Control of irradiation and brain temperature in optogenetic activation

Abstract

A device (22) to be implanted in an organ, the device comprising: (a) an energy consuming device (ECD) (44) configured to (a) receive power and supply energy to the organ; and (b) a resonant circuit (21) configured to (i) receive a magnetic field (MF) and (ii) convert the MF into power, wherein the resonant frequency (25) of the resonant circuit (21) depends on the temperature of the organ, and the resonant circuit (21) is configured to change the intensity of the power supplied to the ECD (44) in response to changes in the temperature of the organ.

Description

Technical Field

[0001] Cross - reference to Related Applications This application claims the benefit of U.S. Provisional Application No. 63 / 507,997, filed on June 14, 2023, the disclosure of which is incorporated herein by reference.

[0002] The present invention generally relates to medical devices based on optogenetics, and more particularly to methods and systems for optogenetic irradiation with thermal protection and closed - loop control.

Background Art

[0003] For example, but not limited to, some neurological diseases such as Parkinson's disease, epilepsy, neuropathic pain, and other types of nervous system diseases and / or disorders can be treated using several techniques.

[0004] For example, U.S. Patent Application Publication No. 2005 / 0143330 by Mandel et al. describes a method for treating Parkinson's disease in patients showing increased resistance to L - dopa administration due to loss of aromatic L - amino acid decarboxylase activity in striatal neurons, including transfection into the caudate nucleus region and / or putamen region with a viral vector encoding AADC. This vector preferably has a promoter system provided for the expression of AADC nucleic acid and is injected at a slow rate at a level designed to restore its activity in tissues undergoing progressive loss of AADC activity. The renewed AADC activity allows the conversion of L - dopa to dopamine in the brain.

[0005] There are implantable devices such as deep brain stimulators (DBS) and responsive neurostimulators (RNS) that apply electrical stimulation to the brain to treat some types of nervous system diseases and / or disorders that are not controlled by drug therapy.

[0006] U.S. Patent No. 11,779,658 by Schorge et al. describes an expression vector containing an artificially engineered gene. The present invention provides an expression vector, nucleic acid, vector particles, therapeutic methods related to these vector particles, and a method for confirming the presence of artificially engineered KCNA1 mRNA in cells, all containing an artificially engineered KCNA1 gene encoding an edited Kv1.1 potassium channel. The merging of features in the artificially engineered KCNA1 gene advantageously enhances the translation and activity of the Kv1.1 protein, improves the detection of KCNA1 gene expression in cells, and allows the features of the artificially engineered KCNA1 gene to be used, for example, in the treatment of epilepsy and similar neurological disorders.

[0007] As will be explained in more detail below, optogenetic activation can be used to treat various neurological diseases (e.g., Parkinson's disease) by irradiating specific regions in the tissue in question (e.g., the human brain). U.S. Patent No. 11,180,537 by Mohanty et al. describes optogenetic modulation with multi-characteristic opsins for vision restoration and other applications.

[0008] Brain catheterization techniques have evolved for the treatment of acute neurological disorders and the prevention of events such as stroke, aneurysms, and stenosis. Stents for cerebral vascular use are required to be designed to be significantly smaller in size (and with strict control of other attributes) compared to stents intended for use in other procedures performed in the general human vascular system. Such requirements and techniques are described, for example, in "A patient guide to brain stent placement" by Jill Novitzke (Journal of vascular intervention in neurology (J Vasc Interv Neurol.) 2009 Apr; 2(2):177-179). The International Organization for Standardization (ISO) specifies test methods for evaluating the electromagnetic compatibility (EMC) of active implantable devices in ISO 14117. Furthermore, the temperature rise in the brain during medical procedures should not exceed approximately 2°C, as stated by regulatory authorities (e.g., ISO, the U.S. Food and Drug Administration (FDA)). As mentioned above, in such procedures, it is important to strictly control the irradiation and temperature. [Overview of the project]

[0009] One embodiment of the present invention described herein provides a device for implantation in an organ, comprising: (a) an energy consuming device (ECD) configured to receive power and to supply energy to the organ; and (b) a resonant circuit configured to (i) receive a magnetic field (MF) and to convert the MF into power, wherein the resonant frequency of the resonant circuit depends on the temperature of the organ, and the resonant circuit is configured to change the intensity of the power supplied to the ECD in response to changes in the temperature of the organ.

[0010] In some embodiments, the device comprises an external MF source configured to generate MF, the MF source comprising (a) an external inductor configured to generate MF in response to receiving a current, and (b) (i) supplying current to the external inductor and sensing changes in the supplied current in response to changes in the intensity of the power supplied to the ECD. In other embodiments, the MF source is configured to supply a current having a given frequency, the resonant circuit is configured to have a first resonant frequency at a first temperature of the organ and to supply a first power to the ECD, the resonant circuit is configured to have a second resonant frequency different from the first resonant frequency at a second temperature of the organ and to supply a second power different from the first power to the ECD. In yet another embodiment, the resonant circuit comprises a capacitor and an inductor connected in series with respect to each other, the capacitance of the capacitor and (b) the inductance of the inductor being configured to change in response to a changing temperature of the organ.

[0011] In some embodiments, the capacitor is configured to change its capacitance by changing the distance between the conductors of the capacitor in response to the temperature at which the organ is altered. In other embodiments, the capacitor includes a microelectromechanical (MEMS) device. In yet another embodiment, the inductor has a ferrite component configured to enhance the induction of the inductor, the permeability of the ferrite component is temperature-dependent, and based on the ferrite component, the inductor is configured to change its inductance in response to the temperature at which the organ is altered.

[0012] In some embodiments, the device includes a subcutaneous MF source embedded between the scalp and an organ and configured to generate MF, the MF source including (i) a further inductor configured to generate MF in response to receiving an electric current, and (ii) a power storage device configured to supply an electric current to an external inductor. In other embodiments, the ECD includes one or more light-emitting diodes (LEDs), one or more of which are covered with a biocompatible material configured to electrically insulate one or more of which LEDs from the tissue surrounding them, and one or more of which are configured to emit light to the brain in response to receiving power. In yet another embodiment, at least one of the LEDs is configured to produce a temperature signal indicating the temperature of an organ.

[0013] In some embodiments, the device includes a processor configured to generate control signals indicating the temperature of an organ in response to a sensed change in the supplied current. In other embodiments, the processor is configured to control the temperature of an organ in a closed loop based on one or more signals indicating the temperature of the organ. In yet another embodiment, the organ includes the head of a patient, and the device is configured to be implanted in the head (i) between the scalp and the skull, or (ii) between the skull and the dura mater, in order to perform optogenetic activation in the brain of the patient.

[0014] In some embodiments, the resonant circuit includes (a) a stent shaped to be implemented in a blood vessel and configured to (i) receive MF and (ii) convert MF into electrical power, and (b) electrical leads connecting the stent to at least an ECD. In other embodiments, the stent includes a nickel-titanium alloy at least partially coated with a biocompatible material configured to electrically insulate the stent from the surrounding tissue. In yet another embodiment, the stent includes (i) a conductive wire and (ii) a layer of polyether ether ketone (PEEK) covering the conductive wire and configured to electrically insulate the conductive wire from the surrounding tissue.

