Dynamic electroporation

Abstract

Techniques for dynamic electroporation of cells of a recipient of an implantable medical device are presented herein. A carrier member having one or more electroporation electrodes is positioned in a spatial region proximate to cells of the recipient. The one or more electroporation electrodes are electrically connected to an external electroporation device, and a therapeutic material to be transferred into the cells of the recipient is delivered proximate to the cells. The carrier member is moved through the spatial region while a series of electroporation signals generated by the external electroporation device are applied to the electroporation electrodes to generate an electroporation electric field proximate to the cells. Due to the movement of the carrier member (and thus the electroporation electrodes), the location of the trajectory of the electroporation electric field varies within the spatial region over time.

Description

[0001] background Technical Field

[0003] This invention generally relates to dynamic electroporation of cells within recipients of implantable medical devices. Background Technology

[0005] Over the past few decades, medical devices have provided a wide range of therapeutic benefits to recipients. Medical devices can include internal or implantable components / devices, external or wearable components / devices, or combinations thereof (e.g., devices having an external component that communicates with the implantable component). Medical devices, such as conventional hearing aids, partially or fully implantable hearing prostheses (e.g., bone conduction devices, mechanical stimulators, cochlear implants, etc.), pacemakers, defibrillators, functional electrical stimulation devices, and other medical devices, have been successful for many years in performing life-saving and / or lifestyle improvement functions and / or recipient monitoring.

[0006] Over the years, the types of medical devices and the range of functions they perform have increased. For example, many medical devices, sometimes referred to as “implantable medical devices,” now typically include one or more instruments, devices, sensors, processors, controllers, or other functional mechanical or electrical components that are permanently or temporarily implanted into a recipient’s body. These functional devices are typically used to diagnose, prevent, monitor, treat, or manage diseases / injuries or their symptoms, or to study, replace, or modify anatomical structures or physiological processes. Many of these functional devices utilize power and / or data received from an external device that is part of or operates in conjunction with the implantable component. Summary of the Invention

[0007] In one aspect, a method is provided. The method includes: inserting a carrier member comprising a plurality of electroporation electrodes into a spatial region within the body of a recipient; introducing therapeutic material into the spatial region; and dynamically electroporating a cell population located adjacent to the spatial region to transfer the therapeutic material into the cell population.

[0008] In another aspect, a method is provided. The method includes: positioning one or more electroporation electrodes in a spatial region adjacent to cells in a recipient's body, wherein the one or more electroporation electrodes are electrically connected to an external electroporation device; delivering therapeutic material configured for transfer to the recipient's cells into the spatial region; and while simultaneously moving the one or more electroporation electrodes through the spatial region along a path, applying a series of current pulses from the external electroporation device to the one or more electroporation electrodes to generate at least one dynamic electroporation electric field near the cells.

[0009] In another aspect, a method is provided. The method includes: inserting a carrier member comprising a plurality of electroporation electrodes into a spatial region within the body of a recipient; introducing therapeutic material into the spatial region; moving the carrier member through the spatial region; and, while the carrier member moves through the spatial region, delivering a series of electroporation signals to the electroporation electrodes to generate a dynamic electroporation electric field, wherein the position of the trajectory of the dynamic electroporation electric field varies over time within the spatial region. Attached Figure Description

[0010] Embodiments of the present invention are described herein in conjunction with the accompanying drawings, wherein:

[0011] Figure 1A This is a schematic diagram illustrating a cochlear implant system including an electroporation subsystem according to certain embodiments presented herein;

[0012] Figure 1B This is another schematic diagram illustrating certain embodiments according to the present document. Figure 1A Cochlear implant system;

[0013] Figure 2A This is another schematic diagram illustrating a standalone electroporation subsystem according to certain embodiments presented herein;

[0014] Figure 2B These are schematic diagrams illustrating certain embodiments according to the present document. Figure 2A An independent electroporation subsystem is used for dynamic electroporation applications;

[0015] Figure 2C These are schematic diagrams illustrating certain embodiments according to the present document. Figure 2A An independent electroporation subsystem is used for another application of dynamic electroporation;

[0016] Figure 3A , 3B 3C is a series of schematic diagrams illustrating dynamic electroporation according to certain embodiments presented herein; and

[0017] Figure 4 This is a flowchart of a method according to certain embodiments presented herein;

[0018] Figure 5 This is a flowchart of another method according to some embodiments presented herein;

[0019] Figure 6 This is a schematic diagram illustrating another cochlear implant system according to certain embodiments presented herein;

[0020] Figure 7AThis is a schematic diagram illustrating a portion of a stimulation component in a first arrangement according to certain embodiments presented herein; and

[0021] Figure 7B This is a schematic diagram illustrating a second arrangement according to certain embodiments presented herein. Figure 7A The stimulation component.

