Method and system for applying a pulsed electric field with high uniformity using a magnetic core

Abstract

An apparatus, system and method for generating a pulsed electric field with good uniformity is provided. The electric field occupies a large volume suitable for placement of a human or animal patient. An apparatus for generating an electric field is provided, the apparatus comprising one or more toroidal or cylindrical magnetic cores wrapped with wires that, when pulsed with an electric current, generate a highly uniform electric field in the interior region of the toroidal or cylindrical core. These electric field pulses, when used in combination with pharmacological agents, destroy cancer cells through a process known as targeted osmotic lysis.

Description

[0001] Related Applications

[0002] This application claims priority to U.S. Provisional Application No. 62 / 776,105, filed on December 6, 2018, and U.S. Provisional Application No. 62 / 942,348, filed on December 2, 2019, both of which are incorporated herein by reference in their entirety for all purposes.

[0003] field

[0004] The present invention relates to the field of medical devices and medical treatment of diseases and disorders. More specifically, the present invention relates to methods and systems for applying pulsed electric fields with high uniformity using an annular or cylindrical magnetic core for medical applications. Background Art

[0005] Pulsed electric field therapy is now widely used in a variety of biological and medical applications: gene delivery, electrochemotherapy and cancer therapy. One advantage of pulsed electric field therapy is the ability to destroy tissue or tumors in a non-thermal way. Therefore, pulsed electric field therapy makes it possible to keep sensitive tissues such as blood vessels and axons intact. In addition, this non-invasive technology allows the possibility of regeneration with healthy cells and tissue in the treatment area without leaving scars, and unlike electrical current stimulation, the delivery of stimulation is significantly more uniform.

[0006] Conventional devices consist of three parts: a pulse generator, electrodes, and the connecting link between them. The pulse generator generates square wave pulses at regular intervals. Amplitude, pulse width, period, and phase delay are the main parameters that determine the shape of the output waveform. Depending on the pulse amplitude and the distance between the electrodes, the electric field strength is often critical for a complete therapeutic effect. When the electrodes are not suitable, the intensity is insufficient in a certain target area, resulting in an incomplete therapeutic effect.

[0007] The electric field is generated by equipment similar to that used in radar. This has some implications for cost and availability. The most typical equipment generates a short square wave and reverses the polarity, partly to avoid corrosion of the electrodes. However, a bipolar generator costs about twice as much as a monopolar generator. Other waveforms include exponentially decaying and sinusoidal waveforms. The sinusoidal form is somewhat easier to generate because it uses equipment similar to that of ordinary radio equipment, but it reaches peak power only for a moment and therefore delivers less energy per cycle above a critical field strength than a square wave.

[0008] Two alternatives for generating such electric field pulses are obvious. The first is to use a solenoid arrangement, such as a large coil that generates a uniform magnetic field inside. The patient will be placed inside the solenoid. However, this technology has great disadvantages. The first is that the generated electric field is zero along the axis of such a solenoid and increases linearly with the distance from the central axis. Therefore, the electric field not only disappears in the most critical area, but is also highly non-uniform everywhere. In fact, this non-uniformity is an inherent limitation of any technology that places a patient in an area of ​​a ramped magnetic field. Due to the physical properties of electromagnetic fields, the electric field in the area of ​​a changing magnetic field must be non-uniform. The second disadvantage of such technology is the amount of heat that such coils will generate. If such coils are designed to be large enough so that human patients or medium-sized animals fit inside, the coils will generate a very large amount of heat, which must not only be removed from the device, but also impose a large number of HVAC requirements on the building where the device is applied. For devices that are scaled up to be applied to human or large animal sizes, peak thermal power in the range of 50-400 kilowatts will be generated. Such power requirements pose a huge challenge to building facilities.

[0009] A second alternative for generating an electric field is to use an arrangement of charged objects, such as conductive plates, to generate the electric field. A disadvantage of this technique is that the most practical implementation involves applying the electric field in such a way that the field points are arranged perpendicular to the surface of the patient, resulting in a substantial reduction in the electric field within the patient due to the dielectric polarization of water molecules within the tissue. In addition, the actual field is very sensitive to the percentage of space between the plates filled by the patient. Another disadvantage of this technique is the sensitivity to the geometry of the patient. Patients with larger waists require different applied voltages. Different areas of the body with different sizes (such as arms and legs compared to the torso) will receive very different electric field doses. The plates can be placed in direct contact with the patient, but unless the plates are flexible, they will only contact a portion of the patient's skin. In this way, a large amount of energy is required to overcome the impedance of the skin, and electrical stimulation is uncomfortable and often painful. Such limitations are practical in nature, and it is believed that the methods disclosed herein provide many advantages for such methods.