[0015] A method for manufacturing a device intended to be implanted in an organ is further provided according to one embodiment of the present invention, the method comprising manufacturing a resonant circuit for (i) receiving a magnetic field (MF) and (ii) converting the MF into electrical power, wherein the resonant frequency of the resonant circuit depends on the temperature of the organ. The resonant circuit is integrated with an energy-consuming device (ECD) configured to receive electrical power and to impart energy to the organ, and the resonant circuit changes the intensity of the power supplied to the ECD in response to changes in the temperature of the organ.

[0016] In some embodiments, manufacturing a resonant circuit includes (i) manufacturing at least a capacitor and an inductor, wherein at least one of (a) the capacitance of the capacitor and (b) the inductance of the inductor changes in response to the temperature of the organ, and (ii) connecting the capacitor and the inductor in parallel with each other. In other embodiments, manufacturing an inductor includes manufacturing a stent having a conductive coil covered with an electrical insulating layer. In yet another embodiment, the conductive coil includes an alloy of nickel and titanium.

[0017] In some embodiments, the electrical insulating layer includes polyether ether ketone (PEEK). In other embodiments, manufacturing a capacitor includes (i) connecting an ECD to conductive leads, (ii) positioning a first edge and a second edge of the conductive leads with a predetermined gap between them, and (iii) placing a dielectric layer in the gap between the first edge and the second edge.

[0018] A method is further provided for a device, which is implanted in an organ and comprises (i) an energy-consuming device (ECD) that provides energy to the organ in response to receiving power, and (ii) a resonant circuit whose resonant frequency depends on the temperature of the organ, wherein the device receives a magnetic field (MF) from an external MF source. The MF is converted into power, and the intensity of the power supplied to the ECD is changed in response to changes in the temperature of the organ.

[0019] In some embodiments, the method includes generating a second signal indicating the temperature of an organ in response to receiving a first signal indicating a change in the supplied current. In other embodiments, implanting the device in an organ includes (i) implanting the device in the head between the skin and skull of the patient's head, or (ii) implanting the device in the head between the skull and dura mater, and performing optogenetic activation in the patient's brain. In yet another embodiment, implanting the device includes implanting (a) a resonant circuit including a stent shaped to be implemented in a blood vessel to receive MF and convert MF into electricity, and (b) electrical leads connecting the stent to at least an ECD.

[0020] Further provided is a device for generating subcutaneous pulses, comprising: (a) an energy consuming device (ECD) configured to receive power and to energize an organ; (b) a power storage device configured to supply power to the ECD; and (c) an antenna configured to (i) receive a magnetic field (MF) and (ii) convert the MF into power, wherein the conversion of the MF into power is for at least one of (1) charging the power storage device and (2) supplying power to the ECD.

[0021] In some embodiments, the energy storage device includes one or more secondary batteries. In other embodiments, the antenna includes a first inductor and an external MF source configured to generate MF, the MF source including (i) a second inductor configured to generate MF in response to receiving current, and (ii) configured to supply current to the second inductor. In yet another embodiment, the MF source is implemented in a wearable garment.

[0022] In some embodiments, the MF source is implemented in the bed linen. In other embodiments, the device includes a processor configured to (i) sense the temperature of an organ and (ii) control the power supplied to the ECD to maintain the temperature within a predetermined range.

[0023] In some embodiments, the processor is configured to generate a signal indicative of the sensed temperature of the organ and display the sensed temperature to the user across a display. In other embodiments, the organ includes a head, and at least the ECD, the power storage unit, and the antenna are embedded between the skull and the scalp of the head.

[0024] The present invention will be more fully understood from the following detailed description of the embodiments of the present invention, taken in conjunction with the drawings.

Brief Description of the Drawings

[0025] [Figure 1] FIG. 1 is a block diagram schematically showing a closed-loop control of optogenetic activation according to an embodiment of the present invention. [Figure 2] FIG. 2 is a block diagram schematically showing an induction-based thermal switch implemented in an implantable device and an external device used for the optogenetic irradiation treatment of FIG. 1 according to an embodiment of the present invention. [Figure 3A] FIG. 3 is a schematic diagram of a stent-based implantable device according to another embodiment of the present invention. [Figure 3B] FIG. 4 is a schematic diagram of a stent-based implantable device according to another embodiment of the present invention. [Figure 4A] FIG. S is a schematic diagram of a plurality of implantable devices used for the optogenetic irradiation treatment of FIG. 1 according to some embodiments of the present invention. [Figure 4B] FIG. 6 is a schematic diagram of a plurality of implantable devices used for the optogenetic irradiation treatment of FIG. 1 according to some embodiments of the present invention. <()()()()()97> [Figure 5A] Figure 1 is a schematic diagram of an implantable subcutaneous pulse generating device used in optogenetic irradiation treatment according to one embodiment of the present invention. [Figure 5B] This is a schematic diagram illustrating the implementation of the device for generating subcutaneous pulses shown in Figure 5A, according to another embodiment of the present invention. [Figure 5C] This is a schematic diagram of a charging device for transferring energy to an embedded device shown in Figures 3A, 3B, 5A, and 5B, according to another embodiment of the present invention. [Figure 6] This flowchart schematically illustrates a method for performing optogenetic irradiation with thermal protection and closed-loop control according to one embodiment of the present invention. [Figure 7] This flowchart schematically illustrates a method for manufacturing an implantable device based on a stent used in optogenetic irradiation treatment, as shown in Figure 1, according to one embodiment of the present invention. [Modes for carrying out the invention]

[0026] overview Some neurological disorders, such as epileptic seizures, Parkinson's disease, neuropathic pain, and other syndromes, are characterized by abnormal activity of neurons (nerve cells). Neuronal activity is generated by electrochemical changes on the surface of the neuron, resulting in an electric current known as an action potential. Voltage-gated ion channels located in the membrane of nerve cells mediate the passage of ions through the membrane, causing a shift in electrical potential. This shift in potential propagates along the neuron's axon and reaches the presynaptic terminal of the neuron. At the synapse (the small gap between neurons), the opening of calcium channels triggers the release of neurotransmitters (chemicals that mediate activity in the receiving neuron), which then bind to receptors on adjacent neurons, either exciting or inhibiting their activity.

[0027] Treatment for some neurological syndromes generally relies on drug therapies that affect the entire brain (including other organs as part of its systemic effects) nonspecifically. In some cases (e.g., 30% of epilepsy), drug therapy fails to produce the desired effect or causes side effects that can significantly impair the patient's quality of life. Other treatment techniques include electrical stimulation, which uses implanted electrodes to deliver electrical stimulation to specific areas of the brain. While this technique improves upon the accuracy and efficacy of the aforementioned drug therapies, it still lacks precise spatial control because it cannot distinguish between different types of cells within the area receiving the electrical stimulation pulse. More specifically, this technique fails to distinguish between different types of cells because it primarily stimulates white matter axons near the actual target, and it induces excitatory and inhibitory neurons without distinction.

[0028] Other techniques referred to herein as optogenetics enable precise spatial and temporal regulation of selected neurons by inserting genes that express opsins (photosensitive proteins) into selected cell membranes. These opsins are activated by light and regulate neuronal activity through endogenous cellular mechanisms. When exposed to light of a specific wavelength, these opsins change their structure, opening membrane ion channels to allow specific ions to pass into the cell, and, in the case of G protein-coupled receptor (GPCR) opsins, activating an intracellular cascade of endogenous GPCRs.