[0022] Figure 7C This is a schematic diagram illustrating a portion of a stimulation component according to certain embodiments presented herein. Detailed Implementation

[0023] Electroporation refers to applying an electric field to a cell in a manner that generates an electric potential (i.e., a voltage difference) across the cell membrane, which in turn temporarily opens pores in the cell's lipid bilayer membrane. These electrically opened pores can be used, for example, to allow therapeutic materials to pass through the cell membrane into the cell (i.e., when a potential difference is applied to the cell, the electrically opened pores in the cell membrane allow material to flow into the cell). After the potential is removed, the pores in the cell membrane close, leaving the therapeutic material retained within the cell. Thus, by enhancing and achieving… wait Medical implants alter the biological composition of cells through manipulation, and electroporation can be used in medical implants.

[0024] For successful electroporation, cells are typically exposed to an electric field for a sufficient duration to allow the desired therapeutic material to migrate across the cell membrane. This electric field, sometimes referred to herein as the “electroporation field,” has a localized field strength ranging from approximately 50 microvolts per micrometer (µV / µm) to approximately 500 µV / µm. (Generally, the voltage required to generate a field with sufficient strength for electroporation depends largely on the geometry, relative position, and distance of the anode and cathode electrodes, and also on the medium between the electrodes and the cell.)

[0025] There are several types of implantable medical devices that operate by delivering electrical (current) stimulation to the recipient's nerves, muscles, tissue fibers, or other cells. These implantable medical devices typically deliver electrical stimulation to compensate for the recipient's defects. For example, certain implantable medical devices, such as cochlear implants, are often proposed when a recipient experiences sensorineural hearing loss due to the absence or destruction of the cochlear hair cells that convert acoustic signals into nerve impulses. Auditory brainstem stimulators are another type of implantable medical device prosthesis that can be proposed when a recipient experiences sensorineural hearing loss due to damage to the auditory nerve.

[0026] "Static" electroporation has been performed using cochlear implants (i.e., where the electrodes(s) delivering / generating the electroporation electric field do not move during electroporation). For example, one or more electrodes are positioned in the inner ear (cochlea), and a solution containing therapeutic material to be transferred (e.g., a viral vector including exogenous genetic material) is introduced into the inner ear. Once in place, current is delivered to cells adjacent to at least one of the inserted electrodes to provide an electric shock to those cells adjacent to at least one electrode. That is, a high-voltage electric field is delivered to the cells, which causes pores within the membranes of those cells to open, thereby allowing therapeutic material to enter the cells (e.g., the cell membrane becomes temporarily (cell transfer) or permanently (cell ablation) permeable, allowing substances that normally cannot enter the target cells to cross the cell membrane and enter the interior of the target cells).

[0027] Static electroporation has been used in various in vitro and in vivo Applications include scientific research, cancer treatment, gene therapy, and vaccination. The efficiency of static electroporation is determined by the number of cells successfully electroporated. Typical methods to increase yield include increasing the concentration of material to be transferred to the cells relative to the number of cells, changing the electroporation voltage or field strength, or optimizing the number of electrical pulses. However, for static electroporation, based on the location and size of the electrodes, electroporation is limited to nearby cells, thus the conversion efficiency is suboptimal. Although a larger electric field can be generated to reach more cells, this approach can lead to damage to cells within the electric field. Therefore, static electroporation has several drawbacks and is not well-suited for producing optimal transfer efficiency.

[0028] Therefore, this paper provides a technique for transferring therapeutic materials into the cells of a recipient using “dynamic electroporation.” According to the dynamic electroporation technique proposed herein, a “dynamic” (i.e., moving) electroporation electric field is generated via one or more electroporation electrodes that move through a spatial region within, near, or adjacent to the target tissue (cells) in the recipient’s body (collectively and typically referred to as the “nearby spatial region”). However, according to the dynamic electroporation technique proposed herein, the trajectory (e.g., center point) of the dynamic electroporation electric field generated by delivering a series of electroporation signals to the electroporation electrodes varies over time. That is, the physical location of the trajectory of the dynamic electroporation electric field is time-varying and typically advances through a spatial region within the recipient’s body.

[0029] In some embodiments proposed herein, the time-varying position of the trajectory of the dynamic electroporation electric field is a result of the movement of the electroporation electrode within the spatial region of the receiver. That is, the change in the position of the trajectory of the dynamic electroporation electric field corresponds to a change in the physical positioning of the electroporation electrode used to generate the dynamic electroporation electric field.

