the target tissue or skin. The system can include a second module including at least one of a heating

[0045] 514467368.1 -7- 072396.1110

[0046] PATENT device and an ultrasound generating device. According to embodiment of the disclosed subject matter, the heating device is configured to directly contact the target or skin and / or the ultrasound generating device is configured to administer acoustic waves to the target tissue or skin and / or the second module comprises an opening configured to surround a bottom surface of the first module, and wherein the first module and the second module are configured to contact the target tissue or skin simultaneously. In some embodiments, the second module includes both the heating device and the ultrasound generating device. According to embodiments of the disclosed subject matter, the second module includes an external power source.

[0047] In accordance with another aspect of the disclosed subject matter, a method of drug delivery includes contacting a target tissue or skin with a device, the device including: a pulse generator disposed within the housing, an actuator coupled to the housing, the actuator configured to apply a mechanical force on the pulse generator a first electrode and a second electrode electrically coupled to the pulse generator, and a chip configured to be releasably coupled to the housing, the chip including a top surface and a bottom surface, the top surface having a reservoir comprising a drug and the bottom surface having at least one of hollow microchannels and hollow microneedles extending from the bottom surface, wherein the first electrode is configured to be disposed in contact with the reservoir, wherein the second electrode is configured to be disposed in or on a target tissue or skin, and wherein the pulse generator is configured to convert the mechanical force to produce one or more electric pulses, activating the pulse generator using the actuator; and delivering the drug from the reservoir to the target tissue or skin using one or more electric pulses from the pulse generator.

[0048] According to embodiments of the disclosed subject matter, the method further includes contacting the target tissue or skin with a heating device; and heating the target tissue or skin

[0049] 514467368.1 -8- 072396.1110

[0050] PATENT and / or contacting the target tissue or skin with an ultrasound generating device; and directing acoustic waves to the target tissue or skin. In some embodiments, the steps of directing acoustic waves to the target tissue or skin and directing acoustic waves to the target tissue or skin are performed simultaneously with the step of delivering the drug from the reservoir to the target tissue or skin. In some embodiments, the steps of directing acoustic waves to the target tissue or skin and directing acoustic waves to the target tissue or skin are performed before and / or after the step of delivering the drug from the reservoir to the target tissue or skin.

[0051] Solely for purpose of illustration, an embodiment of a self-powered pulse generator is shown schematically in FIG. 1. The examples herein are not intended to limit the scope of the disclosed subject matter in any manner. Particularly, and as illustrated, the device 100 includes a housing 101, a pulse generator 102 disposed within the housing, electrical connections 103 coupled to the pulse generator 102, and a force generating mechanism 105 coupled to the pulse generator 102. The pulse generator 102 can be coupled with electrical connections, as further described herein.

[0052] Referring still to FIG. 1, the pulse generator 102 includes a piezoelectric crystal 110 disposed within a case 111. The piezoelectric crystal 110 is coupled to the force generating mechanism 105. The piezoelectric crystal 110 can be configured to convert mechanical energy to electrical energy. As illustrated in FIG. 1, the force generating mechanism 105 includes a hand toggle or trigger that can be manually actuated by a user, such as with a depressive force by a thumb of a user. In embodiments described herein, the piezoelectric crystal 110 is configured to convert a mechanical force imparted on the piezoelectric crystal 110 by the hand toggle or actuator into an electric pulse that is transmitted through the electrical connections to the electrodes 104. A spring-latch hammer 107 can be coupled to the piezoelectric crystal 110 to assist with transfer of mechanical energy from the force generating mechanism 105 to the

[0053] 514467368.1 -9- 072396.1110

[0054] PATENT piezoelectric crystal 110. Additionally, electrical connections 106 can be coupled to transfer the one or more electric pulses generated by the piezoelectric crystal 110 to the electrodes 104.

[0055] A first end of the electrical connections 103 is connected to the pulse generator 102. A second end of the electrical connections 103 can be connected to electrodes 104 opposite the first end. Alternatively, the second end of the electrical connections 103 can remain unconnected to any additional component. In some embodiments, one or more of the electrodes 104 can be coupled directly to the housing 101 such that the position of a respective electrode 104 is fixed relative to the housing 101 and one or more of the electrodes 104 can be connected to the housing by way of the electrical connections 103, leads or other suitable electrical connections. Such configuration can permit the respective electrode 104 to be freely positionable relative to the housing 101 by way of the lead or other electrical connection. For example, electrical connections 103 can comprise wires made of a suitable electrically conductive material, such as copper. As illustrated in the example of FIG. 2 further discussed below, a first electrode 204a is disposed within the housing 201 such that the position of the first electrode 204a is fixed and coupled to the housing 201 by an electrical lead 203. In contrast, a second electrode 204b is freely positionable relative to the housing and the first electrode 204a, as shown in FIG. 2.