[0029] Improved spatiotemporal precision capabilities or optogenetics (compared to electrode-based electrical stimulation and chemicals) allow for the precise development of treatments for neurological disorders while reducing the side effect profile. The light transmission profile of red light enables the possibility of developing these treatments minimally invasively and in large brains such as the human brain.

[0030] One embodiment of the present invention described below provides a combination of opsins expressed in relevant brain regions, including the cerebral cortex or deep structures (e.g., the thalamus, hippocampus, basal ganglia, etc.), and a phototherapy device for therapeutic purposes. In some embodiments, the phototherapy device is implanted superficially, for example, between the patient's skull and dura mater, in a minimally invasive procedure. In other embodiments, the phototherapy device is implanted more deeply using any suitable technique, such as techniques used to implant deep brain stimulating electrodes or intravascular intervention techniques.

[0031] In some embodiments, the implantable device is configured to emit light of one or more appropriate wavelengths (e.g., wavelengths between approximately 430 nm and 750 nm) to activate opsins at a location closer to or further away from the optrode (a device designed to emit light and collect fluorescence using a monolithic fiber electrode, for example) depending on the application requirements and the associated neurological adaptation treatment protocol. Furthermore, implanting the device outside the dura mater (e.g., using minimally invasive techniques) reduces the risk of complications associated with intracranial surgery, such as intracranial hemorrhage and infection, as well as the risk of migration and / or fracture of one or more electrodes.

[0032] To prevent tissue damage, a strict temperature range is required for the activation of implantable devices. More specifically, the temperature rise caused by implantable devices must not exceed approximately 2°C, as stated by regulatory authorities [ISO 14117]. Some irradiation techniques, such as photobiomodulation therapy, are related to the light beam. In some embodiments of the present invention, the above 2 o To maximize optical output while maintaining a temperature rise within the C limit, the implantable device is equipped with a continuous digital temperature measurement function. Embodiments of the present invention disclose various techniques for temperature control in the above-described treatment, which are shown in detail in at least Figures 2 to 6 below.

[0033] In some embodiments, the technology of this disclosure allows for minimizing the irradiation intensity necessary to activate GPCR bistable opsins, such as eOPN3, which is cited, for example, in U.S. Patent Application Publication 2021 / 0403518 by Yizhar et al., whose disclosure is incorporated by reference. Thus, the technology of this disclosure allows for reduced power consumption and prevention of tissue overheating. In one embodiment, the implantable device is configured to apply thermal shielding technology instead of thermal measurement. Such thermal shielding technology provides medical staff and patients with a simpler, smaller, and more reliable device compared to code-based digital measurement. Exemplary implementations of such technology are shown in detail in Figures 2, 3A, and 3B below. Such technology may also be implemented to treat several areas in the brain located at different distances from the skull (e.g., in superficial or deep brain tissue). In some embodiments, the implantable device comprises an array of light-emitting diodes (LEDs), each configured to illuminate a specific region in the brain with a predetermined wavelength suitable for (i) the required depth of the area to be treated and (ii) a predetermined wavelength for achieving effective treatment, for example, through inhibition via an endogenous GPCR pathway. In some embodiments, the device's processor is configured to direct different signals to different LEDs in order to treat different regions at different depths of the brain during optogenetic activation. Implementations of these techniques are described in detail in Figures 4A and 4B below.

[0034] In some embodiments, the implantable device may include a pulse generator comprising (i) a control unit (e.g., a processor having temperature measurement capability), (ii) one or more LEDs, an antenna configured to receive a magnetic field (MF) from an external charging device and convert the MF into power intended to be supplied to the LEDs, and (iv) one or more energy storage devices, such as suitable secondary batteries, configured to receive power from the antenna and supply power to one or more LEDs. The external charging device may also be implemented in clothing worn by the patient (e.g., a hat), bed linen (for charging while the patient sleeps), or other suitable type of device. The external charging device comprises a power source and an antenna for wirelessly transmitting energy to the aforementioned antenna of the implantable device. The external antenna may be implemented using, for example, an inductor configured to receive current from the power source and convert the current into MF to be sent to the internal antenna of the implantable device. The implantable device and the external charging device are described in detail in Figures 5A, 5B, and 5C below.

[0035] The technology of this disclosure may be applied to reduce the time and cost associated with surgical procedures. By controlling the irradiation wavelength (e.g., red light), controllable transmittance in biological tissue can be achieved, and the size of the implantable device can be reduced. For example, to obtain maximum efficacy and a reduced invasiveness profile, the device may be applied to irradiate sensitive opsins that respond to wavelengths longer than 530 nm.

[0036] System Description Figure 1 is a schematic block diagram showing a system 10 used to perform closed-loop control of optogenetic activation according to one embodiment of the present invention.

[0037] In some embodiments, the optogenetic activation, whose nature is described in the overview section above, is performed using a system 10 that typically includes an implantable device and an external device. Several implementations of the implantable and external devices are described in detail in Figures 2 to 5C below.

[0038] In some embodiments, the system 10 includes an electroencephalogram (EEG) electrode 12 configured to measure electrical activity in the brain 7 of patient 9 using a small (e.g., approximately 10 mm in diameter) metal disc attached to the scalp of patient 9, as shown in insert 8, which presents a cross-sectional view of the tissue surrounding the brain 7 of patient 9. In other embodiments, the device is embedded between the skull and the dura mater and comprises a smaller disc (e.g., a disc less than approximately 5 mm in diameter). The system 10 further includes an amplifier 14 configured to amplify the signal received from the electrode 12, and a processor 11 configured to receive the amplified signal and to control a photostimulation device 16. The photostimulation device 16 is also referred to as device 16 for brevity in this specification. Several implementations of device 16 and processor 11 are described in detail in Figures 2 to 5C below.

[0039] Typically, the processor 11 comprises an application-specific integrated circuit (ASIC) device customized to perform the functions described herein. The configuration may be downloaded to a computer in electronic form, for example, over a network, or alternatively or additionally, provided and / or stored on a non-temporary tangible recording medium, such as magnetic, optical, or electronic memory connected to an inductive programmer.

[0040] Figure 2 is a schematic block diagram showing an induction-based thermal switch implemented in an embedded device 22 and an external device 33 according to one embodiment of the present invention.

[0041] The implantable device 22 and the external device 33 are also referred to as device 22 and device 33, respectively, in this specification for the sake of brevity. Devices 22 and 33 may, for example, replace device 16 and processor 11 in Figure 1 as described above, or may be used in the optogenetic irradiation treatment in Figure 1.

[0042] In some embodiments, the device 33 is located outside the head of the patient 9, and the device 22 may be implanted in the patient 9, for example, (i) between the skin and scalp, or (ii) between the scalp and the skull, or (iii) between the skull and the dura mater, or in deeper tissue such as blood vessels, as described in Figures 3A and 3B. In this example, the device 33 comprises a processor 11, a flow meter configured to measure the current flowing through the device 33 and referred to herein as an amperemeter 18, and an inductor mounted on an induction coil 20. The device 22 comprises an energy consuming device (ECD), which in this example comprises at least one light-emitting diode (LED) 44 that receives power and emits light directed toward the brain 7 of the patient 9. In other embodiments, instead of the LED 44, the device 22 may comprise any other suitable type of ECD configured to deliver energy to the brain 7 or any other organ of the patient 9 (in other medical procedures).

