ELECTROPORATION DEVICE WITH IMPROVED SIGNAL GENERATOR

Abstract

A portable electroporation device having an improved signal generator; the signal generator includes a main winding and multiple secondary windings where the multiple secondary windings are coupled together in a series configuration; a storage capacitor and flyback diode are coupled to each of the multiple secondary windings; the signal generator includes a signal amplifier and a power switch; the power switch is configured to supply a voltage from a power source through the main winding.

Description

ELECTROPORATION DEVICE WITH IMPROVED SIGNAL GENERATOR CROSS REFERENCE TO RELATED APPLICATIONS This patent application claims priority from U.S. provisional patent application No. 62 / 271,955, filed on December 28, 2015. The aforementioned application is incorporated herein by this reference. BACKGROUND OF THE INVENTION The modalities of the description refer to an electroporation device with an improved signal generator to generate high voltage electroporation signals. BRIEF DESCRIPTION OF THE INVENTION Medical devices, such as electroporation devices, require high-voltage generators to provide the necessary power supply. During the electroporation process, the electrodes in contact with the target tissue require electrical power at a specific voltage and amperage to produce the desired electroporation effects (e.g., 200 V at 0.5 Amps). Generally, the high voltage levels required during electroporation necessitate a voltage generator that includes several high-capacity capacitors. These capacitors, however, occupy a significant amount of physical space and require lengthy charging times before the electroporation process can begin. These attributes pose a challenge for portable units, where size and weight must be kept to a minimum.Furthermore, long charging times can hinder the user's ability to deliver electroporation treatment accurately and on time. Additionally, capacitor-based systems suffer from signal degradation over time. The description provides a signal generator that generates multiple lower voltages and combines them in series to create a high voltage. In one aspect, a portable unit for use in an electroporation device, the portable unit includes a housing and a signal amplifier within the housing. The signal amplifier comprises a main winding, multiple secondary windings coupled together in a series configuration, with a storage capacitor and a flyback diode coupled to each of the multiple secondary windings, and an assembly having multiple electrodes in electrical communication with the signal amplifier. MA / a / ZUZZ / UU l U14 In another aspect, an electroporation device includes a housing and a signal generator located within the housing. The signal generator includes a signal amplifier having a main winding and multiple secondary windings coupled together in a series configuration, where a storage capacitor and a flyback diode are coupled to each of the multiple secondary windings, a power supply and a power switch configured to supply a voltage from a power supply across the main winding, and an assembly having one or more electrodes in electrical communication with the signal generator. In yet another aspect, an electroporation system includes a base station and a portable unit removably attached to the base station. The portable unit includes a housing, an injection assembly, a power supply, and a signal generator located within the portable unit housing and in operational communication with the injection assembly. The signal generator includes a signal amplifier having a main winding and multiple secondary windings coupled in a series configuration, where a storage capacitor and a flyback diode are coupled to each of the multiple secondary windings, and a power switch configured to supply a voltage from the power supply across the main winding, and an assembly having at least one electrode extending from there in electrical communication with the signal generator. BRIEF DESCRIPTION OF THE FIGURES Figure 1 is a schematic view of an electroporation device showing a portable unit and a base unit in a coupled configuration. Figure 2 is a diagram of the voltage amplifier of Figure 1, according to some modalities. Figure 3 is a block diagram of the signal generator and power supply of Figure 1, according to some modalities. DETAILED DESCRIPTION OF THE INVENTION Before explaining the description methods in detail, it should be understood that the description is not limited to the construction details and component arrangement established in the following description or illustrated in the following figures. The description allows for other methods and can be implemented or carried out in various ways. It should also be noted that multiple different structural components can be used to implement the description. Furthermore, as described in the following paragraphs, the specific configurations illustrated in the figures are intended to exemplify different ways of describing the description. Alternative configurations are possible. Agent may mean a polypeptide, a polynucleotide, a small molecule, or any combination thereof. The agent may be a recombinant nucleic acid sequence