[0056] The force generating mechanism 105 can include an actuator such as a toggle connected to a spring. The actuator is configured to apply a mechanical force to the pulse generator upon the application of a force by the user. The spring acts to reset the position of the actuator such that a user can apply one or subsequent forces to the trigger or actuator. Each depression of the force generating mechanism creates a force on the pulse generator that creates one electric pulse. In this way, a user of the device can create any number of desired pulses based on a

[0057] 514467368.1 -10- 072396.1110

[0058] PATENT corresponding number of depressions of the force generating mechanism 105. Likewise, a user can control the timing of the pulses with the force generating mechanism 105.

[0059] In embodiments described herein, the piezoelectric pulse generator can include a piezo crystal, a spring-latch hammer, and electrical connections. In some embodiments the piezo crystal can include at least one of lead zirconate titanate (PZT), Barium Titanate (BT), quartz, and zinc oxide. Other suitable materials for the piezo crystal can include crystalline materials including but not limited to langasite, gallium orthophosphate, lithium niobate, berlinite, topaz, or other crystalline materials known in the art, ceramic materials including but not limited to potassium niobate, sodium tungstate, or other ceramic materials known in the art.

[0060] Referring to FIG. 1, the pulse generator 102 can be configured to produce one or more electric pulses with a pulse length between one nanosecond and ten milliseconds. The pulse width is controlled by the properties of the piezo crystal and the force applied. The pulse generator can be configured to generate one of more electric pulses with peak voltages between one volt and 50,000 volts. Like the pulse width, the peak voltage can be controlled by the selection of the material for the piezo crystal. Selection of an appropriate piezo crystal material can be made based on the desired application of the device. While control of the electric pulse is illustrated as being controlled by manual depressions of the force generating mechanism 105, other devices that control the pulse generator are within the scope of the disclosed subject matter. For example, the housing 101 can be include a circuit board including a microprocessor and other electronics that can be configured to control a mechanical force generator mechanism within the housing to impart mechanical energy on the pulse generator. The controller can be configured to control the number of pulses and the timing between successive pulses to control the pulse generator automatically, which can be a predetermined value as desired by the end use of the device. In some embodiments, the circuit board further includes communication

[0061] 514467368.1 -11- 072396.1110 PATENT circuitry configured to communicate with an external control device through known mechanism in the art including but not limited to radio frequency (RF), Bluetooth, or near-field communication (NFC). The external control device can be configured to transmit instructions including the number of pulses to be delivered and the timing between successive pulses to the microprocessor. External control device can be a mobile phone, a computer, or another LED controller as are known in the art.

[0062] As shown in FIG. 1, the housing 101 can be made of a suitable material, including but limited to plastics or polymers, to maintain a light weight and make the device easy to manufacture and lightweight. In some embodiments, the device 100 weighs less than 5 grams. In other embodiments, the devices less than 10 grams.

[0063] Referring now to FIG. 2, an embodiment of a self-powered pulse generator system 200 is illustrated. System 200 can include a device 250 which includes a housing 201, a pulse generator 202 disposed within the housing 201, electrical leads 203 coupled to the pulse generator 202, and a force generating mechanism 205, which are each configured substantially the same as described above with reference to FIG. 1. Device 250 further comprises electrodes 204a / b connected to the pulse generator by the electrical leads 203. One of the electrodes, the first electrode 204a, is disposed in a fixed position within the housing 201 and another electrode, the second electrode 204b, is coupled to the housing 201 and is freely positionable outside of the housing 201. The system 200 further includes a chip 220. The chip 220 can be fixedly and / or releasably coupled to the housing 210 at a distal end of the housing 201. The housing can include a device to maintain the connection of the chip 220 to the housing 201, such as at least one spring and at least one flange.