[0030] Typically, dynamic electroporation induces electroporation of cell populations adjacent to the spatial region through which the electroporating electrode moves (e.g., cells adjacent to the length of the path / track of the moving electrode). That is, compared to conventional static electroporation techniques (e.g., techniques using fixed electrode arrays with multiple electrode pairs (e.g., anodes and cathodes) and complex setups), dynamic electroporation can be used to transfer therapeutic material along the electrode path into cells and can target a greater number of cells. Therefore, compared to static electroporation, dynamic electroporation allows for the electroporation of larger cell populations without increasing electrode size, electric field strength, or the number of electrodes, and potentially in a shorter time period. Dynamic electroporation can electroporate large areas with a single pair of electrodes compared to conventional static electroporation techniques, which is a simpler setup capable of achieving the same or even higher total number of electroporated cells. This results in increased yield and less damage to cells.

[0031] As used herein, dynamic electroporation is delivered via one or more electroporation electrode contacts (electroporation electrodes) disposed within (e.g., located within / on) a carrier component. The electroporation electrodes are electrically connected to an external current source (e.g., a current source located outside the recipient's body) that generates the electroporation current signal, sometimes referred to herein as an "electroporation device." The electroporation electrodes and the external current source are sometimes collectively referred to as a dynamic electroporation subsystem. As further described below, dynamic electroporation can be delivered via a separate dynamic electroporation subsystem (e.g., a dynamic electroporation subsystem separate from the implantable medical device) or via a dynamic electroporation subsystem integrated with the implantable medical device.

[0032] The dynamic electroporation electrodes according to embodiments presented herein are configured / arranged such that an external electroporation device delivers periodic current pulses to the electroporation electrodes as the carrier member moves through a spatial region near target tissue within the recipient's body. In some embodiments, electroporation is performed when the electroporation electrodes move from a proximal position (e.g., a position relatively closer to the recipient's body) toward a distal position (relatively farther from the recipient's body), or in other words, when the electroporation electrodes move from the insertion point / position toward the final / destination point / position. In some embodiments, electroporation is performed when the electroporation electrodes move from a distal position toward a proximal position, or in other words, when the electroporation electrodes move from the final / destination point / position toward the insertion point / position. In still other embodiments, electroporation is performed when the electroporation electrodes move from a proximal position toward a distal position and when the electroporation electrodes move from a distal position toward a proximal position. In other words, dynamic electroporation can be performed while the carrier component is being inserted (i.e., when the carrier component moves from the insertion point to the destination point) and / or while the carrier component is being removed / retracted (i.e., when the carrier component moves from the destination point to the insertion point).

[0033] As described above, a dynamic electroporation electric field is used to open pores in the cell membrane, allowing therapeutic materials to enter the cell. That is, a dynamic (moving) electroporation electric field is generated by delivering periodic current pulses to the electroporation electrode as it moves through a spatial region, wherein the position of the electric field trajectory changes over time. Due to the time-varying position of the dynamic electroporation electric field trajectory, cells along the insertion path (adjacent to the spatial region) experience a sufficiently high electric field intensity to create pores in the cell membrane, thereby maximizing the number of cells taking up the therapeutic material. Therefore, the therapeutic material is introduced into the vicinity of the cell to be electroporated before (before) the delivery of the dynamic electroporation electric field. In some embodiments, a solution containing the therapeutic material to be transferred to the cell is pumped into a spatial region near the target tissue (e.g., into the cochlea) as the electroporation carrier component is moved.

[0034] As described above, in some embodiments, the electroporation subsystem provided herein can operate as a standalone device (e.g., not part of an implantable medical device). However, in other embodiments, the electroporation subsystem provided herein can be part of an implantable medical device (e.g., partially or fully integrated therein). Several types of implantable medical devices exist that deliver stimulation signals (current signals) to compensate for the recipient's defects. For ease of illustration only, the embodiments presented herein are described primarily with reference to one type of implantable medical device (i.e., a cochlear implant system). However, it should be understood that the techniques provided herein can also be used with a variety of other implantable medical devices and / or systems. For example, the techniques presented herein can be used with other auditory prosthetic systems, including middle ear auditory prosthetic systems (middle ear implant systems), bone conduction device systems, direct acoustic stimulator systems, electro-acoustic prosthetic systems, and auditory brain stimulator systems. wait The techniques provided herein can also be used with systems that include or include the following: tinnitus treatment devices, vestibular devices (e.g., vestibular implants), visual devices (i.e., bionic eyes), sensors, pacemakers, drug delivery systems, including those for delivering DNA vaccines and / or other compounds (e.g., cisplatin for electrochemical therapy). wait Systems / devices, defibrillators, functional electrical stimulation devices, catheters, epilepsy devices (e.g., devices for monitoring and / or treating epileptic events), sleep apnea devices, electroporation devices. wait .

[0035] Figure 1A This is a schematic diagram of an exemplary cochlear implant system 100 configured to implement aspects of the techniques proposed herein, namely, configured to perform dynamic electroporation. Figure 1BThis is a block diagram of the cochlear implant system 100. For ease of explanation, it will be described together. Figure 1A and Figure 1B .