encoding an antibody, a fragment thereof, a variant thereof, or a combination thereof, as detailed in PCT / US2014 / 070188, which is incorporated herein by reference. Agent may mean a composition comprising a polypeptide, a polynucleotide, a small molecule, or any combination thereof. The composition may comprise a recombinant nucleic acid sequence encoding an antibody, a fragment thereof, a variant thereof, or a combination thereof, as detailed in PCT / US2014 / 070188, which is incorporated herein by reference. The agent may be formulated in water or in a buffer, for example. The buffer may be sodium citrate saline (SSC) or phosphate-buffered saline (PBS), for example.The ionic content of buffers can increase conductivity, which may result in increased current flow in the target tissue. The concentration of the formulated polynucleotide can range from 1 pg to 20 mg / ml. For example, the concentration of the formulated polynucleotide can be 1 pg / ml, 10 pg / ml, 25 pg / ml, 50 pg / ml, 100 pg / ml, 250 pg / ml, 500 pg / ml, 750 pg / ml, 1 mg / ml, 10 mg / ml, 15 mg / ml, or 20 mg / ml. A peptide, protein, or polypeptide as used herein may mean a linked sequence of amino acids and may be natural, synthetic, or a modification or combination of natural and synthetic. Polynucleotide, oligonucleotide, or nucleic acid as used herein means at least two nucleotides covalently linked. A polynucleotide may be single-stranded or double-stranded, or may contain portions of both double-stranded and single-stranded sequences. The polynucleotide may be DNA (either genomic or cDNA), RNA, or a hybrid. The polynucleotide may contain combinations of deoxyribo- and ribonucleotides and combinations of bases including uracil, adenine, thymine, cytosine, guanine, inosine, xanthine, hypoxanthine, isocytosine, isoguanine, and synthetic or non-naturally derived nucleotides and nucleosides. Polynucleotides can serve as vectors. Polynucleotides can be obtained through chemical synthesis or recombinant methods. The term "vector" as used herein means a nucleic acid sequence containing an origin of replication. A vector may be a viral vector, bacteriophage, bacterial artificial chromosome, or yeast artificial chromosome. A vector may be a DNA or RNA vector. A vector may be an extrachromosomal self-replicating vector and, preferably, a DNA plasmid. The term electroporation (EP) as used herein refers to the use of an electric field pulse to induce reversible microscopic pathways (pores) in a biomembrane; their presence allows agents to pass from one side of the cell membrane to the other. This description relates to a portable unit 100 for an electroporation device 104 that includes an improved signal generator 32 for producing a predetermined electroporation signal. Figure 1 illustrates the electroporation device 104, which includes a base unit 109 and a portable unit 100 that can be removably coupled to the base unit 108. The base unit 109 is typically placed on a table or other flat surface and is electrically connected to and can charge the power supply 34 when the portable unit 100 and the base unit 109 are coupled or in a coupled configuration. Figure 1 illustrates the portable electroporation device 100, which includes a housing 108, an electrode assembly 112 coupled to the housing 108, a power supply 34 located within the housing 108, and a signal generator 32 in electrical communication with the power supply 34 and the electrode assembly 112. The portable device 100 also includes an injection assembly 110 for administering the agent to the target tissue using a hypodermic needle 111. During use, the electroporation device 100 facilitates the introduction of the agent into the cells of a target tissue (e.g., skin or muscle) of a mammal using electroporation pulses generated by the signal generator 32. The portable device 100 requires the generation of very high voltage values ​​(e.g., 200 Volts) to generate the electroporation pulses.The portable 100 unit uses the signal generator 32 to generate high voltage values ​​from a power source (e.g., lithium-ion batteries) that supplies a lower voltage value. In Figure 1, the housing 108 of the handpiece 100 is formed by two halves or members 116 coupled together to form a volume 120 between them. Specifically, the members 116 form a pistol-shaped handpiece with a top portion 124 having a front end 128 and a rear end 132, and a handle portion 136 extending from the top portion 124 to form a distal end. In some embodiments, the handle portion 136 may also include a trigger 140 or other user inputs to allow the user to command the delivery of the electroporation signal to the target tissue. Although the housing 108 of the handpiece 100 is illustrated as pistol-shaped, it should be understood that the housing 108 may have additional shapes or be adapted to different handle styles. The electrode assembly 112 includes multiple electrodes 142, each extending outward from the front end 128 of the upper portion 124 of the housing 108. Each electrode 142 is in electrical communication with the signal generator 32 and is configured to transmit the electroporation signal to the target tissue during operation. ΜΛ / a / ZUZZ / UU l U14 of device 