[0010] Despite recent advances in the use of electrical pulses to induce cell death, there remains a need in the art for improved methods to destroy diseased or disordered tissue, such as tumor tissue, without damaging normal tissue. In particular, there is a need for methods and systems for generating large volumes of pulsed electric fields with high uniformity. SUMMARY OF THE INVENTION

[0012] In view of the foregoing, it is an object of the present invention to address the need to generate large volumes of pulsed electric fields with high uniformity for medical applications. Embodiments of the present invention relate to methods and systems for generating pulsed electric fields in empty space with amplitudes in the range of 0-100 volts / meter and durations in the range of 1-50 milliseconds each. The electric field occupies a large volume suitable for placement of a human or animal patient. The electric field has good uniformity.

[0013] One embodiment provides a device for generating a pulsed electric field, the device comprising a plurality of toroidal magnetic cores wrapped with wires. Another embodiment provides a device for generating an electric field, the device comprising a plurality of magnetic cores formed in a cylindrical geometry, such that the magnetic material occupies an annular region around the axis of the cylinder, and the central region of the cylinder is empty. Various designs include cores similar to long cylinders and short cores similar to toroidal geometries. The magnetic cores are wrapped with wires that, when pulsed with an electric current, generate a highly uniform electric field in the interior region of the toroidal or cylindrical core. These electric field pulses, when used in conjunction with pharmacological agents, destroy cancer cells through a process known as targeted permeation lysis (TOL). See US8,921,320.

[0014] The magnetic core is constructed of a material with high magnetic permeability. When current is applied to the electrical windings, a large magnetic field is generated inside the magnetic material. The field is most uniform along the axis of the toroidal or cylindrical core near the center of the device. Application of a time-dependent current results in a changing magnetic field inside the core, which in turn generates an electric field outside the core material that can be used for therapeutic purposes. The amplitude, duration, and time interval of the electric field pulses can be controlled by controlling the voltage and current applied to the electrical windings.

[0015] Important properties of the generated electric field are high uniformity and direction along the long axis of the human subject or many animal subjects. Another important aspect of the device is that it produces the electric field with very low power generated, allowing for low cost drive electronics, low electrical requirements for the facility, and no impact on the HVAC system of the clinical facility.

[0016] The annular or cylindrical cores are coaxially arranged at intervals that optimize the uniformity of the generated electric field. The generated electric field is directed in an axial direction along the annular or cylindrical core. The patient is placed in an inner region along the axis of the annular or cylindrical core.

[0017] The system consists of a donut-shaped or cylindrical device connected to a set of drive electronics that allow the user to control the amplitude, duration, and spacing of the electric field pulses. The electronics consist of components that generate the pulsed voltage or current waveform, components that amplify and filter the output of the waveform, and a microprocessor that provides a user interface for controlling the output.

[0018] Specifically, an embodiment provides a device for generating a pulsed electric field, comprising:

[0019] one or more annular or cylindrical structures,

[0020] a plurality of conductive windings wound around each annular or cylindrical structure, and

[0021] A plurality of wires that supply electric current to a conductive winding.

[0022] According to one embodiment, the annular structure is made of a magnetic material with a high relative permeability in the range of 1,000 to 40,000. Magnetic materials with a permeability of 40,000 or more can be used for this application. Some examples of suitable magnetic materials include, but are not limited to, silicon steel, iron powder, nickel-iron alloys, ferrite ceramics, nanocrystalline alloys of iron, boron and silicon. The conductive winding is made of copper wire in the range of 10-28AWG and is wound on the annular structure into a coil arrangement of typically 1 to 200 turns. Other examples of suitable materials for the conductive winding include, but are not limited to, aluminum, silver, tin, galvanized steel, phosphor bronze, lead and gold. When the current passing through the conductive winding is inclined, a magnetic field is generated inside the magnetic material.

[0023] According to one embodiment, a plurality of annular structures are coaxially aligned and spaced apart by a distance equal to the radius of the annular structures. In at least another embodiment, three annular structures are axially arranged with one annular structure having a larger radius being located midway between two identical annular structures.

[0024] According to another embodiment, the cylindrical structure is made of a magnetic material with a high relative magnetic permeability, which is typically greater than 1,000. Some examples of suitable magnetic materials include, but are not limited to, silicon steel, iron powder, nickel-iron alloys, ferrite ceramics, nanocrystalline alloys of iron, boron, and silicon. The conductive winding is made of copper wire in the range of 10-28AWG and is wound on the cylindrical structure into a coil arrangement of typically 1 to 200 turns. Other examples of suitable materials for the conductive winding include, but are not limited to, aluminum, silver, tin, galvanized steel, phosphor bronze, lead, and gold. When the current passing through the conductive winding is oblique, a magnetic field is generated inside the magnetic material.

[0025] According to another embodiment, a plurality of cylindrical structures are coaxially aligned. The spacing between the cylindrical structures and the current flowing through the coil surrounding each cylindrical structure are adjusted to provide optimal electric field strength and uniformity, as well as having desired electrical characteristics, such as inductance and resistance.

[0026] According to at least one embodiment, an apparatus for generating a pulsed electric field further comprises an additional coil winding for sensing an electric field generated within the apparatus. The additional coil winding comprises a loop of wire that surrounds a cross-section of an annular or cylindrical structure by at least one turn or more turns to have a higher sensitivity to the electric field, wherein the loop of wire induces a voltage that is proportional in magnitude to the rate of change of magnetic flux through the cross-section of the annular or cylindrical structure.