[0036] The cochlear implant system 100 includes an external component 102 and an internal / implantable component 104, sometimes referred to as the "cochlear implant 104". The external component 102 is attached directly or indirectly to the recipient's body and typically includes an external coil 106 and a magnet typically fixed relative to the external coil 106. Figure 1A (Not shown in the image). External component 102 also includes one or more input elements / devices 113 for receiving input signals at the sound processing unit 112. In this example, one or more input devices 113 include sound input devices 108 configured to capture / receive input signals (e.g., a microphone positioned by the receiver's auricle 110, a pickup coil). wait One or more auxiliary input devices 109 (e.g., audio ports such as Direct Audio Input (DAI), data ports such as Universal Serial Bus (USB) ports, cable ports) wait ) and a wireless transmitter / receiver (transceiver) 111, each located in, on or near the sound processing unit 112.

[0037] The sound processing unit 112 also includes, for example, at least one battery 107, a radio frequency (RF) transceiver 121, and a processing module 125. The processing module 125 may include multiple components, including a sound processor 131.

[0038] exist Figure 1A and 1B In the example, sound processing unit 112 is a behind-the-ear (BTE) sound processing unit configured to attach to and be worn adjacent to the recipient's ear. However, it should be understood that embodiments of the invention can be implemented using sound processing units with other arrangements, such as off-the-ear (OTE) sound processing units (i.e., components having a generally cylindrical shape and configured to be magnetically coupled to the recipient's head). wait Mini or micro BTE units, in-canal units configured to be located in the recipient's ear canal, and wearable sound processing units. wait .

[0039] Back Figure 1A and 1BAn exemplary embodiment of the implantable component (cochlear implant) 104 includes an implant body (main module) 114, a lead region 116, and an intracochlear stimulation assembly 118, all configured for implantation under the skin / tissue (tissue) 105 of the recipient. The implant body 114 typically includes a hermetically sealed housing 115, in which RF interface circuitry 124 and a stimulator unit 120 are disposed. As further described below, the stimulator unit 120 includes stimulation electronics 133. Stimulation electronics 133 includes one or more current sources on an integrated circuit (IC) and other components. The implant body 114 also includes an internal / implantable coil 122, which is typically outside the housing 115 but connected via a hermetically sealed feedthrough (…). Figure 1B (Not shown) is connected to RF interface circuit 124.

[0040] As described above, the stimulation component 118 is configured to be at least partially implanted in the cochlea 137 of a recipient. The stimulation component 118 includes a carrier member 127 and a plurality of longitudinally spaced intracochlear electrodes 126 disposed in / on the carrier member 127. The intracochlear electrodes 126 collectively form a contact or electrode array 128 configured to deliver an electrical stimulation signal (current signal) to and / or absorb a stimulation signal from the recipient's cochlea. Figure 1A A particular arrangement is shown, wherein the stimulation assembly 118 includes twenty-two (22) intracochlear electrodes 126, labeled electrodes 126 (1) to 126 (22). It should be understood that the embodiments presented herein can be implemented in alternative arrangements with different numbers of intracochlear electrodes.

[0041] Stimulation component 118 extends through an opening in the recipient's cochlea (e.g., cochleostomy, round window). wait ), and has via lead area 116 and airtight feeder ( Figure 1B (Not shown) is connected to the proximal end of the stimulator unit 120. The lead region 116 includes a plurality of conductors (wires) that electrically connect the electrode 126 to the stimulator unit 120.

[0042] exist Figure 1A The diagram also shows an external cochlear electrode 126 (23). The external cochlear electrode 126 (23) is an electrode contact configured, for example, to deliver electrical stimulation to and / or absorb current from the cochlea of ​​a recipient. The external cochlear electrode 126 (23) is connected to a reference lead 123 comprising one or more conductors that electrically couple the external cochlear electrode 126 (23) to the stimulator unit 120.

[0043] As further described below, the intracochlear electrodes 126(1)-126(22) and the external cochlear electrode 126(23) can be used postoperatively to stimulate the recipient's cochlea 137 (i.e., as a pathway for the delivery or return of electrical signals to or from the cochlea 137), which elicits auditory perception. Thus, for ease of description, the intracochlear electrodes 126(1)-126(22) and the external cochlear electrode 126(23) are sometimes referred to herein as "stimulation electrodes".

[0044] Figure 1A and 1B The stimulation assembly 118 is also shown to include two (2) electrode contacts (electrodes) 150 (1) and 150 (2). As further described below, electrodes 150 (1) and 150 (2) are electrically connected to an external electroporation device 160 via electroporation leads 162 (e.g., one or more wires). Figure 1B (As shown in the diagram). As described elsewhere herein, electrodes 150(1) and 150(2) can be used to electroporate the cochlear nerve cells of the recipient during the implantation of the stimulation assembly 118 into the cochlea 137. That is, electrodes 150(1) and 150(2) can be configured to provide, absorb, or provide and absorb an electroporation signal (generated by an external electroporation device 160) that causes a dynamic electroporation electric field to be applied to the nerve cells of the cochlea 137. Thereafter, electrodes 150(1) and 150(2) can be electrically isolated (e.g., electrically disconnected) from the external electroporation device 160. Although shown as two electrodes located at the distal end 159 of the stimulation assembly 118, more than two electrodes may be present and used for electroporation.