104. Figures 1 and 3 illustrate a signal generator 32. The signal generator 32 includes, among other components, a power switch 36 and a voltage amplifier 5. In the illustrated embodiment, the signal generator 32 is positioned within the housing 108 such that the overall center of gravity (CG) of the portable unit 100 is located near the intersection of the handle portion 136 and the top portion 124. In some embodiments, the top portion 124 of the housing 108 may define an axis A extending longitudinally through it such that an axis B positioned perpendicular to axis A and passing through the center of gravity (CG) also passes through the handle portion 136 of the housing 108 (see Figure 1). Figure 2 illustrates a voltage amplifier 5 that includes, among other components, an amplifier housing 10, a main winding 12, and multiple secondary windings 14A-E. The main winding 12 and the multiple secondary windings 14A-E are located inside the amplifier housing 10. In the configuration illustrated in Figure 1, the multiple secondary windings 14A-E include five secondary windings. In other configurations, the multiple secondary windings 14A-E may include more or fewer secondary windings. Additionally, in other configurations, the voltage amplifier 5 may include more than one main winding. The first and second inputs 16A-B provide connections between the main windings 12 and one or more components external to the amplifier housing 10. The voltage across the main winding 12 is equal to the voltage difference between the first and second inputs 16A-B. The voltage across each main winding is equal to the voltage across the main winding 12 multiplied by a turns ratio.The turns ratio is the ratio of the number of turns in the main winding to the number of turns in a secondary winding. For example, if the number of turns in the main winding 12 is five and the number of turns in the secondary winding 14A is five, then the voltage across the secondary winding 14A is equal to the voltage across the main winding 12 (i.e., the turns ratio is 1:1). In the configuration illustrated in Figure 2, the turns ratio between the main winding 12 and each of the multiple secondary windings 14A-E is 1:1. For example, when the voltage across the main winding 12 is 20 volts, the voltages across each of the multiple secondary windings 14A-E are also 20 volts. When the multiple secondary windings 14A-E are connected in series, as illustrated in Figure 2, the voltage across the multiple secondary windings 14A-E is equal to the sum of the voltages across each of the secondary windings. For example, when the voltage across the main winding 12 is 20 volts, the voltage across the multiple secondary windings 14A-E is 100 volts (resulting from five secondary windings). The first and second 18A-B outputs provide connections between the multiple secondary windings 14A-E and one or more components external to housing 10. The voltage across the multiple secondary windings 14A-E is equal to the voltage difference between the first and second 18A-B outputs. For example, when the voltage across the multiple secondary windings 14A-E is 100 volts, the voltage difference between the first and second 18A-B outputs is 100 volts. Multiple electrical components 20 can be coupled to each of the multiple secondary windings 14A-E. These multiple electrical components 20 include, among others, a storage capacitor 22, a flyback diode 24, a capacitor filter 26, and a balance capacitor 28. In some embodiments, the multiple electrical components 20 are configured as illustrated in Figure 2 and described below. In some embodiments, the storage capacitor 22 and the capacitor filter 26 are coupled together in a parallel configuration. Additionally, in some embodiments, the flyback diode 24 is coupled in a series configuration with the storage capacitor 22 and the capacitor filter 26.Furthermore, in some forms, the series configuration of the return diode 24 and the storage capacitor 22 are coupled in a parallel configuration with the balance capacitor 28 and one of the multiple secondary windings 14A-E. The multiple electrical components 20 are located inside the amplifier housing 10, along with the main winding 12 and the multiple secondary windings 14A-E. This configuration allows for shorter cable trace lengths between the multiple electrical components 20 and each of the multiple secondary windings 14A-E compared to components located outside the amplifier housing 10. In addition to occupying less space for the signal amplifier 5, the shorter cable trace lengths reduce the effects of noise (e.g., switch noise) on the operation and efficiency of the signal amplifier 5. In this way, more accurate and stable electroporation signals can be produced with the portable equipment 100 in a much more compact portable unit 100. The configuration described above also allows for fewer outputs on the signal amplifier 5. If the multiple electrical components 20 were outside the amplifier housing 10, each secondary winding would require two outputs. For example, a signal amplifier with five secondary windings would require ten outputs. Placing the multiple electrical components 20 inside the amplifier housing 10, as illustrated in