[0027] Another embodiment is directed to a system for therapeutic treatment involving electric fields, comprising:

[0028] annular or cylindrical device for generating a pulsed electric field,

[0029] Drive and sensing circuitry,

[0030] a plurality of cables connecting the device to the drive and sensing circuitry, and

[0031] A microprocessor provides a user interface for operating the device as well as the drive and sensing circuitry.

[0032] According to one embodiment, the magnetic annular or cylindrical device comprises one or more annular or cylindrical structures, conductive windings wrapped around the annular or cylindrical structures, and wires supplying current to the conductive windings. When combined with pharmacological agents, pulsed electric fields are used in applications for targeted osmotic lysis for treating cancer.

[0033] Further embodiments are directed to a method for therapeutic treatment involving electric fields, comprising generating a pulsed electric field by a magnetic annular or cylindrical device, wherein the magnetic annular or cylindrical device comprises one or more magnetic annular or cylindrical structures, conductive windings wound around the annular structures, and wires supplying current to the conductive windings. When combined with a pharmacological agent, the method can be used in applications of targeted osmotic lysis for treating cancer. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] The invention will be described in more detail below based on one or more figures, which show exemplary embodiments.

[0036] Figure 1 A single toroidal coil with windings is depicted. The toroidal coil is composed of a magnetic material with high magnetic permeability, an example of which is silicon steel.

[0037] Figure 2 A single cylinder with windings is depicted. The cylinder is composed of a magnetic material with high magnetic permeability, an example of which is silicon steel.

[0038] Figure 3.A ring-shaped or cylindrical structure having a magnetic structure that is closed except for a gap that is wide enough to accommodate the relevant anatomical structure.

[0039] Figure 4 The two toroidal cores are arranged in such a way that an electric field is generated in the empty area inside the toroidal cores.

[0040] Figure 5 .Multiple cylinders are coaxially arranged to provide an extended area of ​​electric field exposure.

[0041] Figure 6 .A wire loop that can be looped around a circular cross section once or more than once to provide a higher sensitivity to electric fields.

[0042] Figure 7 .Therapeutic system comprising an annular or cylindrical core in a housing and connected to a control system for application of therapy involving electric fields.

[0043] Figure 8 .Typical pulse sequences associated with TOL applications.

[0044] Fig. 9 Mice treated with Tol took significantly longer to reach humane euthanasia criteria than mice in the control group. Arrows indicate treatment days.

[0045] Detailed description of embodiments

[0046] It should be understood that the present invention is not limited to the specific methods, schemes, systems, etc. described herein and may vary accordingly. The terminology used herein is only for the purpose of describing specific embodiments and is not intended to limit the scope of the present invention, which is limited only by the claims.

[0047] As used in the specification and the appended claims, unless indicated to the contrary, the following terms have the meanings indicated below.

[0048] "Relative permeability" refers to the ratio of the magnetic permeability of a particular medium to the magnetic permeability of free space.

[0049] The terms used herein are for the purpose of describing specific embodiments only and are not intended to limit the present invention. As used herein, the singular forms "a", "an" and "the" are also intended to include the plural forms, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" and / or "comprising", when used in this specification, specify the presence of the features, integers, steps, operations, elements and / or components, but do not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components and / or groups thereof.

[0050] The following description and accompanying drawings fully illustrate specific embodiments to enable those skilled in the art to practice them. Other embodiments may incorporate structural, logical, electrical, process and other changes. Parts and features of some embodiments may be included in or replaced by those parts and features of other embodiments.

[0051] The present invention addresses the need to generate pulsed electric fields in large (human-sized) volumes. This need arises in the application of targeted osmotic lysis (TOL), which uses such electric field pulses to stimulate sodium channels in the cell membrane of cancer cells to open. See US8,921,320. It is desirable that the electric field be highly uniform so that the associated therapeutic effect is uniform.

[0052] The technique involves the use of a tilted magnetic field confined in a high permeability material, such as a transformer core. The preferred embodiment is a toroidal or cylindrical core shape with an inner diameter large enough to place the patient through the interior, as well as other components of the device, such as patient handling hardware.

[0053] The electric field is Figure 1 The toroidal device shown in is produced. The toroidal device consists of an annular structure 1 and a conductive winding 2, the annular structure 1 is made of a material with high magnetic permeability, such as silicon steel or other materials commonly used in the core of power transformers, the conductive winding 2 is wound around the annular material, and the current is supplied through the wire 3. The magnetic material of the annular shape usually has a relative magnetic permeability in the range of 1,000-40,000. It is hoped that the magnetic permeability is as large as possible. Some other materials that can be considered suitable are, for example, iron powder, nickel-iron alloy, ferrite ceramics, and nanocrystalline alloys of iron, boron and silicon. The conductive winding is usually a copper wire in the range of 10-28AWG, which is wound on the annular coil into a coil arrangement usually having 1-200 turns, depending on other aspects of the drive circuit system.