[0043] In some embodiments, the device 22 includes a resonant circuit 21 configured to (i) receive a magnetic field (MF) from a coil 22 and (ii) convert the MF into power used to operate an LED 44. In this example, the resonant circuit 21 includes a capacitor 23 and a dielectric coil 24 connected in parallel to each other using electrical leads 27. The dielectric coil 24 is also referred to herein as an inductor 24. In some embodiments, in response to receiving the MF, the coil 24 is configured to induce a current to generate the power described above. The LED 44 and the resonant circuit 21 are electrically connected to each other using leads 27. Furthermore, at least one of the components of the device 22, and typically all of the components of the device 22, may be mounted on a circuit board (CB) 29. The circuit board (CB) 29 is biocompatible or coated with a suitable biocompatible coating material (e.g., a polycyclic aromatic hydrocarbon of chemical formula C20H12, also referred to herein as perylene).

[0044] As described in the overview section above, in order to prevent damage to the brain 7, the temperature rise caused by the operation of the implanted device 22 (e.g., by irradiation by the LED 44) should not exceed approximately 2°C. Therefore, it is very important to control the temperature within the brain 7 by controlling the irradiation of the LED 44. In some embodiments, the capacitor 23 and inductor 24 are selected such that at least one of (a) the capacitance of the capacitor 23 and (b) the inductance of the inductor 24 changes in response to changes in the temperature within the brain 7. In such embodiments, the resonant frequency of the resonant circuit 21 depends on the temperature of the brain 7.

[0045] In some embodiments, the frequency of the signal (e.g., MF) received from device 33 is adjusted to the patient's normal body temperature (e.g., approximately 37°C). Inductive coupling requires resonance between the inductor 24 and the capacitor 23. To increase the efficiency of such coupling, the Q-factor (a dimensionless parameter describing how much the resonance is under-damped) of the resonant circuit 21 is selected to be high. Thus, the resonant frequency 25 of the resonant circuit 21 is adjusted so that the device 22 obtains maximum energy at the normal temperature of the brain 7, e.g., approximately 37°C. In this example, the capacitance of capacitor 23 changes with temperature due to changes in the dielectric constant of the capacitor 23 material and mechanical changes in the conductor of capacitor 23. The capacitor is manufactured using a microelectromechanical (MEMS) process to increase the temperature coefficient in a controllable manner. In a MEMS-based capacitor 23, any change in the temperature of the brain 7 results in a change in the distance between the conductive layers of capacitor 23, thereby changing the capacitance of capacitor 23.

[0046] Additionally or alternatively, device 22 includes a ferrite element 26 integrated with the inductor 24 and configured to increase the inductance of the inductor 24. Since the permeability of the ferrite element 26 changes with temperature, the inductance of the inductor 24 also changes in response to changes in the temperature of brain 7.

[0047] In some embodiments, the resonant frequency 25 of the resonant circuit 21 is changed in response to changes in the temperature of the brain 7, for example, the resonant frequency 25 is shifted by an increase in temperature. In this configuration, the resonant circuit 21 is configured to function as negative feedback, so that as the temperature of the brain 7 rises, the resonant frequency 25 of the resonant circuit 21 shifts, reducing the intensity of energy received by the device 22. In such embodiments, the device 22 is configured to receive a smaller portion of the MF energy received from the device 33. This reduces the intensity of power supplied from the device 33 to the LED 44 via the resonant circuit 21.

[0048] In some embodiments, the processor 11 is configured to generate a current supplied to a coil 20, which is configured to generate MF (Medium Frequency) dielectric to an inductor 24 of the device 22. As the temperature of the brain 7 rises, a reduction in the amount of energy consumed by the device 22 leads to a reduction in the amount of current consumed, as measured by the ampereometer 18. In such embodiments, the processor 11 is configured to reduce the current supplied to the coil 20 in order to adjust the irradiation level by the LED 44, thereby lowering the temperature of the brain 7 back to approximately 37°C.

[0049] Additionally or alternatively, the diode of LED44 is configured to measure the temperature inside the brain 7, and the measured temperature is communicated to the processor 11 to control the current supplied to the coil 20 to control the temperature inside the brain 7.

[0050] In some embodiments, the processor 11 is configured to control the irradiation level in a closed loop and thereby control the temperature in the brain 7 in a closed loop, based on at least one of (i) the temperature dependence of the resonant frequency 25, (ii) temperature measurement by the diode of the LED 44, and the sensed level of current (e.g., by the ampereometer 18). The processor 11 is also configured to generate a signal indicating a change in the amount of current drawn in in order to prevent overheating in the brain 7 and to generate a warning to the user of the devices 22, 33 (e.g., by displaying it on a display or by using any other warning technique).

[0051] In some embodiments, based on the temperature dependence of the resonant frequency 25, the resonant circuit 21 is configured to serve as an inherent dimmer of the power supplied to the LED 44.

[0052] Figures 3A and 3B are schematic diagrams of implantable stent-based devices 31 and 32 according to embodiments of the present invention. In this specification, each of the implantable stent-based devices 31 and 32 is also referred to as device 31 and 32 for simplicity, and these devices may replace, for example, device 22 in Figure 2 and / or device 16 in Figure 1 above.

[0053] Refer to Figure 3A here. In some embodiments, the device 31 comprises an induction coil 34 (which also serves as an antenna, as described in the overview above) and a ferrite element 36, which have similar functions to the coils 24 and ferrite elements 26 in Figure 2 described above. In this implementation example, the coil 34 includes a stent made of a nickel-titanium alloy, also known as nitinol (for example, with nickel and titanium in nearly isoatomic proportions, i.e., 49-51%). Note that biocompatible nitinol-based stents are widely used in medical procedures and have mature manufacturing processes.

[0054] In some embodiments, nitinol has shape memory, which is the ability of nitinol to return to its deformed shape by acquiring elasticity even after being deformed at a given temperature.

[0055] In this embodiment, the stent is configured to be implanted in a blood vessel (e.g., in the head) of the patient 9. More specifically, the coil 34 is configured to contract to be implanted using a known minimally invasive procedure and to expand into a pre-designed structure so as not to detach from a selected cavity (e.g., the blood vessel described above) in the head of the patient 9. In this example, the electrical conductivity of the coil 34 is approximately 100 microohms per centimeter. As described in Figure 2 above, the power required to operate the LED 44 is received wirelessly by the inductance, and therefore, a battery or any other energy storage device is not required, thus simplifying the structure of the implantable device 31.

[0056] In some embodiments, the device 31 comprises a capacitor 23 connected in parallel to each other and connected to a coil 34 using lead wires 27, and at least one LED 44. Additionally or alternatively, the capacitor 23 and at least one LED 44 may be mounted on a biocompatible CB 39 (e.g., a CB coated with a biocompatible material such as perylene) and electrically connected using lead wires 27 or traces mounted on the CB 39. The coil 34 is connected to the lead wires 27 using any suitable technique, such as laser welding, but is not limited to these.