[0045] As described elsewhere herein, electrodes configured to perform electroporation, such as electrodes 150(1) and 150(2), are referred to herein as “electroporation electrodes.” Electroporation electrodes 150(1) / 150(2) and external electroporation device 160 are collectively referred to herein as the “dynamic electroporation subsystem” 164. Figure 1A and 1B In one embodiment, the dynamic electroporation system 164 is referred to as being integrated with the cochlear implant system 100.

[0046] exist Figure 1A and 1BIn the embodiment, the electroporation electrodes 150(1) and 150(2) are structurally different from the cochlear electrodes 126(1)-126(22) in that the electroporation electrodes are not connected to the stimulator unit 120 (while the cochlear electrodes 126(1)-126(22) must be connected to the stimulator unit 120 to perform their operation). In particular, the high voltage associated with electroporation would damage the stimulator unit 120, therefore, the electroporation electrodes 150(1) and 150(2) are electrically isolated from the stimulator unit 120. It is also concluded that the cochlear electrodes 126(1)-126(22) cannot be used to perform electroporation due to the electrical connection between the cochlear electrodes 126(1)-126(22) and the stimulator unit 120.

[0047] As mentioned above, in Figure 1A and 1B In the example, electroporation electrodes 150(1) and 150(2) are electrically connected to an external electroporation device 160. However, in some alternative embodiments, the stimulator unit 120 may be designed to generate and process larger electroporation voltages. Thus, in such an embodiment, the electroporation electrodes 150(1) and 150(2) may be connected to the stimulator unit 120, which in turn includes an electroporation signal generator for generating and delivering electroporation signals (e.g., without needing to be connected to an external source to generate the electroporation signal). This arrangement in Figure 6 As shown in the image.

[0048] More specifically, Figure 6 It shows something that is basically similar to Figure 1A-1B The cochlear implant system 100 is a cochlear implant system 600. However, in this example, the implantable component includes a stimulator 620 designed to generate and process larger electroporation voltages. For this purpose, the stimulator unit 620 includes an onboard electroporation signal generator 660. The electroporation electrodes 150(1) / 150(2) and the onboard electroporation signal generator 660 are collectively referred to herein as the “dynamic electroporation subsystem” 664. Figure 6 In one embodiment, the dynamic electroporation system 664 is referred to as being integrated with the cochlear implant system 600.

[0049] Electroporation can serve many relevant purposes. In some examples, electroporation is used to open pores in cells in the presence of a therapeutic material containing / including a therapeutic agent, so that an effective amount of the therapeutic agent can enter the electroporated (open) cell. As used herein, the term "therapeutic agent" can include, but is not limited to, biological or bioactive substances, chemicals, pharmaceuticals, nanoparticles, ions, including nucleic acids (e.g., deoxyribonucleic acid (DNA), DNA cassettes, cDNA or plasmids, ribonucleic acid (RNA) molecules, RNAi, etc.), proteins, peptides (e.g., brain-derived neurotrophic factor, etc.), hormones, etc. Therefore, according to some embodiments, the therapeutic agent can be delivered to the cochlea 137 before electroporation. Such a therapeutic agent can be delivered in a variety of different ways, such as via implantation tools, material delivery devices (e.g., lumen, syringe). wait The cavity inside the carrier component 127 and the coating on the carrier component 127 wait .

[0050] As noted, the cochlear implant system 100 includes an external coil 106 and an implantable coil 122. Coils 106 and 122 are typically linear antenna coils, each comprising multiple turns of electrically insulated single-strand or multi-strand platinum or gold wire. Generally, a magnet is fixed relative to each of the external coil 106 and the implantable coil 122. The magnet fixed relative to the external coil 106 and the implantable coil 122 facilitates operational alignment between the external coil and the implantable coil. This operational alignment of coils 106 and 122 enables the external component 102 to transmit data and, possibly, power to the implantable component 104 via a tightly coupled wireless link formed between the external coil 106 and the implantable coil 122. In some examples, the tightly coupled wireless link is a radio frequency (RF) link. However, various other types of power transfer, such as infrared (IR), electromagnetic, capacitive, and inductive transfer, can be used to transfer power and / or data from the external component to the implantable component, and thereby, Figure 1B Only one example layout is shown.