[0054] like Figure 1 As shown in FIG. 1 , a toroidal coil 1 is tightly wound with a coil of current-carrying wire 2 in a manner similar to a transformer. The toroidal coil comprises a high permeability magnetic material. Examples of magnetic materials include, but are not limited to, silicon steel. The current passing through these wires is inclined, thereby generating a strong magnetic field inside the magnetic material. This magnetic field increases or decreases as the current in the wire increases or decreases, which creates an associated electric field through the Faraday effect. By changing the magnitude of the magnetic field over time, as Figure 1 As shown, an electric field is generated in a region defined by the inner region of the toroidal core.

[0055] Due to the high magnetic permeability of the toroidal coil material, the current in the windings 2 generates a strong magnetic field inside the toroidal coil. If the current in these windings changes over time, the changing current will generate a changing magnetic field inside the toroidal coil. This changing magnetic field generates an electric field through Faraday's law of induction inside the toroidal coil material but also in the area outside the toroidal coil material (including the central area 4 of the toroidal coil). The size of the generated electric field is proportional to the rate of change of the magnetic field inside the toroidal coil material.

[0056] Figure 1 The toroidal cell 1 in the embodiment can in principle be shaped into non-circular geometries and need not be a completely closed structure. Circular shapes and closed structures are preferred embodiments because they produce a highly uniform field with a low power input. For non-closed shapes, such as a toroid with gaps, the required input power will increase, but the power requirement will still be significantly reduced relative to not using magnetic material. If it is desired that the electric field pulse only spread over a small volume, the field can be created by having a magnetic structure that is closed except for a gap that is wide enough to place the relevant anatomical structure, such as Figure 3 as shown in .

[0057] The electric field is generated by a cylindrical device, e.g. Figure 2 As shown in . The device consists of a cylindrical structure 1, which is made of a material with high magnetic permeability, such as silicon steel or other materials commonly used in the core of power transformers, and a conductive winding 2, which is wound around the cylindrical material and supplied with current through an electric wire 3. The magnetic material of the cylinder usually has a relative magnetic permeability higher than 1,000. It is desirable that the magnetic permeability is as large as possible. Some other materials that may be considered suitable are, for example, iron powder, nickel-iron alloys, ferrite ceramics, and nanocrystalline alloys of iron, boron and silicon. The conductive winding is usually copper wire in the range of 10-28AWG, wound on the cylinder into a coil arrangement typically having 1-200 turns, depending on other aspects of the drive circuit system.

[0058] like Figure 2 As shown in FIG. 1 , a cylinder 1 is tightly wound with coils of current carrying wire 2 in a manner similar to a transformer. The cylinder comprises a high permeability magnetic material. Examples of magnetic materials include, but are not limited to, silicon steel. The current passing through these wires is inclined, thereby generating a strong magnetic field inside the magnetic material. This magnetic field increases or decreases as the current in the wires increases or decreases, which generates an associated electric field through the Faraday effect. By varying the magnitude of the magnetic field over time, an electric field is generated in an area defined by the interior area of ​​the cylinder, as shown in FIG. Figure 2 shown.

[0059] Due to the high magnetic permeability of the magnetic material constituting the cylinder, the current in the windings 2 generates a strong magnetic field inside the cylinder. If the current in these windings varies with time, the varying current generates a varying magnetic field inside the cylinder. This varying magnetic field generates an electric field via Faraday's law of induction within the magnetic cylindrical material but also in the area outside the cylindrical material, including the central area 4 of the cylinder. The magnitude of the generated electric field is proportional to the rate of change of the magnetic field inside the cylindrical material.

[0060] Figure 2 The cylindrical cell 1 in the embodiment can in principle be shaped into non-circular geometries and need not be a completely closed structure. Circular shapes and closed structures are preferred embodiments because they produce a highly uniform field with a low power input. For non-closed shapes, such as a cylinder with gaps, the required input power will increase, but the power requirement will still be significantly reduced compared to not using magnetic material. If it is desired that the electric field pulse only spread over a small volume, the field can be created by having a magnetic structure that is closed except for the gaps that are wide enough to place the relevant anatomical structure, such as Figure 3 as shown in .

[0061] By using multiple such annular or cylindrical cores with a carefully designed geometric relationship regarding diameter and spacing, a large area of ​​high electric field uniformity can be generated. One embodiment is similar to the Helmholtz Coil used to generate a magnetic field from an electric current. In this arrangement, as Figure 4 As shown in , the toroidal cores are aligned so they share a common axis and are spaced a distance equal to the radius of the toroidal or cylindrical core. Figure 5 Another embodiment is shown in , where multiple cylindrical cores are arranged to share a common axis. Figure 4 and Figure 5 In either of the configurations depicted in , the patient is placed along the central axis of the device. When so arranged, the electric field runs along the axis of the annular or cylindrical core, which in preferred applications will run along the long axis of a human patient or many types of veterinary patients. Such an arrangement maximizes the uniformity of the electric field of the two coils. A larger uniform area can be produced by using more than two coils. For example, with three coils, an arrangement similar to Maxwell coils for magnetic fields can be used, which includes a coil with a larger radius located in the middle of two identical coils. Such a design can be extended to an arbitrarily large number of coils to increase the uniform volume at the expense of system cost, weight, and complexity.