[0064] 514467368.1 -12- 072396.1110

[0065] PATENT

[0066] The chip 220 comprises a base substrate 221, a reservoir 222, and one or more delivery channels 223. In some embodiments, the one or more delivery channels includes one of hollow micro-channels or hollow micro-needles. The reservoir 222 can be disposed on a top surface of the base substrate 221 and can comprise a solution disposed within the reservoir 222, such as a drug. The reservoir 222 can be formed of a polymer, plastic, or any suitable material known in the art. In embodiments described herein, the solution can include a drug that can include at least one or more of charged biomolecules, DNA, RNA, charged lipid nanoparticles, or inorganic nanoparticles. The base substrate 221 and the one or more delivery channels 223 can be integrally formed or can be separate components coupled together. The base substrate 221 and the one or more delivery channels 223 can be comprised of any suitable material known in the art including but limited to silicon, polymers, or metals.

[0067] Referring still to FIG. 2, the chip 220 is connected to the housing 201 at a distal end of the housing 201 such that the first electrode 204a disposed within the housing 201 is connected to or disposed within the reservoir 222. Placement of the first electrode 204a in connection with the reservoir 222 electrically couples the reservoir to the pulse generator 202 and allows for one or more electric pulses generated by the pulse generator to be applied across the reservoir between the electrodes 204a and 204b.

[0068] The system according to the disclosed subject matter can be used in a variety of applications and can be portable. In some embodiments, the system 200 is configured for use as a tissue nano-transfection. Reservoir 222 can include a drug solution having at least one of a charged biomolecule, DNA, and RNA. The chip 220 can be coupled to the housing 201 to place the reservoir 222 in direct connection with the first electrode 204a disposed within the housing 201. The second electrode 204b is disposed freely outside of the housing 201 and is configured to be inserted into a skin or other tissue 400 of a patient. The one or more delivery

[0069] 514467368.1 -13- 072396.1110

[0070] PATENT channels 223 are configured to be placed in or on a skin or tissue 400 near the second electrode 204b. Application of a force to the force generating mechanism 205 causes the pulse generator to convert the mechanical energy into an electric pulse that is transmitted through the electric leads 203 to create an electric field across the reservoir 222 and the skin or tissue. The electric field increases the permeability of a cell membrane of the patient and drives a flow of drug located within the reservoir through the delivery channels into the skin or tissue of the patient.

[0071] In some embodiment, the pulse generator is configured to produce one or more electric pulses with a pulse width between 1 nanosecond and 10 milliseconds. Electric pulses of widths between 1 nano second and 10 milliseconds diminish the risk of tissue damage by reducing the thermal effects of the electric pulses on the tissue. Control of the dosage of the drug imparted can be controlled by the number of electric pulses generated and the pulse length.

[0072] Referring now to FIG. 3, a system 300 illustrating a tissue nano-transfection device is shown. The system 300 includes a first module 320 having a system 200 as described above, and a second module 310. Second module 310 can include at least one of a heating module

[0073] 301, an ultrasound generating module 302, and a power source 303. As illustrated in FIG. 3, second module 310 includes both the heating module 301 and the ultrasound generating module

[0074] 302. The heating module 301 includes a bottom surface configured to be placed in contact with a skin surface of a patient to apply heat to the skin. The heating module 301 is configured to generate heat to increase the temperature of the patient’s skin and tissue proximate to the heating module 301. Suitable heating modules can include heating pads or other heating elements known in the art. The heating mechanism can be electrical, chemical, or water based. The heating module can be configured to generate any temperature up to 50 degrees Celsius. The increase in temperature increases fluidity of the cell membrane of the patient, which promotes cells is absorb more of the drug solution from the reservoir during tissue nano-

[0075] 514467368, i -14- 072396.1110

[0076] PATENT transfection. Additionally, an increase in local temperature of the skin and tissue proximate the heating module 301 induces vasodilation and enhances diffusion of biomolecules within the drug which also improves the efficiency of the treatment and accelerates wound healing of the patient.

[0077] The ultrasound generating module 302 is configured to generate and transmit acoustic energy to the skin and tissues of the patient proximate the ultrasound generating module 302. The ultrasound generating module can be configured to generate waves with a frequency up to lOOKHz and a power up to 1W. Suitable ultrasound generators can be configured to convert alternating current from a power supply into high voltage pulses of energy. The ultrasound generator can be further configured to convert the high voltage pulses into a mechanical vibration used to output the acoustic energy from the ultrasound generator using suitable structures as known in the art. The application of acoustic energy stimulates the localized tissues of the patient to facilitate the diffusion of the biomolecules within the drug solution and increases the activity of the biomolecules to enhance the overall therapeutic efficacy of the treatment.