[0051] As described above, the sound processing unit 112 includes a processing module 125. The processing module 125 is configured to convert an input audio signal into a stimulation control signal 136 for stimulating a receiver's first ear (i.e., the processing module 125 is configured to perform sound processing on the input audio signal received at the sound processing unit 112). In other words, the sound processor 131 (e.g., implementing firmware, software) waitOne or more processing elements are configured to convert the captured input audio signal into a stimulus control signal 136 representing a stimulus signal to be delivered to a receiver. The input audio signal processed and converted into a stimulus control signal may be an audio signal received via a sound input device 108, a signal received via an auxiliary input device 109, and / or a signal received via a wireless transceiver 111.

[0052] exist Figure 1B In one embodiment, a stimulation control signal 136 is provided to an RF transceiver 121, which transceivers transmit the stimulation control signal 136 (e.g., in an encoded manner) percutaneously to the implantable component 104 via an external coil 106 and an implantable coil 122. That is, the stimulation control signal 136 is received at an RF interface circuit 124 via the implantable coil 122 and provided to the stimulator unit 120. The stimulator unit 120 is configured to use the stimulation control signal 136 to generate a stimulation signal (e.g., an electrical signal) for delivery to the recipient's cochlea via one or more stimulation electrodes 126(1)-126(22). In this manner, the cochlear implant system 100 electrically stimulates the recipient's auditory nerve cells, bypassing the missing or defective hair cells that typically convert sound vibrations into neural activity in a manner that would otherwise enable the recipient to perceive one or more components of an input audio signal.

[0053] Due to the constrained bone structure of the cochlea, the insertion of the stimulating electrode array is relatively easy, safe, and provides a stable body-implant interface, all of which contribute to the success of cochlear implants. Furthermore, advanced mechanical design offers minor performance improvements. However, one of the key performance limiting factors in conventional cochlear implants is the distance between the stimulating electrodes within the cochlea and the corresponding stimulated spiral ganglion cells. Reducing this distance could, for example, create additional stimulation sites that could deliver better frequency discrimination to the recipient, enabling the use of lower stimulation currents and thus reducing implant power consumption, and / or enabling the use of lower stimulation voltages and thus reducing implant size and power consumption. It has been proposed to inject nerve growth factor into the cochlea during surgery to induce nerve growth toward the stimulating electrodes. However, injected nerve growth factor typically dissipates before any significant benefit is obtained. One possible solution to this critical problem is to insert the nerve growth factor gene into the cells of the cochlea via cell electroporation during surgical implantation of the intracochlear stimulation component.

[0054] As described above, electroporation refers to applying an electric field to a cell, causing pores to open in the cell membrane. When these cells open in the presence of a therapeutic agent (such as the nerve growth factor gene), the therapeutic agent can enter the cell through the cell membrane. After the potential is removed, the pores in the cell membrane close, allowing the therapeutic agent to remain in the cell.

[0055] As mentioned above, successful electroporation requires exposing cells to an electric field using a voltage sufficient to create pores in the membrane. This paper presents a technique that enables electroporation of cells (e.g., cochlear nerves) along a pathway intended for cochlear implantation by applying a dynamic electroporation electric field.

[0056] More specifically, see reference Figure 1A and 1B The electroporation electrodes 150(1) and 150(2) are electrically connected to an external electroporation device 160 via an electroporation lead 162. The electroporation electrodes 150(1) and 150(2) are used to perform dynamic electroporation on the recipient's cochlear nerve cells during the implantation of the stimulation assembly 118 into the cochlea 137 (i.e., while the electrode assembly 118 is inserted into the cochlea 137). In some examples, the electroporation electrodes 150(1) and 150(2) are positioned at the distal end 159 of the carrier member, allowing a lower voltage to be supplied to the electroporation electrodes along the path, thereby allowing a sufficient number of cells to be transferred.

[0057] Figure 1A and 1B An arrangement of external components is shown for a cochlear implant system 100. As described elsewhere herein, it should be understood that embodiments of the invention can be implemented in cochlear implant systems with alternative arrangements and / or in other types of implantable medical devices. As mentioned above, for ease of description only, the techniques presented herein are described primarily with reference to cochlear implant systems. However, it should be understood that the techniques presented herein can also be used with a variety of other implantable or non-implantable medical devices and related medical device systems. For example, the techniques presented herein can be used with other auditory prosthesis systems, including middle ear auditory prosthesis systems (middle ear implant systems), bone conduction device systems, direct acoustic stimulator systems, electro-acoustic prosthesis systems, and auditory brain stimulator systems. wait The techniques presented herein can also be used with systems that include or include the following: tinnitus treatment devices, vestibular devices (e.g., vestibular prostheses), visual devices (i.e., bionic eyes), sensors, pacemakers, drug delivery systems, including devices for delivering vaccines, chemotherapy, etc. (e.g., without leaving a device in the body), defibrillators, functional electrical stimulation devices, catheters, seizure devices (e.g., devices for monitoring and / or treating epileptic events), sleep apnea devices, and electroporation devices. wait However, for ease of description only, further details of the techniques presented herein will generally be described with reference to cochlear implant systems.