[0062] To obtain an electric field pulse of a given amplitude, the coil is driven by a voltage pulse. The voltage applied across the coil windings generates an electric field around the coil, inducing an opposing voltage in the windings, just as occurs in any inductor. The electric field that produces this opposing voltage is the desired electric field. Although some of the applied voltage is consumed in the resistance of the windings and other components in the circuit, the main part is responsible for generating the desired electric field. There are three main benefits to generating the electric field using this method. First, the electric field has high spatial uniformity. Second, the electric field is directed tangentially to the surface of the patient lying in the device. Third, the power requirements and heat generation are very low relative to some other methods. High uniformity is required so that treatment is applied in a consistent manner throughout the body or treatment area. The usable treatment area for this application is considered to be where the field intensity varies less than about 10% in empty space.

[0063] The desirability of directing the electric field tangentially to the patient's surface is to minimize the reduction in the electric field that occurs due to polarization of water molecules inside the body. Water has a strong polarizability (electric susceptibility), which can cause a significant reduction in the field inside the body. The effect is greatest for fields directed perpendicular to the surface, where the electric field is reduced by as much as a factor of 75-80. For electric fields directed along the patient's surface, the reduction can be much smaller, ranging from almost no reduction to a reduction of about 1 / 20.

[0064] The technology has very low power requirements due to the use of materials with high magnetic susceptibility in the toroidal or cylindrical core. Without the use of magnetic materials, the power required and the heat generated can be more than 10,000 times higher, resulting in arduous electrical requirements, engineering challenges related to heat removal, patient safety issues, and onerous special requirements for building HVAC systems.

[0065] Such power estimates can be made by considering the current density required to produce the desired magnetic field using a cylindrical geometry. A useful reference geometry for such comparisons is that the current occupies a cylindrical ring in space, from radius R1 to radius R2, of length L, flowing primarily in the azimuthal direction. One skilled in the art can easily calculate the current density required to produce a given magnetic field oriented along the axis of the solenoid, and estimate the resulting heat density using the electrical conductivity of copper. For example, using solid copper to fill a cylindrical ring with an inner diameter of 70 cm and an outer diameter of 110 cm, 1 meter long, would result in a peak heat generation of over 40 kilowatts, and would require over 2000 pounds of copper.

[0066] The peak power required to generate similar electric fields in the devices described in this disclosure is in the range of 5-20 Watts when using high permeability materials (such as silicon steel) in the toroidal coils, and is typically less than 100 Watts when using high permeability materials (such as silicon steel) in the cylinders. This large reduction in power is a result of the very high permeability of the magnetic material, resulting in a magnetic field inside the magnetic material that is approximately four orders of magnitude larger than the magnetic field in empty space for the same winding pattern.

[0067] The electric field amplitude can be controlled in an "open loop" arrangement, where the expected electric field output is known from the input voltage, the generated current, and the system resistance; or it can be controlled in a "closed loop" arrangement, where a feedback loop is used. The electric field can be measured in the manner described below, and this information is fed back to the electronic system in a feedback loop, which adjusts the applied voltage to produce the desired electric field amplitude.

[0068] The measurement of the electric field is done through a combination of calculations and measurements. Measuring the local electric field can be very difficult, but it is possible to perform an overall measurement around a closed loop. Figure 6 The wire loop 5 shown encircling the cross section of the toroid or cylinder will induce a voltage therein which is equal in magnitude to the rate of change of magnetic flux through the toroid / cylinder cross section, since nearly all of the magnetic flux is contained within the magnetic material. The overall voltage will depend only on the number of times the wire wraps around the cross section, and is otherwise independent of the path followed by the loop.

[0069] The spatial correlation of the electric field can be calculated from the known geometry and related to the voltage measured around a single wire loop. To perform the voltage measurement around a wire loop, a wire loop is passed around the cross section of a toroidal coil or cylinder and closed at a high impedance terminal (such as the input of an oscilloscope or any high input impedance terminal). As long as the input impedance of the terminal is much larger than the resistance of the wire, almost the entire voltage induced around the wire loop will be dropped at the high impedance terminal. The voltage around the wire loop can be used together with the calculated spatial distribution of the electric field to obtain a local value of the electric field strength. In this capacity, the voltage induced around a single wire loop acts as a scaling or calibration factor for the spatial distribution.

[0070] Therefore, an additional element of the device is a wire loop 5 which may be wrapped around the toroidal coil or cylindrical cross section once or more than once for greater sensitivity to the electric field. This wire is connected back to the system electronics for monitoring the electric field, or for the feedback loop described previously.