Figure 2, allows for the use of only two outputs (e.g., the first and second outputs 18A-B). Each additional output requires space and adds to the footprint of the signal amplifier. Therefore, by reducing the number of outputs, this configuration allows the signal amplifier 5 to have a smaller footprint and more efficient use of space on the corresponding circuit boards and within volume 120 of the housing 108. The flyback diode 24 is necessary to achieve a higher output voltage across the secondary winding 14A than the input voltage across the main winding 12. The voltage difference between the first and second inputs 16A-B induces a current in the main winding 12, creating a magnetic field. The secondary winding 14A picks up this magnetic field and creates a voltage / current spike. The energy from this voltage / current spike is stored in the storage capacitor 22 because the flyback diode 24 prevents the energy from leaking back into the secondary winding 14A. The energy stored in the storage capacitor 22 can only be discharged as a DC voltage output across the secondary winding 14A. The filter capacitor 26 suppresses voltage spikes across the secondary winding 14A that can occur when the voltage across the secondary winding changes suddenly.The balance capacitor 28 ensures that the voltage across each of the multiple secondary windings 14A-E is the same. Using the balance capacitor 28 eliminates the need for snubber circuitry in signal amplifier 5. The physical size of a capacitor is determined by two factors: working voltage and capacitance. Working voltage is the maximum voltage at which the capacitor can operate. The only way to increase a capacitor's working voltage is to increase its size. Capacitors with high working voltages are quite large. Capacitors with lower working voltages are smaller. Conventional high-voltage generators require capacitors with high working voltages. Therefore, conventional high-voltage generators tend to be larger. By generating multiple lower voltages and combining them in series to create a high voltage, Signal Amplifier 5 is smaller than conventional high-voltage generators because Signal Amplifier 5 does not require capacitors with high working voltages.These attributes are desirable in a portable device that must be held and maneuvered by the user during use. Capacitors with high operating voltages also require more time to fully charge and discharge. By generating multiple lower voltages and combining them in series to create a high voltage, the Signal Amplifier 5 provides high voltages significantly faster than conventional high-voltage generators. Furthermore, conventional high-voltage generators used in medical devices (e.g., electroporation pulse generators) that include capacitors with high operating voltages pose a risk of electrocution to medical device users. The capacitors in these high-voltage generators must be charged to high voltages before treatment begins and are capable of producing a high output voltage. During the time the capacitors are charging to high voltages but before the electroporation pulse is delivered, the capacitors hold a large amount of electrical energy. This large amount of electrical energy can seriously harm medical device users if they are electrocuted by the device. Additionally, the large amount of electrical energy can cause conventional high-voltage generators to explode.By generating multiple lower voltages and combining them in series to create a higher voltage, the Signal Amplifier 5 does not need to store a large amount of electrical energy. Therefore, the risk of electrocution present in conventional high-voltage generators is not present with the Signal Amplifier 5. In some embodiments, as illustrated in FIG. 1, the signal amplifier 5 includes a thermistor 30. The thermistor is a type of resistor whose resistance depends on the temperature. In some embodiments, a very short duty cycle is used with the signal amplifier. This short duty cycle may be greater than the DC capability of the signal amplifier 5. A control circuit (not shown) may be used to ensure that the signal amplifier 5 does not exceed the capabilities of the components by controlling the thermistor 30. In some embodiments, as illustrated in FIG. 1, the thermistor 30 is coupled between a common node connected to the multiple secondary windings 14A-E and the main winding 12. Power Supply 34 supplies a nominal or pulsed DC voltage to Voltage Amplifier 5. In the illustrated configuration, Power Supply 34 is powered by one or more batteries or battery packs. In other configurations, Power Supply 34 is powered from the mains with nominal line voltages between, for example, 100V and 240V AC and frequencies of approximately 50-60 Hz. In still other configurations, Power Supply 34 is powered by a combination of battery and mains power. In some configurations, Power Supply 34 is powered by USB (i.e., Universal Serial Bus) which has a nominal line voltage of 5V. In some configurations, the batteries are rechargeable. Rechargeable batteries include, for example, lithium-ion, lead-acid, nickel-cadmium, nickel-metal hydride, etc. Lithium-ion batteries are smaller and lighter than conventional lead-acid batteries. Power