[0057] In some embodiments, the coil 34 is covered with a biocompatible and electrically insulating material placed on the outer surface of the coil 34 using a suitable covering (e.g., perylene). The structure of the ferrite element 36 may be similar to that of the ferrite element 26 in Figure 2 described above, or it may have any other suitable size and shape to accommodate the geometric constraints of the stent. In this implementation, the ends of the coil 34 are electrically connected to the ferrite element 36 and CB39 (e.g., using lead wires 27). In some embodiments, the inductive receiving antenna mounted on the coil 34 is designed to be integrated into the stent to reduce the overall size of the coil 34. The coil 34 stent is shaped to match the blood vessel and is embedded in the vessel to prevent dislodgement, but the coil 34 is not required (and / or configured) to provide force to open the blood vessel.

[0058] In some embodiments, in addition to or instead of the ferrite element 36, the blood flowing through the aforementioned blood vessels of the patient 9 may be considered as a ferrite material to enhance the inductance of the antenna mounted on the coil 34, thereby making it possible to reduce the size of the coil 34 and increase its Q-factor.

[0059] Refer to Figure 3B here. Figure 3B shows a device 32, which is another implementation of a stent-based coil 35 having LEDs 44 and capacitors 23 according to one embodiment of the present invention. In some embodiments, the device 32 comprises a CB49 having a plurality of LEDs 44 and capacitors 23, mounted on the CB49 and interconnected using traces 38 of the CB49. In this configuration, the CB49 is electrically connected to the end 41 of the coil 35 using traces 38 (and / or lead wires 27 shown in Figure 3A above).

[0060] In some embodiments, the coil 35 has a shape other than cylindrical symmetry in order to control the spread and direction of the light beam generated by the LED 44.

[0061] In some embodiments, both coils 34 and 35 (in Figures 3A and 3B respectively) have radiopaque markings that can be used by an internist to guide and implant the stent to its intended location within the patient's head. In some embodiments, multiple stent-based devices, such as device 32 (and / or device 31), may be implanted in the patient's head, as described in detail in Figures 4A and 4B below. In one embodiment, each device 32 may operate using different operating frequencies to allow irradiation control. In other embodiments, multiple devices (such as device 32) may operate using the same operating frequency to allow for increased irradiation by the LED 44 and the area irradiated by the LED 44.

[0062] In some embodiments, both implantable devices 31, 32 are configured to receive energy from an external device, such as device 33, which is illustrated and described in detail in Figure 2 above. In the example in Figure 2, device 33 is entirely outside the patient's body. In other embodiments, instead of (or in addition to) device 33, the energy supply device may be implanted within the skull of the patient. In an alternative embodiment, the energy supply device may be implanted between the patient's skull and skin.

[0063] In some embodiments, the energy supply device may include, for example but not limited to, an EEG electrode 12 (shown in Figure 1 above), a MEMS accelerometer such as the ADXL358 product supplied by Analog Devices Inc. (One Analog Way, Wilmington, MA 01887) configured to adjust stimulation in different positions of the patient (e.g., standing, sitting, lying down), and a sensor such as the ADXRS290 product supplied by Analog Devices Inc., configured to adapt to the patient's movements (e.g., tremors, falls, head tilt). These devices are further configured to generate signals that can be used by the processor 11 as inputs for an algorithm to determine (i) whether or not to supply wireless energy to any of the devices 16, 22, 31, and 32 in Figures 1, 2, 3A, and 3B, respectively, and (ii) the amount of energy (e.g., magnetic field strength) that needs to be wirelessly sent to an implantable device that provides the required level of irradiation (by the LED 44) to obtain the desired medical effect when treating the brain 7 of the patient 9.

[0064] In other embodiments, instead of the coated nitinol described above, at least one stent of coils 34 and 35 includes (i) a conductive wire (for example, shown as trace 38 in Figure 3B), and (ii) a layer of polyether ether ketone (PEEK) covering the conductive wire and configured to electrically insulate the conductive wire from the surrounding tissue, such as blood vessels. Since PEEK is biocompatible and has memory shape properties similar to (but not usually identical to) nitinol, the combination of a conductive wire and PEEK coating can be used on at least one of coils 34 and 35. PEEK also has a high electrical resistivity (greater than about 5 × 10¹⁶ ohms per centimeter) to prevent undesirable leakage of current along the stent, and PEEK coatings are typically manufactured using an injection molding process.

[0065] In some embodiments, the fabrication of the PEEK-based stent for coils 34 and / or 35 comprises a first process operation and a second process operation. In the first operation, conductive wires are formed into the shape of an antenna based on the stent and configured to receive energy from an energy supply device 33 and wiring connecting the LED 44 and the capacitor 23. In some embodiments, the connection between the LED 44 and the capacitor 23 is made at the wafer level, reducing the size of each embedded device (e.g., device 31 and / or device 32) and enabling mass production of PEEK-based embedded devices.

[0066] In some embodiments, in the first operation, the capacitor 23 is manufactured by utilizing the mechanical properties of the material used for the conductive wire. In one embodiment shown in Figure 3B, the electrodes of the capacitor 23 are formed from the edges 37 of a conductive wire (e.g., trace 38 in Figure 3B), and the capacitor 23 is formed by inserting (placing) PEEK between the edges 37 of the trace 38. This manufacturing technique reduces the size of the implanted device (e.g., device 32) and simplifies the structure (by reducing the number of components). Furthermore, this manufacturing technique simplifies the manufacturing cost of the implanted device by manufacturing the capacitor 23 together with the coil connecting the LED 44. In some embodiments, the antenna design of the implanted device (e.g., device 32) does not require a ferrite element, and instead uses blood surrounding the coil 35. In some embodiments, this implementation is applied to reduce the size of the stent-based antenna and to increase the Q factor of the coil 35.

[0067] In some embodiments, the second operation involves placing a conductive wire in the mold (e.g., instead of the trace 38) and covering it with injected PEEK to obtain the required mechanical properties of the coil 35 stent. Note that PEEK does not absorb wavelengths of light generated by the LED 44 (e.g., wavelengths higher than approximately 530 nm). Therefore, most of the light emitted by the LED 44 is used for optogenetic activation.

[0068] In some embodiments, the stent of coil 35 may be formed using a thermoforming process on a pre-fabricated mixture of pure PEEK and PEEK swallowing wire to obtain the desired shape. Also, as described above, in some embodiments, the shape of coil 35 must be other than cylindrical symmetry to allow control of the spread and direction of light toward the brain 7. Also, coil 35 may include radiopaque markings that can be used by an internist to guide and implant the stent (implemented on coil 35) in the intended location of the stent within a predetermined blood vessel of the patient 9, as described above.

[0069] In some embodiments, as described in detail in Figures 4A and 4B, multiple stent-based devices, such as device 32, may be implanted in the head of patient 9. In one embodiment, each device 32 may operate using a different operating frequency to enable irradiation control. In another embodiment, multiple devices 32 may operate using the same operating frequency to enable increased irradiation by the LED 44 and increased area irradiated by the LED 44.

[0070] In some embodiments, both implantable devices 32 are configured to receive energy from an external device, such as device 33, which is illustrated and described in detail in Figure 2 above. In the example in Figure 2, device 33 is entirely outside the body of patient 9. In other embodiments, instead of (or in addition to) device 33, the energy supply device may be implanted within the skull of patient 9. In an alternative embodiment, the energy supply device may be implanted between the skull and skin of patient 9.