[0071] The voltage pulses in the drive electronics can be generated using many different types of amplifier configurations. Since the voltages required to drive the toroidal or cylindrical windings are usually in the 15-100 volt range, a Class D amplifier configuration is required to avoid large amounts of heat dissipation in the amplifier's output transistors. This configuration uses pulse width modulation (PWM) to control the amplifier's output and is known for high efficiency and low cost.

[0072] Devices that generate electric fields can be further incorporated into the system, which can be used in a therapeutic capacity and, when combined with pharmacological agents, can treat certain types of cancer, such as Figure 7 Specifically, the system includes one or more annular or cylindrical cores in a housing and connected to a control system for application of therapy involving electric fields. Figure 7 A block diagram of the system is shown. An annular or cylindrical device 6 generates electric field pulses in the internal area where the patient is placed. Cables 7 connect the annular or cylindrical device to drive and sense circuitry 8.1-8.3, which provides voltage or current pulses to windings on the annular unit. Sensing coils within the annular or cylindrical unit measure the electric field generated within the annular or cylindrical unit and can be used to control the output. A microprocessor 9 provides a user interface to the operator of the device and interfaces with the drive and sense circuitry to control the amplitude, duration and spacing of the pulses, as well as to start and stop the pulses.

[0073] The drive electronics are connected to a computer that hosts a user interface that enables the user to control pulse amplitude, duration, and interval, as well as start and stop pulse therapy. The computer can communicate with the drive electronics via a serial bus, but other options are possible.

[0074] Pulsed electric field systems can be applied to a therapeutic technique called targeted osmotic lysis (TOL). See US8,921,320. The principle behind this technology is that electric field pulses stimulate sodium channels in the cell membrane to open, transporting more sodium into the cell. It is well known that cancer cells have many more sodium channels than non-cancerous cells. An increase in intracellular sodium concentration is produced. Pharmacological agents prevent sodium from being discharged from the cell. The result is an increase in intracellular osmotic pressure, causing the cell to rupture. Since cancer cells have many more sodium channels than non-cancerous cells, normal tissue is preserved.

[0075] Figure 8A typical pulse sequence associated with TOL applications is shown. In free space, the electric field amplitude falls within the range of 0.1 V / m to 100 V / m. The pulse consists of a forward polarization of approximately 1-50 milliseconds, followed by a reverse polarization of similar duration and amplitude. The pulse is separated from the end to the beginning by 5-50 milliseconds. The exact details of the timing, duration, and amplitude may vary in the application.

[0076] Fig. 9 An in vivo validation of the therapeutic efficacy of a pulsed magnetic field inducing osmotic lysis in a breast cancer mouse model is described. Four groups of female immunocompetent BALBc mice (n=8) with xenografts (0.7-1.2 cm in diameter on the lower back) were established after five injections of 7 mg / kg digoxin or 500K highly malignant mouse breast cancer 4T1 cells in saline (subcutaneous back of the neck) at 1 hour intervals. This regimen established steady-state pharmacokinetics even in poorly vascularized tissues. Starting 15 minutes after the last injection, the mice were exposed to a pulsed magnetic field generated by a ring-shaped device for 30 minutes. The treatment was performed on day 0 (the first day of treatment) and day 1. The mice were monitored for tumor growth and were killed when they met the NIH humane endpoint euthanasia criteria. As Fig. 9 As shown in , the time to humane euthanasia for mice treated with TOL was significantly longer than that for mice in the control group.

[0077] The electric fields generated by the toroidal or cylindrical devices may also have other therapeutic or industrial applications.

[0078] It should be understood that the above embodiments are only illustrations of numerous and different other embodiments that can constitute the application of the principles of the present invention. Without departing from the spirit or scope of the present invention, those skilled in the art can easily design such other embodiments, and our intention is to regard them as within the scope of the present invention.

[0079] Aspects of the present disclosure may be implemented in one or more of the following embodiments.

[0080] 1) A device for generating a pulsed electric field, comprising:

[0081] One or more annular or cylindrical structures 1,

[0082] a plurality of conductive windings 2 wound around each annular or cylindrical structure, and

[0083] A plurality of electric wires 3 supply electric current to the conductive winding 2 .

[0084] 2) The device according to 1), wherein the annular or cylindrical structure 1 is made of a magnetic material with high relative magnetic permeability.

[0085] 3) The device according to 2), wherein the relative magnetic permeability of the magnetic material is 1,000 or more.

[0086] 4) The device according to 2), wherein the magnetic material is selected from the group consisting of silicon steel, iron powder, nickel-iron alloy, ferrite ceramic, nanocrystalline alloy of iron, boron and silicon.

[0087] 5) The device according to 1), wherein the conductive winding 2 is made of a material selected from the group consisting of aluminum, silver, tin, galvanized steel, phosphor bronze, lead or gold.

[0088] 6) The device according to 1), wherein the conductive winding 2 is made of copper wire in the range of 10-28 AWG.

[0089] 7) The device according to 1), wherein the conductive winding 2 is wound on the annular or cylindrical structure into a coil arrangement of 1 to 200 turns.

[0090] 8) The device according to 1), wherein when the current passing through the conductive winding 2 is inclined, a magnetic field is generated in the magnetic material.