[0078] The heating module 301 and ultrasound generating module 302 are respectively coupled to a power source 303, such as an external power source or power bank, to power the second module 310. Power source 303 can be a fixed power source including but limited to a wall socket, or can be a mobile power source, including but limited to a power bank, a battery pack, or other power sources known in the art. Likewise, connection between the heating module 301 and the ultrasound generating module 302 and the external power source can be achieved through any know connection in the art, such as a USB or USB-C cable. While one power source is depicted in FIG. 3, each of the heating module 301 and the ultrasound generating module 302 can have their own respective power sources.

[0079] 514467368.1 -15- 072396.1110

[0080] PATENT

[0081] As shown in FIG. 3, chip 220 can be releasably coupled to the housing 201 using spring 305 and mechanical retentions 306. The chip 220 can be configured for single use and / or can be disposable while the device is configured to be reusable. The releasable coupling within the housing 201 is configured to permit a disposable chip 220 to be securely coupled to the housing 201 prior to, during, and after a tissue nano-transfection procedure. After the procedure is completed with the device, the releasable coupling is configured to allow the chip 220 to be disconnected from the housing 201 and replaced by a new chip.

[0082] Referring to FIG. 4A, the second module 310 has a substrate formed of a generally rectangular shape including a square opening 322 through the middle. The opening 322 is configured to accommodate and receive at least a portion of the first module 320 therethrough, such that both the first module 320 and the second module 310 can be disposed on the skin simultaneously. In use, the second module 310 can be placed onto the skin of a user and the first module 320 is then placed within the square opening 322 such that all of the one or more delivery channels 223, the heating module 301, and the ultrasound generating module 302 are all in contact with the skin of the patient. While depicted as a square, the shape of the opening 330 is not limited to such and can be any shape that can accommodate the shape of the portion of housing 201 and chip 220, which can, for example, be any suitable shape including a circle, oval, or a polygon like a triangle, square, rectangle, rhombus, pentagon, etc.

[0083] Second module 310 can be controlled by an external control device 370, which can be a mobile phone, a computer, or any other control device as are known in the art. External control device 370 can be configured to control settings for either or both of the heating module 301 and the ultrasound generating module 302. For example, the external control device 370 can set a temperature and time duration for the heating module 301 and a frequency, power, and time duration for the ultrasound generating module 302. In some embodiments, the heating

[0084] 514467368.1 -16- 072396.1110 PATENT module 301 and the ultrasound generating module 302 are not controlled by the external control device 370 and instead include their own control mechanisms. The external control device 370 can be configured to monitor the time of the procedure and the number of pulses applied.

[0085] FIG. 4B illustrates a different configuration of a second module 350 for use with the first module 320 as described above. Second module 350 includes a heating module 301 and an ultrasound generating module 302 that are configured to perform substantially the same functions as the modules in second module 310. The second module 350 of FIG. 4B includes a bottom surface that is substantially planar and lacks an opening to accommodate the first module 320, which is one difference from the second module 310 of FIG. 4A. In this configuration, the second module 350 can be placed on the skin prior to or after the tissue nanotransfection procedure using the first module 320.

[0086] A method of using one or more of the self-powered pulse generators and systems described herein can be inferred and understood by one of ordinary skill in the art based on the descriptions provided herein.

[0087] Embodiments disclosed herein include a device including a housing, the housing including a pulse generator disposed within the housing, a first electrode and a second electrode electrically coupled to the pulse generator, and an actuator coupled to the housing, the actuator configured to apply a mechanical force on the pulse generator, wherein the pulse generator is configured to convert the mechanical force into one or more electric pulses.

[0088] Aspects of the disclosed subject matter are set out in the claims and additional features are further described in the dependent claims and within the disclosure. The additional features can be provided in combination within a single pulse generating device. Moreover, a pulse

[0089] 514467368.1 -17- 072396.1110 PATENT generating device can be provided that combines features of the independent claims together with any of the features of the dependent claims.

[0090] Embodiment A: A device including a housing, the housing including a pulse generator disposed within the housing, a first electrode and a second electrode electrically coupled to the pulse generator, and an actuator coupled to the housing, the actuator configured to apply a mechanical force on the pulse generator, wherein the pulse generator is configured to convert the mechanical force into one or more electric pulses.