switch 36 regulates the flow of power from power supply 34 to signal amplifier 5. The power switch is electrically coupled to signal amplifier 5 through the first and second inputs 16A-B. The voltage difference between the first and second inputs 16A-B is based on the ON time compared to the OFF time (i.e., the duty cycle) of power switch 36. In some configurations, power switch 36 includes an interrupting field-effect transistor (FET). Therefore, the description provides, among other things, a signal amplifier and a signal generator. Several features and advantages of the description are set forth in the following claims. In order to provide integrity, several aspects of the invention are set forth in the following numbered clauses: Clause 1. A portable unit for use in an electroporation device, the portable unit comprising: accommodation; A signal amplifier located inside the housing; the signal amplifier includes: a main winding, multiple secondary windings coupled in a series configuration, where a storage capacitor and a flyback diode are coupled to each of the multiple secondary windings; and an assembly having multiple electrodes in electrical communication with the signal amplifier. Clause 2. The portable equipment of clause 1, wherein the turns ratio between the main winding and each of the multiple secondary windings is one to one. Clause 3. The portable equipment of clause 1, wherein each flyback diode and storage capacitor is coupled to one of the respective multiple secondary windings in a series configuration. Clause 4. The portable equipment of clause 1, wherein the flyback diode and storage capacitor are coupled to each of the multiple secondary windings in parallel configuration. Clause 5. The portable equipment of clause 4, wherein a capacitor filter is coupled in a parallel configuration with the storage capacitor. Clause 6. The portable equipment of clause 5, wherein a balance capacitor is coupled to each of the multiple secondary windings in parallel configuration. Clause 7. The portable equipment of clause 6, where a thermistor is coupled between the multiple secondary windings and the main winding. Clause 8. The portable equipment of clause 1, where the multiple secondary windings include at least five secondary windings. Clause 9. The portable equipment of clause 1, where the main winding, the multiple secondary windings, the storage capacitor and the flyback diode are MA / a / ZUZ^ / UU / U 14 placed inside a signal generator housing. Clause 10. An electroporation device comprising: accommodation; a signal generator located inside the housing that includes: a signal amplifier having a main winding and multiple secondary windings coupled together in a series configuration, wherein a storage capacitor and a flyback diode are coupled to each of the multiple secondary windings; a power supply, and a power switch configured to supply a voltage from a power supply through the main winding; and an assembly having one or more electrodes in electrical communication with the signal generator. Clause 11. The electroporation device of clause 10, wherein the turns ratio between the main winding and each of the multiple secondary windings is one to one. Clause 12. The electroporation device of clause 10, wherein the power supply includes a rechargeable battery. Clause 13. The electroporation device of clause 12, wherein the rechargeable battery includes a lithium-ion battery. Clause 14. The electroporation device of clause 10, wherein the flyback diode and the storage capacitor are coupled together in a series configuration. Clause 15. The electroporation device of clause 14, wherein the flyback diode and storage capacitor are coupled to each of the multiple secondary windings in a parallel configuration. Clause 16. The electroporation device of clause 15, wherein the capacitor filter is coupled in a parallel configuration with the storage capacitor. Clause 17. The electroporation device of clause 10, wherein a balance capacitor is coupled to each of the multiple secondary windings in parallel configuration. Clause 18. The electroporation device of clause 10, wherein a thermistor is coupled between the multiple secondary windings and the main winding. Clause 19. An electroporation system comprising: a base station; and a portable device removably attached to the base station, the portable device including: accommodation; an injection assembly, a power supply, and a signal generator located within the portable equipment housing and in operational communication with the injection assembly, the signal generator comprising: A signal amplifier having a main winding, and multiple secondary windings coupled together in a series configuration, wherein a storage capacitor and a flyback diode are coupled to each of the multiple secondary windings and a power switch configured to supply a voltage from the power supply through the main winding and an assembly having at least one electrode extending therefrom and in electrical communication with the signal generator. Clause 20. The electroporation system of clause 19, wherein the base station is in electrical communication with the power supply when the base station is coupled to the portable equipment.