[0071] In some embodiments, the energy supply device (e.g., device 33) and / or implantable device 32 may include, but are not limited to, EEG electrodes 12 (as shown in Figure 1 above), MEMS accelerometers such as the aforementioned ADXL358 product configured to adjust stimulation in different positions of the patient (e.g., standing, sitting, lying down), and sensors such as a gyroscope such as the aforementioned ADXRS290 product, also supplied by Analog Devices Inc., configured to adapt to the patient's movements (e.g., tremors, falls, head tilts). These devices are configured to produce signals that can be used by the processor 11 as inputs for an algorithm to determine (i) whether or not to supply wireless energy to device 32, and (ii) the amount of energy (e.g., magnetic field strength) that needs to be wirelessly sent to device 32 to provide the necessary level of irradiation (by LED 44) to obtain the required medical effect when treating the brain 7 of patient 9.

[0072] The specific configurations of devices 33, 22, 31, and 32 in Figures 2, 3A, and 3B are shown as examples to illustrate the specific problems addressed by embodiments of the present invention and to demonstrate the application of these embodiments in improving the performance of a system for performing brain therapeutic procedures using closed-loop control as described above (e.g., system 10 in Figure 1 above). However, embodiments of the present invention are by no means limited to this particular type of exemplary device and / or system 10, and the principles described herein may similarly apply to other types of systems that may be used for optogenetic activation.

[0073] Figures 4A and 4B are schematic diagrams of multiple implantable devices 55a and 55b used in the optogenetic irradiation treatment of Figure 1 according to some embodiments of the present invention.

[0074] In some cases, optogenetic activation requires activation and / or inhibition in multiple therapeutic regions within the brain 7. At least two of these therapeutic regions may be located at different depths within the patient's skull 9. Note that longer wavelengths (e.g., 625 nm) penetrate deeper into the tissue compared to shorter wavelengths (e.g., 530 nm).

[0075] In some cases, optogenetic activation requires post-implantation control of which LEDs are activated. Furthermore, the required control may be patient-specific, treatment-specific, or time-specific. Thus, controlling each LED or region using separate control wires can increase resistance paths, reduce device reliability, increase size, and increase the complexity of manufacturing such lighting systems.

[0076] In some embodiments, multiple irradiation devices 55a and 55b are implanted in the head of patient 9 using systems 50 and 56 in Figures 4A and 4B, respectively. At least one of the devices 55a and 55b may be the same as any of the devices 22, 31, and 32 in Figures 2, 3A, and 3B, respectively.

[0077] In some embodiments, each of systems 50, 56 includes a processor 11 for controlling the irradiation of devices 55a, 55b implanted in several locations on the head of the patient 9 to irradiate different regions in the brain 7. For example, to differentially apply light to different regions at different times, the processor 11 is configured to generate control signals for activating devices 55a and 55b.

[0078] Refer to Figure 4A here. In some embodiments, the system 50 includes a bandpass filter 53 implemented using any preferred type of RLC circuit. In this example, the bandpass filter is implemented using a series-connected capacitor 52 and inductor 54, or any other suitable configuration. The characteristics of the capacitor 52 and inductor 54 are selected to obtain the required bandpass filter. In some embodiments, the control signals have different frequencies to simultaneously activate each device 55 or a group of devices 55. In such embodiments, the processor 11 activates different devices 55 at different times.

[0079] The depth of light penetration depends on the wavelength of light. In this example, the maximum response (to light) of the photosensitive protein implemented in brain 7 was obtained at a wavelength of approximately 527 nm, and approximately 50% of the response (sufficient to perform the procedure) was obtained at a wavelength of approximately 630 nm.

[0080] In an exemplary implementation, devices 55a and 55b each comprise different LEDs 44a and 44b configured to emit different wavelengths of light, for example, 527 nm and 620 nm, respectively. In some cases, there may be a trade-off between the efficacy and depth of irradiation. For example, a wavelength of 527 nm has maximum efficacy but penetrates to a shallow depth, while 700 nm can penetrate to any location in the brain 7, but the irradiation has a low effect on the photosensitive protein used in this example. In this implementation, the processor 11 is configured to activate (i) device 55a for performing treatment in a shallow region located close to the skull, and (ii) device 55b for performing treatment in a deeper region within the skull.

[0081] In other exemplary implementations, devices 55a and 55b are equipped with similar LEDs 44a and 44b configured to emit the same wavelength of light, for example, 630 nm, but need to be activated at different times. Furthermore, devices 55a and 55b have different bandpass filters 53. In this implementation, the processor 11 is configured to activate (i) device 55a, which performs a procedure at a first time interval using a first control signal having a first frequency, and (ii) device 55b, which performs a procedure at a second time interval different from the first time interval using a second control signal having a second frequency different from the first frequency. Thus, the differential activation of devices 55a and 55b is performed using the analog technique implemented in the aforementioned bandpass filter 53.

[0082] Refer to Figure 4B here. In some embodiments, devices 55a and 55b are similar to those presented in Figure 4A above, but activation is performed using digital technology. In some embodiments, each of the devices 55a and 55b has a predetermined address, and the processor 11 is configured to send activation signals to each specific device in order to perform procedures at different times, different locations, and different depths within the skull of patient 9, as described in detail in Figure 4A above. In this example, in the example of Figure 4B, the aforementioned sending is implemented in software using a diode 57, a switch 59, and a hold-up capacitor 58.

[0083] In some embodiments, the technology described in Figures 4A and 4B reduces the number of components (e.g., processors, wiring, antennas, etc.) implanted in the patient's head. Additionally, devices 55a and 55b of systems 50 and 56 wirelessly receive energy from external devices such as device 33, whose structure and function are described in detail in Figure 2.

[0084] Figure 5A is a schematic diagram of an implantable subcutaneous pulse generating device, referred to herein as device 60, used in the optogenetic irradiation treatment of Figure 1 according to one embodiment of the present invention. In this example, device 60 is implanted between the skin and skull of the patient's head.

[0085] In some embodiments, the device 60 includes a pulse generator comprising (i) a control unit 62 such as the processor 11 shown in Figures 1 to 4B above, and (ii) one or more light-emitting device devices such as one or more LEDs 44 shown in Figures 1 to 4B above. In some embodiments, the processor 11 includes a temperature sensing circuit configured to generate a signal indicating the temperature in a region of the brain 7 near the processor 11.

[0086] In some embodiments, the device 60 includes an antenna 61 (inductor 24 in Figures 2, 3A, and 3B, and coils 34 and 35 based on a stent) configured to receive a magnetic field from an external charging device (such as the device shown in Figure 5C later, or device 33 shown in Figure 2 above) and to convert the magnetic field into power intended to be supplied to the LED 44.

[0087] In some embodiments, the device 60 further comprises an energy storage device 63, such as a rechargeable battery pack, configured to receive power from the antenna 61 and to supply power to one or more LEDs 44, for example, as described in detail in Figure 2 above. In some embodiments, one or more batteries comprise one or more medical-grade solid-state batteries. Such batteries are configured to hold approximately 50 microampere-hours (uAH) per cell and have dimensions of approximately 10 mm, 4 mm, and 0.6 mm in the XYZ dimensions, respectively. For example, the solid-state batteries may be implemented using Stereax® M50 products, provided by Ilika Technologies Ltd (Southampton SO16 7NS, UK), which have a footprint of 10.75 mm × 3.75 mm and a thickness of approximately 0.6 mm.