[0091] Embodiment B: A system including a system including a first module including a device including a housing, the housing including a pulse generator disposed within the housing, a first electrode and a second electrode electrically coupled to the pulse generator, and an actuator coupled to the housing, the actuator configured to apply a mechanical force on the pulse generator, wherein the pulse generator is configured to convert the mechanical force into one or more electric pulses, and a chip coupled to the housing, the chip including a top surface and a bottom surface, the top surface having a reservoir containing a drug therein and the bottom surface having at least one of hollow microchannels and hollow microneedles extending from the bottom surface, and wherein the first electrode is configured to be disposed in contact with the reservoir, wherein the second electrode is configured to be disposed in or on a target tissue or skin, and wherein the one or more electric pulses generated by the pulse generator are configured to drive delivery of the drug from the reservoir to the target tissue or skin, and a second module including at least one of a heating device and an ultrasound generating device.

[0092] Embodiment C: a method of drug delivery includes contacting a target tissue or skin with a device, the device including: a pulse generator disposed within the housing, an actuator

[0093] 514467368.1 -18- 072396.1110 PATENT coupled to the housing, the actuator configured to apply a mechanical force on the pulse generator a first electrode and a second electrode electrically coupled to the pulse generator, and a chip configured to be releasably coupled to the housing, the chip including a top surface and a bottom surface, the top surface having a reservoir comprising a drug and the bottom surface having at least one of hollow microchannels and hollow microneedles extending from the bottom surface, wherein the first electrode is configured to be disposed in contact with the reservoir, wherein the second electrode is configured to be disposed in or on a target tissue or skin, and wherein the pulse generator is configured to convert the mechanical force to produce one or more electric pulses, activating the pulse generator using the actuator; and delivering the drug from the reservoir to the target tissue or skin using one or more electric pulses from the pulse generator.

[0094] Each of embodiments A, B, and C can have one or more of the following additional elements in any combination:

[0095] Element 1 : a chip coupled to the housing, the chip including a top surface and a bottom surface, the top surface having a reservoir containing a drug therein and the bottom surface having at least one of hollow microchannels and hollow microneedles extending from the bottom surface, and wherein the first electrode is configured to be disposed in contact with the reservoir, wherein the second electrode is configured to be disposed in or on a target tissue or skin, and wherein the one or more electric pulses generated by the pulse generator are configured to drive delivery of the drug from the reservoir to the target tissue or skin.

[0096] Element 2: wherein the housing further comprises springs for releasably coupling to the chip.

[0097] Element 3: further comprising a second chip, the second chip couplable to the housing.

[0098] 514467368.1 -19- 072396.1110

[0099] PATENT

[0100] Element 4: wherein the drug is at least one of charged biomolecules, DNA, and RNA.

[0101] Element 5: wherein the pulse generator is configured to produce one or more electric pulses with a peak voltage between 1 V and 50,000 V.

[0102] Element 6: wherein the one or more electric pulse has a pulse length between 1 nanosecond and lOmilliseconds.

[0103] Element 7: wherein the pulse generator comprises a piezo crystal, a spring-latch hammer, and electrical connections.

[0104] Element 8: wherein the piezo crystal comprises at least one of lead zirconate titanate (PZT), Barium Titanate (BT), quartz, and zinc oxide. Element 9: wherein the heating device is configured to directly contact the target or skin.

[0105] Element 10: wherein the ultrasound generating device is configured to administer acoustic waves to the target tissue or skin.

[0106] Element 11 : wherein the second module includes both the heating device and the ultrasound generating device.

[0107] Element 12: wherein the second module includes an external power source.

[0108] Element 13: wherein the second module comprises an opening configured to surround a bottom surface of the first module, and wherein the first module and the second module are configured to contact the target tissue or skin simultaneously.

[0109] 514467368.1 -20- 072396.1110 PATENT

[0110] Element 14: further comprising: contacting the target tissue or skin with a heating device; and heating the target tissue or skin.

[0111] Element 15: further comprising: contacting the target tissue or skin with an ultrasound generating device; and directing acoustic waves to the target tissue or skin.

[0112] Element 16: wherein the steps of directing acoustic waves to the target tissue or skin and directing acoustic waves to the target tissue or skin are performed simultaneously with the step of delivering the drug from the reservoir to the target tissue or skin.