[0058] As described above, some embodiments presented herein may use electrodes that are dedicated solely to electroporation (i.e., electroporation electrodes), as well as intracochlear electrodes and one or more extracochlear electrodes (collectively, stimulating electrodes that can be used postoperatively to stimulate the recipient's cochlea). Also as described above, the electroporation electrode may be integrated into the same carrier member (e.g., silicone or elastomer) as the intracochlear electrode. Integrating the electroporation electrode into the same carrier member as the intracochlear electrode allows the geometry (and thus the electric field controlling the electroporation process) to be clearly defined during electroporation. However, in other embodiments, the electroporation electrode may be physically separated from the carrier member in which the intracochlear electrode is disposed (e.g., a portion of the insertion tool, the separated electrode). wait The above is referred to as the "independent dynamic electroporation subsystem". Figure 2A , 2B Figures 2C and 2C illustrate an embodiment of such a standalone dynamic electroporation subsystem according to the proposed embodiments.

[0059] More specifically, Figure 2A This is a schematic diagram of an independent dynamic electroporation subsystem 264 according to certain embodiments presented herein, and Figure 2B and 2C This is a diagram showing the independent electroporation subsystem 264 partially inserted into the cochlea 237 of the recipient. For ease of description, it will be described together. Figure 2A-2C .

[0060] As shown in the figure, the independent dynamic electroporation subsystem 264 includes a carrier component (carrier component 227) and two electroporation electrode contacts (electrodes) 250(1) and 250(2) positioned / set in / on the carrier component. Figure 2A-2C In a specific example, electroporation electrodes 250(1) and 250(2) are positioned at the distal end (tip) 259 of carrier member 227. Electroporation electrodes 250(1) and 250(2) are electrically connected to an external electroporation device 260 configured to generate an electroporation signal (current signal) to be delivered via electroporation electrodes 250(1) and 250(2). More specifically, in this example, carrier member 227 includes two isolated electrical conductors (e.g., wires) 268(1) and 268(2), each of which terminates at one of the electroporation electrodes 250(1) and 250(2). Electrical conductors 268(1) and 268(2) extend through electroporation lead 262 to electroporation device 260.

[0061] As described above, in order to perform dynamic electroporation, the treatment is introduced near the cells to be electroporated before (before) the delivery of the dynamic electroporation electric field. Therefore, in Figure 2A-2CIn some embodiments, the dynamic electroporation subsystem 264 includes a therapeutic material delivery device 270. In these embodiments, as the carrier member 227 moves through the cochlea, a solution containing therapeutic material to be transferred to the cochlear cells is pumped into a spatial region near the target tissue (e.g., into the cochlea 237). More specifically, the therapeutic material delivery device 270 is fluidly coupled to the proximal end 271 of an elongated cannula 272 extending longitudinally through the carrier member 227. The cannula 272 has a distal opening 273 located at the distal end 259 of the carrier member 227 (e.g., for supplying the therapeutic material to be transferred to the cells).

[0062] The therapeutic material delivery device 270 can be electrically operated (e.g., via a pump, pressurized reservoir). wait (or it can be manually operated (e.g., syringe, manual pump)) wait This device supplies a solution containing therapeutic material to be transferred into cells. The flow rate of the fluid delivery device can be set to a constant or variable rate to ensure that an effective amount of therapeutic agent is delivered to the appropriate location for electroporation.

[0063] As described above, according to the dynamic electroporation technique proposed herein, electroporation electrodes 250(1) and 250(2) generate a dynamic electroporation electric field as they move through a spatial region near the target tissue (cells) within the recipient's body. Figure 2A-2C In the example, the spatial region near the target is the cochlea 227. During dynamic electroporation, when the carrier member 227 is inserted, retracted, or inserted and retracted into the cochlea, it can be repeatedly and periodically induced via electroporation electrodes 250(1) and 250(2). wait Electroporation signals are delivered. As a result, electroporation will occur along the entire length of the cochlea (at different time points during insertion). Figure 2B In the example, dynamic electroporation is performed simultaneously with the insertion of the carrier member 227 into the cochlea 237 (as the carrier member moves from the insertion point to the destination point), while... Figure 2C In the example, dynamic electroporation is performed while the carrier member 227 is removed / retracted into the cochlea 237 (i.e., when the carrier member moves from the destination point to the insertion point).

[0064] As mentioned above, in Figure 2A-2CIn one embodiment, two electroporation electrodes 250(1) and 250(2) are positioned at the distal end (tip) 259 of the carrier member 227. As also stated above, it should be understood that the use of two electroporation electrodes is merely illustrative, and in other embodiments, four, six, eight, ten, or more electrodes may be positioned in / on the carrier member 227. In some embodiments, the electroporation electrodes are arranged near or beginning near the distal end 259 to enable electroporation of the cells along a path of movement. However, in other embodiments, the electroporation electrodes may be arranged in other areas of the carrier member 227.