[0091] 9) The device according to 8), wherein the magnetic field increases or decreases as the current in the conductive winding 2 increases or decreases to generate the pulsed electric field.

[0092] 10) The device according to 9), wherein the pulsed electric field is generated in the inner region of the annular or cylindrical structure 1 by changing the magnitude of the magnetic field over time.

[0093] 11) The device according to 10), wherein the magnitude of the generated pulsed electric field is proportional to the rate of change of the magnetic field inside the magnetic material of the annular or cylindrical structure.

[0094] 12) The device according to 1), wherein the annular or cylindrical structure 1 is circular in shape.

[0095] 13) The device according to 1), wherein the annular or cylindrical structure 1 is non-circular in shape.

[0096] 14) The device according to 1), wherein the annular or cylindrical structure 1 is a closed structure.

[0097] 15) The device according to 1), wherein the annular or cylindrical structure 1 is a non-closed structure.

[0098] 16) The device according to 1), wherein at least two annular or cylindrical structures 1 are coaxially arranged.

[0099] 17) The device according to 16), wherein the at least two annular or cylindrical structures 1 are separated by a distance equal to the radius of the annular or cylindrical structure.

[0100] 18) The device according to 1), wherein the human or animal subject is placed along the central axis of the device.

[0101] 19) The device according to 1), wherein the electric field pulse of a given amplitude is generated by a voltage applied across the conductive winding 2 of the annular or cylindrical structure 1.

[0102] 20) An apparatus according to 1), wherein the amplitude of the pulsed electric field is controlled in an "open loop" arrangement in which the expected electric field output is known based on the input voltage, the generated current and the system resistance.

[0103] 21) The device according to 1) further includes an additional coil winding for sensing the pulsed electric field generated within the device.

[0104] 22) The device according to 21), wherein the additional coil winding comprises a wire loop 5 which surrounds the cross-section of the annular or cylindrical structure by at least one turn to provide a higher sensitivity to the pulsed electric field.

[0105] 23) The device according to 22), wherein the wire loop 5 induces a voltage, the voltage being equal in magnitude to the rate of change of the magnetic flux passing through the cross section of the annular or cylindrical structure.

[0106] 24) The device according to 22), wherein the wire loop 5 is closed at a high impedance terminal for measuring the voltage around the wire loop.

[0107] 25) A system for therapeutic treatment involving electric fields, comprising:

[0108] annular or cylindrical device 6 for generating a pulsed electric field,

[0109] Drive and sensing circuit system 8,

[0110] a plurality of cables 7 connecting the device 6 to the drive and sensing circuitry 8, and

[0111] A microprocessor 9 which provides a user interface for operating the device 6 and the drive and sensing circuitry 8 .

[0112] 26) A system according to 25), wherein the annular or cylindrical device 6 includes one or more annular or cylindrical structures 1, a conductive winding 2 wound around the annular or cylindrical structure, and an electric wire 3 supplying current to the conductive winding 2.

[0113] 27) The system of 25) wherein the pulsed electric field is used to treat cancer when combined with a pharmacological agent.

[0114] 28) The system of 25), wherein the pulsed electric field is used for targeted osmotic lysis for cancer treatment when combined with a pharmacological agent.

[0115] 29) A system according to 28), wherein the amplitude of the electric field falls within the range of 0.1 V / m to 100 V / m in free space.

[0116] 30) A system according to 28), wherein the pulse of the electric field consists of a forward polarization of approximately 1-50 milliseconds followed by a reverse polarization of similar duration and amplitude.

[0117] 31) A system according to 28), wherein the pulses of the electric field are separated from the end to the start by 5-50 milliseconds.

[0118] 32) A method for therapeutic treatment involving electric fields, comprising generating a pulsed electric field by an annular or cylindrical device 6, wherein the annular or cylindrical device 6 includes one or more annular or cylindrical structures 1, a conductive winding 2 wound around the annular or cylindrical structure, and an electric wire 3 supplying current to the conductive winding 2.

[0119] 33) The method according to 32) also includes using pharmacological agents for targeted osmotic lysis.

[0120] List of reference symbols

[0121] 1 Ring / cylindrical structure

[0122] 2 Conductive winding

[0123] 3 Wires

[0124] 4 Central area of ​​the ring structure

[0125] 5 Wire loop around the cross section of the ring structure

[0126] 6 Ring / cylindrical device

[0127] 7 Cables

[0128] 8 Driving and sensing circuit system

[0129] 9 Microprocessor.

Claims

1. A device for generating a pulsed electric field, comprising: a plurality of annular or cylindrical structures (1) arranged coaxially at intervals that optimize the uniformity of the generated pulsed electric field, a plurality of conductive windings (2) wound around each annular or cylindrical structure, and A plurality of electric wires (3) supply electric current to the conductive winding (2).

2. The device according to claim 1, wherein: The annular or cylindrical structure (1) is made of a magnetic material with high relative magnetic permeability.