[0113] Element 17: wherein the steps of directing acoustic waves to the target tissue or skin and directing acoustic waves to the target tissue or skin are performed before and / or after the step of delivering the drug from the reservoir to the target tissue or skin.

[0114] While the disclosed subject matter is described herein in terms of certain preferred embodiments, those skilled in the art will recognize that various modifications and improvements can be made to the disclosed subject matter without departing from the scope thereof. Moreover, although individual features of one embodiment of the disclosed subject matter can be discussed herein or shown in the drawings of the one embodiment and not in other embodiments, it should be apparent that individual features of one embodiment can be combined with one or more features of another embodiment or features from a plurality of embodiments.

[0115] In addition to the various embodiments depicted and claimed, the disclosed subject matter is also directed to other embodiments having any other possible combination of the features disclosed and claimed herein. As such, the particular features presented herein can be combined with each other in other manners within the scope of the disclosed subject matter

[0116] 514467368.1 -21- 072396.1110 PATENT such that the disclosed subject matter includes any suitable combination of the features disclosed herein. Thus, the foregoing description of specific embodiments of the disclosed subj ect matter has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the disclosed subject matter to those embodiments disclosed.

[0117] Unless otherwise indicated, all numbers expressing quantities and the like in the present specification and associated claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by the embodiments of the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claim, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

[0118] One or more illustrative embodiments incorporating various features are presented herein. Not all features of a physical implementation are described or shown in this application for the sake of clarity. It is understood that in the development of a physical embodiment incorporating the embodiments of the present invention, numerous implementation-specific decisions must be made to achieve the developer's goals, such as compliance with system- related, business-related, government-related and other constraints, which vary by implementation and from time to time. While a developer's efforts might be time-consuming, such efforts would be, nevertheless, a routine undertaking for those of ordinary skill in the art and having benefit of this disclosure.

[0119] 514467368.1 -22- 072396.1110 PATENT

[0120] While various systems, tools and methods are described herein in terms of “comprising” various components or steps, the systems, tools and methods can also “consist essentially of’ or “consist of’ the various components and steps.

[0121] As used herein, the phrase “at least one of’ preceding a series of items, with the terms “and” or “or” to separate any of the items, modifies the list as a whole, rather than each member of the list (i.e., each item). The phrase “at least one of’ allows a meaning that includes at least one of any one of the items, and / or at least one of any combination of the items, and / or at least one of each of the items. By way of example, the phrases “at least one of A, B, and C” or “at least one of A, B, or C” each refer to only A, only B, or only C; any combination of A, B, and C; and / or at least one of each of A, B, and C.

[0122] All numbers and ranges disclosed above can vary by some amount. Whenever a numerical range with a lower limit and an upper limit is disclosed, any number and any included range falling within the range is specifically disclosed. In particular, every range of values (of the form, “from about a to about b,” or, equivalently, “from approximately a to b,” or, equivalently, “from approximately a-b”) disclosed herein is to be understood to set forth every number and range encompassed within the broader range of values. Also, the terms in the claims have their plain, ordinary meaning unless otherwise explicitly and clearly defined by the patentee. Moreover, the indefinite articles “a” or “an,” as used in the claims, are defined herein to mean one or more than one of the elements that it introduces. If there is any conflict in the usages of a word or term in this specification and one or more patent or other documents that can be incorporated herein by reference, the definitions that are consistent with this specification should be adopted.

[0123] 514467368.1 -23- 072396.1110

[0124] PATENT

[0125] It will be apparent to those skilled in the art that various modifications and variations can be made in the system of the disclosed subject matter without departing from the spirit or scope of the disclosed subject matter. Thus, it is intended that the disclosed subject matter include modifications and variations that are within the scope of the appended claims and their equivalents.

[0126] 514467368.1 -24-

Claims

072396.1110PATENTCLAIMSWHAT IS CLAIMED IS:

1. A generator device comprising: a housing, the housing including: a pulse generator disposed within the housing, a first electrode and a second electrode electrically coupled to the pulse generator, and an actuator coupled to the housing, the actuator configured to apply a mechanical force on the pulse generator, wherein the pulse generator is configured to convert the mechanical force into one or more electric pulses.