[0088] Furthermore, the scalp of an adult human is approximately 500 cm², which can easily accommodate the size of the energy storage device 63. 2 It has a larger surface area. Also, a deep brain stimulator (DBS) typically requires a battery with a capacity of about 200 mAh, sufficient to operate the DBS for about 30 days. In some embodiments, the energy storage device 63 is configured to connect multiple batteries in parallel, thereby having sufficient capacity to supply power to the device 60 for more than two days of operation. The energy storage device 63 is also configured to be wirelessly rechargeable, as described in Figure 2 above.

[0089] Figure 5B is a schematic diagram illustrating the implementation of the subcutaneous pulse generating device 60 of Figure 5A according to another embodiment of the present invention. In this example, the device 60 comprises a biocompatible package 64 configured to include a control unit 62 and a power storage device 63. An antenna 61 extends from the package 64 along the periphery of the skull surface, and both the package 64 and the antenna 61 are embedded in the skull surface of the patient 9.

[0090] Figure 5C is a schematic diagram of a charging device 66 for transferring energy to an embedded device 60 shown in Figures 5A and 5B, according to another embodiment of the present invention.

[0091] In some embodiments, the external charging device 66 may be mounted on clothing, in this example, on a hat 68 worn by the patient 9. In this implementation, the external charging device 66 comprises a power source mounted on a secondary battery 67 and an antenna 69 extending from the battery 67 for wirelessly supplying energy to the antenna 61 of the implantable device 60 (for example, across a magnetic field as described in detail in Figure 2 above, or using any other suitable technique).

[0092] In some embodiments, the antenna 69 of device 66 may be implemented using an inductor configured to (i) receive current from a secondary battery 67 and (ii) convert the current into a magnetic field that is sent to the antenna 61 of the embedded device 60.

[0093] In an alternative embodiment, the device 66 may be implemented in the bed linen for charging the energy storage device 63 while the patient 9 is sleeping, or in any other suitable type of device placed in contact with the patient 9's head.

[0094] The specific configurations of devices 60 and 66 in Figures 5A to 5C are shown as examples to illustrate the specific problems addressed by embodiments of the present invention and to demonstrate the applicability of these embodiments to improving the performance of systems for performing brain therapeutic procedures using closed-loop control, as described in the example of system 10 in Figure 1 above. However, embodiments of the present invention are by no means limited to these particular types of exemplary configurations, and the principles described herein may also be applied to other types of implantable and charging devices that can be used for optogenetic activation and may have any suitable configuration of the above-described components or other components configured to perform the operations described in Figures 1 to 5C above.

[0095] Figure 6 is a schematic flowchart illustrating a method for performing optogenetic irradiation with thermal protection and closed-loop control according to one embodiment of the present invention.

[0096] In some embodiments, the method shown in Figure 6 is implemented using devices 22 and 33 of Figure 2 described above, but this method can also be implemented using any of the devices shown in Figures 1 to 5C by making the necessary modifications.

[0097] The method begins with a device implantation step 100, in which a device 22 having an LED 44 and a resonant circuit 21 having a capacitor 23 and an inductor 24 is implanted in the head of patient 9. The resonant frequency 25 of the resonant circuit 21 depends on the temperature of the brain 7, as described in detail in Figures 1 and 2 above.

[0098] In the power generation step 102, as described in detail in Figure 2 above, MF is received from the coil 20 of device 33, and the MF is converted into power and supplied.

[0099] In the temperature control step that concludes this method, in response to sensing changes in brain temperature (for example, by sensing a decrease in current consumption by the ampereometer 18 of device 33), the processor 11 is configured to change the intensity of the current supplied to the coil 20, as described in detail in Figure 2 above, as a result of reducing the MF supplied to device 22 and therefore the power supplied to the LED 44.

[0100] Figure 7 is a schematic flowchart illustrating a method for manufacturing an implantable device 32 based on a stent used in the optogenetic irradiation treatment shown in Figure 1, according to one embodiment of the present invention.

[0101] The method begins with a stent manufacturing step 200, which involves manufacturing a coil 35 based on a stent, configured to be implanted in a blood vessel, as described in detail in Figure 3B above. In this example, the coil 35 contains nitinol, but in other examples, as described in Figure 3B above, the coil 35 may contain any suitable type of conductive wire.

[0102] In coating step 202, (i) at least a portion of the nitinol-based coil 35 is coated with a biocompatible electrically insulating layer placed on the outer surface of the coil 35 using a suitable zinc plating coating (e.g., perylene), or alternatively, (ii) PEEK is coated over the conductive wires of the coil 35 to electrically insulate the conductive wires from the blood vessels surrounding the conductive wires, as described in detail in Figures 3A and 3B above.

[0103] In LED connection step 204, one or more LEDs 44 are connected to any suitable type of electrical lead wire (e.g., the electrical trace 38 of CB49) and along any suitable type of electrical lead wire, as described in detail in Figure 3B above.

[0104] In the capacitor formation step 206, as described in detail in Figure 3B above, the capacitor 23 of the device 32 is formed by positioning the edges 37 of the conductive lead wires (e.g., electrical traces 38) with predetermined gaps between them and placing a dielectric layer (e.g., made of PEEK) in the gaps.

[0105] In the stent lead wire connection step 208, which concludes this method, the edge 41 of the coil 35 is electrically connected to the electrical lead wire and, in this example, to the electrical trace 38 of CB49, as described in detail in Figure 3B above.

[0106] The embodiments described herein primarily deal with techniques for treating Parkinson's disease, epilepsy, neuropathic pain, and other neurological disorders and / or conditions using optogenetic irradiation with thermal protection and closed-loop control. However, the methods and systems described herein can also be used for other applications, such as electrical stimulation, that are suitable for treating Parkinson's disease, epilepsy, neuropathic pain, and other types of neurological disorders and / or conditions.

[0107] Accordingly, it will be understood that the embodiments described above are illustrative and that the present invention is not limited to what has been specifically shown and described above. Rather, the scope of the present invention includes both combinations and partial combinations of the various features described above, as well as variations and modifications thereof, which may be recalled by those skilled in the art when reading the above description and which have not been disclosed in the prior art. Documents incorporated by reference in this application should be considered an integral part of this application, except that, to the extent that any term is defined in those incorporated documents in a manner that contradicts the definitions made expressly or implicitly herein, only the definitions herein should be considered.

Claims

1. A device that is implanted inside an organ, An energy consuming device (ECD) configured to receive electricity and supply energy to the aforementioned organs, It is a resonant circuit, (i) Receiving a magnetic field (MF), (ii) Converting the MF into the power, A resonant circuit configured to perform the following: Equipped with, The resonant frequency of the aforementioned resonant circuit depends on the temperature of the organ. The resonant circuit is configured to change the intensity of the power supplied to the ECD in response to the change in the temperature of the organ. device.

2. An external MF source for the aforementioned organ, comprising an MF source configured to generate the aforementioned MF, The aforementioned MF source is, (a) comprising an external inductor configured to generate the MF in response to receiving current, (b) (i) supplying the current to the external inductor, (ii) Sensing the change in the current supplied in accordance with the change in the intensity of the power supplied to the ECD, Configured to perform, The device according to claim 1.