Claims

1. An electroporation device comprising: an assembly having one or more electrodes, the assembly coupled to a housing; a signal generator placed within the housing; the signal generator including: a power supply; a signal amplifier having a main winding and multiple secondary windings; and a first input and a second input providing electrical communication between the power supply and the main winding; wherein the multiple secondary windings are coupled together in a series configuration, and the multiple secondary windings comprise a first output and a second output in electrical communication with the assembly, such that a voltage across the multiple secondary windings is equal to the voltage difference between the first and second outputs.

2. The electroporation device according to claim 1, further characterized in that a voltage difference between the first and second inputs is equal to a voltage across the main winding.

3. The electroporation device according to claim 1, further characterized in that it additionally comprises a power switch configured to supply a voltage from the power supply to the first and second inputs. 4 - The electroporation device according to claim 1, further characterized in that each of the multiple secondary windings is coupled to a respective storage capacitor and a respective return diode. 5 - The electroporation device according to claim 4, further characterized in that the turns ratio between the main winding and each of the multiple secondary windings is one to one.

6. The electroporation device according to claim 4, further characterized in that each respective return diode and each respective storage capacitor are coupled to the respective one of the multiple secondary windings in a series configuration.

7. The electroporation device according to claim 4, further characterized in that the respective return diode and the respective storage capacitor are coupled to the respective one of the multiple secondary windings in a parallel configuration.

8. The electroporation device according to claim 7, further characterized in that the respective storage capacitor and a respective capacitor filter are coupled together in a parallel configuration.

9. The electroporation device according to claim 8, further characterized in that each of the multiple secondary windings is coupled to a respective balance capacitor in a parallel configuration.

10. The electroporation device according to claim 9, further characterized in that a thermistor is coupled between the multiple secondary windings and the main winding.

11. The electroporation device according to claim 1, further characterized in that the multiple secondary windings include at least five secondary windings.

12. The electroporation device according to claim 1, further characterized in that the main winding, the multiple secondary windings, the storage capacitors and the flyback diodes are each arranged within a signal generator housing. 13.- A signal amplifier for an electroporation device, comprising: a first input and a second input; a main winding in electrical communication with the first and second inputs; multiple secondary windings in electromagnetic communication with the main winding, wherein the multiple secondary windings are coupled together in a series configuration, wherein the multiple secondary windings comprise a first output and a second output, such that a voltage across the multiple secondary windings is equal to the voltage difference between the first and second outputs. 14.- The signal amplifier according to claim 13, further characterized in that a voltage difference between the first and second inputs is equal to a voltage across the main winding.

15. The signal amplifier according to claim 13, further characterized in that the main winding and the multiple secondary windings are placed inside an amplifier housing.

16. The signal amplifier according to claim 13, further characterized in that each of the multiple secondary windings is coupled to a respective storage capacitor and a respective flyback diode.

17. The signal amplifier according to claim 16, further characterized in that the turns ratio between the main winding and each of the multiple secondary windings is one to one.

18. The signal amplifier according to claim 16, further characterized in that each respective return diode and the respective storage capacitor are coupled to the respective one of the multiple secondary windings in a series configuration.

19. The signal amplifier according to claim 16, further characterized in that the respective return diode and the respective storage capacitor are coupled to the respective one of the multiple secondary windings in a parallel configuration.

20. The signal amplifier according to claim 19, further characterized in that the respective storage capacitor and a respective capacitor filter are coupled together in a parallel configuration.

21. The signal amplifier according to claim 20, further characterized in that each of the multiple secondary windings is coupled to a respective balance capacitor in a parallel configuration.

22. The signal amplifier according to claim 21, further characterized in that a thermistor is coupled between the multiple secondary windings and the main winding.

23. The signal amplifier according to claim 13, further characterized in that the multiple secondary windings include at least five secondary windings.

Images