2. The device of claim 1, further comprising a chip coupled to the housing, the chip including a top surface and a bottom surface, the top surface having a reservoir containing a drug therein and the bottom surface having at least one of hollow microchannels and hollow microneedles extending from the bottom surface, and wherein the first electrode is configured to be disposed in contact with the reservoir, wherein the second electrode is configured to be disposed in or on a target tissue or skin of a patient, and wherein the one or more electric pulses generated by the pulse generator are configured to drive delivery of the drug from the reservoir to the target tissue or skin.

3. The device of claim 2, wherein the housing further comprises springs for releasably coupling to the chip.

4. The device of claim 2, further comprising a second chip attachable to the device5. The device of claim 2, wherein the drug is at least one of charged biomolecules, DNA, and RNA.514467368.1 -25-072396.1110PATENT6. The device of claim 1, wherein the pulse generator is configured to produce the one or more electric pulses with a peak voltage between 1 V and 50,000 V.

7. The device of claim 6, wherein the one or more electric pulses has a pulse length between 1 nanosecond and 10 milliseconds.

8. The device of claim 1, wherein the pulse generator comprises a piezo crystal, a spring-latch hammer, and electrical connections.

9. The device of claim 8, wherein the piezo crystal comprises at least one of lead zirconate titanate (PZT), Barium Titanate (BT), quartz, and zinc oxide.

10. A system comprising: a first module including a device having: a housing, the housing including: a pulse generator disposed within the housing, a first electrode and a second electrode electrically coupled to the pulse generator, and a chip coupled to the housing, the chip including a top surface and a bottom surface, the top surface having a reservoir containing a drug therein and the bottom surface having at least one of hollow microchannels and hollow microneedles extending from the bottom surface, wherein the first electrode is configured to be disposed in contact with the reservoir, wherein the second electrode is configured to be disposed in or on a target tissue or skin of a patient, and an actuator coupled to the housing, the actuator configured to apply a mechanical force on the pulse generator, wherein the pulse generator is configured to convert the mechanical force into one or more electric pulses, wherein the one or514467368.1 -26-072396.1110PATENT more electric pulses generated by the pulse generator are configured to drive delivery of the drug from the reservoir to the target tissue or skin; and a second module including at least one of a heating device and an ultrasound generating device, wherein the heating device is configured to directly contact the target tissue or skin of the patient.

11. The system of claim 10, wherein the ultrasound generating device is configured to generate and administer acoustic waves to the target tissue or skin of the patient.

12. The system of claim 10, wherein the second module includes both the heating device and the ultrasound generating device.

13. The system of claim 12, wherein the second module further includes an external power source.

14. The system of claim 12, wherein the second module comprises a substrate defining an opening configured to surround a bottom surface of the first module, and wherein the first module and the second module are configured to contact the target tissue or skin of the patient simultaneously.

15. The system of claim 12, wherein the system is portable.

16. A method of performing tissue nano-transfection comprising: contacting a target tissue or skin of a patient with a portable generator device, the device including: a pulse generator disposed within a housing, an actuator coupled to the housing, the actuator configured to apply a mechanical force on the pulse generator,514467368.1 -27-072396.1110PATENT a first electrode and a second electrode electrically coupled to the pulse generator, and a chip configured to be releasably coupled to the housing, the chip including a top surface and a bottom surface, the top surface having a reservoir comprising a drug and the bottom surface having at least one of hollow microchannels and hollow microneedles extending from the bottom surface, wherein the first electrode is configured to be disposed in contact with the reservoir, wherein the second electrode is configured to be disposed in or on the target tissue or skin of the patient, and wherein the pulse generator is configured to convert the mechanical force to produce one or more electric pulses, activating the pulse generator using the actuator; and delivering the drug from the reservoir via the at least one of hollow microchannels and hollow microneedles to the target tissue or skin using one or more electric pulses from the pulse generator.

17. The method of claim 16, further comprising: contacting the target tissue or skin with a heating device; and heating the target tissue or skin.

18. The method of claim 17, further comprising: contacting the target tissue or skin with an ultrasound generating device; and directing acoustic waves to the target tissue or skin.

19. The method of claim 18, wherein the steps of directing acoustic waves to the target tissue or skin and directing acoustic waves to the target tissue or skin are performed514467368.1 -28-072396.1110PATENT simultaneously with the step of delivering the drug from the reservoir to the target tissue or skin.

20. The method of claim 19, wherein the steps of directing acoustic waves to the target tissue or skin and directing acoustic waves to the target tissue or skin are performed before and / or after the step of delivering the drug from the reservoir to the target tissue or skin.514467368.1 -29-

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