3. The device according to claim 2, wherein: The relative magnetic permeability of the magnetic material is 1,000 or higher.

4. The device according to claim 2, wherein: The magnetic material is selected from the group consisting of nanocrystalline alloys of iron, boron and silicon, silicon steel, iron powder, nickel-iron alloy, and ferrite ceramics.

5. The device according to claim 1, wherein: The conductive winding (2) is made of a material selected from the group consisting of aluminum, silver, tin, galvanized steel, phosphor bronze, lead or gold.

6. The device according to claim 1, wherein: The conductive winding (2) is made of copper wire in the range of 10-28 AWG.

7. The device according to claim 1, wherein: The conductive winding (2) is wound on the annular or cylindrical structure into a coil arrangement with 1 to 200 turns.

8. The device according to claim 2, wherein: When the current passing through the conductive winding (2) is inclined, a magnetic field is generated within the magnetic material.

9. The device according to claim 8, wherein: The magnetic field increases or decreases as the current in the conductive winding (2) increases or decreases to generate the pulsed electric field.

10. The device according to claim 9, wherein: The pulsed electric field is generated in the inner region of the annular or cylindrical structure (1) by varying the magnitude of the magnetic field over time.

11. The device according to claim 10, wherein: The magnitude of the pulsed electric field generated is proportional to the rate of change of the magnetic field inside the magnetic material of the annular or cylindrical structure.

12. The device according to claim 1, wherein: The annular or cylindrical structure (1) is circular in shape.

13. The device according to claim 1, wherein: The annular or cylindrical structure (1) is non-circular in shape.

14. The device according to claim 1, wherein: The annular or cylindrical structure (1) is a closed structure.

15. The device according to claim 1, wherein: The annular or cylindrical structure (1) is a non-closed structure.

16. The device according to claim 1, wherein At least two annular or cylindrical structures (1) are coaxially arranged.

17. The device according to claim 16, wherein: The at least two annular or cylindrical structures (1) are spaced apart by a distance equal to the radius of the annular or cylindrical structures.

18. The device according to claim 1, wherein: A human or animal subject is positioned along the central axis of the device.

19. The device according to claim 1, wherein: An electric field pulse of a given amplitude is generated by a voltage applied across the conductive winding (2) of the annular or cylindrical structure (1).

20. The device according to claim 1, wherein The amplitude of the pulsed electric field is controlled in an "open loop" arrangement without the use of a feedback loop, in which the expected electric field output is known based on the input voltage, the generated current and the system resistance.

21. The device of claim 1 further comprising additional coil windings for sensing the pulsed electric field generated within the device.

22. The device according to claim 21, wherein The additional coil winding comprises an electric wire loop (5) which surrounds the cross section of the annular or cylindrical structure by at least one turn to provide a higher sensitivity to the pulsed electric field.

23. The device according to claim 22, wherein: The wire loop (5) induces a voltage, the voltage being equal in magnitude to the rate of change of the magnetic flux passing through the cross section of the annular or cylindrical structure.

24. The device according to claim 22, wherein: The wire loop (5) is closed at the high impedance terminal for measuring the voltage around the wire loop.

25. A system for therapeutic treatment involving electric fields, comprising: An annular or cylindrical device (6) for generating a pulsed electric field, which has a plurality of annular or cylindrical structures (1) coaxially arranged at intervals that optimize the uniformity of the generated pulsed electric field, Drive and sensing circuit system (8), a plurality of cables (7) connecting the annular or cylindrical device (6) to the drive and sensing circuitry (8), and A microprocessor (9) provides a user interface for operating the annular or cylindrical device (6) and the drive and sensing circuitry (8).

26. The system of claim 25, wherein: The annular or cylindrical device (6) comprises one or more annular or cylindrical structures (1), a conductive winding (2) wound around the annular or cylindrical structure, and an electric wire (3) supplying electric current to the conductive winding (2).

27. The system of claim 25, wherein: When combined with pharmacological agents, the pulsed electric fields are used to treat cancer.

28. The system of claim 25, wherein: When combined with pharmacological agents, the pulsed electric fields are used in targeted osmotic lysis for cancer treatment.

29. The system of claim 28, wherein: The magnitude of the electric field falls within the range of 0.1 V / m to 100 V / m in free space.

30. The system of claim 28, wherein: The electric field pulses consist of a 1-50 millisecond forward polarization followed by a reverse polarization of similar duration and amplitude.

31. The system of claim 28, wherein: The electric field pulses are separated from the end to the start by 5-50 milliseconds.

32. A method for therapeutic treatment involving electric fields, comprising generating a pulsed electric field by means of an annular or cylindrical device (6), wherein: The annular or cylindrical device (6) comprises a plurality of annular or cylindrical structures (1), a conductive winding (2) wound around the plurality of annular or cylindrical structures, and an electric wire (3) supplying current to the conductive winding (2), wherein the plurality of annular or cylindrical structures are coaxially arranged at intervals that optimize the uniformity of the generated pulsed electric field.

33. The method of claim 32, further comprising targeted osmotic lysis using a pharmacological agent.

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