3. The MF source is configured to supply the current having a given frequency, The resonant circuit is configured to have a first resonant frequency at a first temperature of the organ and to supply a first power to the ECD, and the resonant circuit is configured to have a second resonant frequency different from the first resonant frequency at a second temperature of the organ and to supply a second power different from the first power to the ECD. The device according to claim 2.

4. The aforementioned resonant circuit comprises a capacitor and an inductor connected in parallel with each other. (a) The capacitance of the capacitor and (b) The inductance of the inductor and At least one of them is configured to change in response to the altered temperature of the organ, The device according to claim 3.

5. Depending on the changed temperature of the organ, the capacitor is configured to change its capacitance by changing the distance between the conductors of the capacitor. The device according to claim 4.

6. The aforementioned capacitor includes a microelectromechanical (MEMS) device. The device according to claim 5.

7. The inductor has a ferrite component configured to enhance the induction of the inductor, The permeability of the ferrite component depends on the temperature. Based on the ferrite component, the inductor is configured to change its inductance in response to the changed temperature of the organ. The device according to claim 4.

8. The system includes a subcutaneous MF source embedded between the scalp and the organs and configured to generate the MF, The aforementioned MF source is, (i) A further inductor configured to generate the MF in response to receiving current, (ii) A power storage device configured to supply the current to the external inductor, Equipped with, The device according to claim 1.

9. The ECD comprises one or more light-emitting diodes (LEDs), and the one or more LEDs are covered with a biocompatible material configured to electrically insulate the one or more LEDs from the tissue surrounding them. The one or more LEDs are configured to emit light to the brain in response to receiving the power. The device according to claim 1.

10. At least one of the LEDs is configured to generate a temperature signal indicating the temperature of the organ. The device according to claim 9.

11. A processor is provided which generates a control signal indicating the temperature of the organ in response to the sensed change in the supplied current, The device according to any one of claims 2 to 10.

12. The processor is configured to control the temperature of the organ in a closed loop based on one or more signals indicating the temperature of the organ. The device according to claim 11.

13. The aforementioned organs include the patient's head, The device is used to perform optogenetic activation in the patient's brain. (i) Between the scalp and the skull, (ii) Between the skull and the dura mater, The head is configured to be embedded in the head, The device according to any one of claims 2 to 10.

14. The aforementioned resonant circuit is (a) Shaped to be implemented inside blood vessels, (i) Receiving the aforementioned MF, (ii) Converting the MF into the power, A stent configured to perform the following actions: (b) an electrical lead wire connecting the stent and at least the ECD, Equipped with, The device according to any one of claims 2 to 10.

15. The stent comprises a nickel-titanium alloy at least partially coated with a biocompatible material configured to electrically insulate the stent from the surrounding tissue. The device according to claim 14.

16. The aforementioned stent is (i) A conductive wire and (ii) A layer of polyether ether ketone (PEEK) covering the conductive wire and configured to electrically insulate the conductive wire from the tissue surrounding the conductive wire, including, The device according to claim 14.

17. A method for manufacturing a device intended to be implanted in an organ, wherein the method is: (i) Receiving a magnetic field (MF), (ii) Converting the MF into electricity, To manufacture a resonant circuit for which the resonant frequency of the resonant circuit depends on the temperature of the organ, The resonant circuit is integrated with an energy consuming device (ECD), wherein the ECD is configured to receive the power and supply energy to the organ, and the resonant circuit changes the intensity of the power supplied to the ECD in accordance with the temperature change of the organ, and the resonant circuit is integrated with the ECD. Methods that include...

18. Manufacturing the aforementioned resonant circuit is (i) Manufacturing at least a capacitor and an inductor, (a) The capacitance of the capacitor and (b) The inductance of the inductor and At least one of these involves manufacturing at least a capacitor and an inductor that change in response to the temperature of the organ, (ii) Connecting the capacitor and the inductor in parallel with each other, including, The method according to claim 17.

19. Manufacturing the inductor includes manufacturing a stent having a conductive coil covered with an electrical insulating layer. The method according to claim 18.

20. The conductive coil includes an alloy of nickel and titanium. The method according to claim 19.

21. The aforementioned electrical insulating layer contains polyether ether ketone (PEEK). The method according to claim 19.

22. Manufacturing the aforementioned capacitor involves, (i) Connecting the ECD to a conductive lead wire, (ii) Positioning the first edge and the second edge of the conductive lead wire with a predetermined gap between them, (iii) Placing a dielectric layer in the gap between the first edge and the second edge, including, The method according to claim 18.

23. Implanted inside the organs, (i) an energy consuming device (ECD) that receives electricity and supplies energy to the organ in accordance with the electricity, (ii) A resonant circuit wherein the resonant frequency of the resonant circuit depends on the temperature of the organ, In a device having, the magnetic field (MF) is received from an MF source outside the organ, Converting the aforementioned MF into the aforementioned power, The intensity of the power supplied to the ECD is changed in accordance with the temperature change of the organ, A method that includes this.

24. The MF source includes an external inductor that generates the MF in response to the current it receives. Receiving the MF includes sensing the change in the supplied power in accordance with the change in the intensity of the power supplied to the ECD. The method according to claim 23.

25. The system includes generating a second signal indicating the temperature of the organ in response to receiving a first signal indicating a change in the supplied current, The method according to claim 24.

26. Implanting the device in the aforementioned organ is, (i) Between the skin of the patient's head and the skull, (ii) Between the skull and the dura mater of the head, The device is embedded in the head, To perform optogenetic activation in the brain of the aforementioned patient, including, The method according to any one of claims 23 to 25.

27. Embedding the aforementioned device means (a) The resonant circuit includes a stent shaped to be implemented inside a blood vessel to receive the MF and convert the MF into the power, (b) an electrical lead wire connecting the stent and at least the ECD, Including embedding The method according to any one of claims 23 to 25.

28. An energy consuming device (ECD) configured to receive electricity and supply energy to organs, A power storage device configured to supply the power to the ECD, (i) Receiving a magnetic field (MF), (ii) Converting the MF into the power, (a) Charging the energy storage device, (b) supplying the power to the ECD, For at least one of the following: converting the MF into the power, An antenna configured to perform the following: A device that generates subcutaneous pulses, equipped with the necessary components.

29. The aforementioned energy storage device comprises one or more secondary batteries. The device according to claim 28.

30. The antenna comprises a first inductor and an external MF source configured to generate the MF, The aforementioned MF source is, (i) comprising a second inductor configured to generate the MF in response to receiving current, (ii) A second inductor configured to supply the current, The device according to claim 28.

31. The aforementioned MF source is implemented in wearable clothing. The device according to claim 30.

32. The aforementioned MF source is implemented in the bed linen. The device according to claim 30.

33. (i) Sensing the temperature of the organs, (ii) Controlling the power supplied to the ECD in order to maintain the temperature within a predetermined range, A processor configured to perform the following: The device according to claim 28.

34. The processor is configured to generate a signal indicating the sensed temperature of the organ and to display the sensed temperature to the user on a display. The device according to claim 28.

35. The aforementioned organs include the head, At least the ECD, the energy storage unit, and the antenna are embedded between the skull and scalp of the head. The device according to any one of claims 28 to 34.

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