[0065] In some cases, multiple electroporation electrodes can be arranged as multiple different anode / cathode pairs. Using multiple different anode / cathode pairs during dynamic electroporation allows for the delivery of different electroporation pulses at each pair. Applying pulses with different properties can be beneficial, such as increased voltage or amplitude, altered polarity, etc., so that as the array moves, the cells undergo trajectories of increased (or decreased) field strength and altered orientation. Such changes in field orientation can be beneficial to the electroporation process, for example, increasing the number of electroporated cells. Alternating voltage amplitude and polarity of the electroporation pulses can also be achieved using a single electrode pair.

[0066] Figure 3A , 3B Examples 3A, 3B, and 3C are a series of schematic diagrams illustrating dynamic electroporation of a recipient cell 374 according to embodiments provided herein. In examples 3A, 3B, and 3C, a carrier member 337 includes two electroporation electrodes 350(1) and 350(2), and dynamic electroporation is performed while the carrier member 337 is inserted (moved in the distal direction) through a spatial region near the cell 374.

[0067] Figures 3A-3C This illustrates that when the carrier member 327 is inserted (i.e., moved in the distal direction) into the spatial region, the therapeutic material 375 is introduced into the spatial region near the cell 374. Specifically, Figures 3A-3C The electroporation electrode is shown being gradually inserted into the scala turcica or other spatial region adjacent to the recipient's cell 374. Figures 3A-3C The electroporation signal delivered to cells 374 is also schematically shown at 377, enabling the transfer of therapeutic material 375 to those cells.

[0068] exist Figures 3A-3C In one embodiment, the electroporation signal 377 is delivered by a pair of electroporation electrodes 350(1) and 350(2) disposed at the distal end of the carrier member 327. As a result, cells 374 adjacent to the movement path of the carrier member 327 are electroporated along the length of the insertion path of the carrier member 327.

[0069] Typically, the electroporation signal 377 comprises a current waveform of sufficient magnitude / amplitude and duration to form a pore in the cell membrane. Suitable waveform shapes include, but are not limited to, square pulses, exponentially decaying pulses, step pulses, ramp pulses, and alternating polarity pulses. wait The electroporation signal 377 may include, for example, a monopole pulse or a biphasic pulse. wait Furthermore, the electroporation signal 377 can be formed by any suitable number of pulses, including two, three, four, five, six, seven, eight, nine, ten, fifteen, twenty, or more pulses. However, by minimizing the number of electroporation electrodes, damage to cells from high fields can also be minimized. Using fewer electrodes and by dynamically moving the electrodes along the path, smaller fields can be generated, and electroporation can still be performed efficiently. That is, compared to performing electroporation using a large field (as in a conventional static arrangement), dynamic electroporation uses a series of smaller fields during the travel / movement of the carrier component, and therefore, cells near the electroporation electrodes may experience fewer damaging conditions during electroporation (when compared to the damage that occurs when performing electroporation using a large field).

[0070] The properties of the electroporation signal 377 can vary depending on the cell type performing the electroporation. For example, electroporation in the cochlea may require higher voltages and different pulse rates than for other applications, such as nerve stimulation of the spinal cord. wait In some respects, lower currents can be used for electroporation because the cells can be subjected to repetitive pulses as the electroporation electrode moves along a path adjacent to the cell.

[0071] Typically, dynamic electroporation involves applying a regular (e.g., continuous, periodic) force to the cell 374 via electroporation electrodes 350(1) and 350(2) as the carrier member 327 moves along a path adjacent to the cell 374 to be electroporated. wait The cell 374 can form tissue, organ, or other structure in the recipient. In some aspects, the movement of the carrier member 327 may include continuous movement along a path or a series of discrete positions (e.g., where the electroporation electrode tip moves along the path and pauses at a series of positions), wherein one or more pulses are applied in a stepwise manner at each position.

[0072] In the embodiments provided herein, such as Figure 3A and 3BAs shown, two electroporation electrodes can be used for dynamic electroporation of cell populations adjacent to the spatial region through which the electroporation electrodes move (e.g., cells adjacent to the length of the path / track of the moving electrodes). Although embodiments illustrating electroporation associated with directionality have been presented, these techniques can be used for any directionality, including insertion, removal / retraction, or combinations thereof. These techniques can be performed during multiple rounds of insertion and retraction.

[0073] As described above, before delivering the electroporation signal 377 to the cell 374, the therapeutic material 375 is introduced into the spatial region, or at least close to the cell to be electroporated. As described above, the therapeutic material 375 can be delivered in a variety of different ways, and the therapeutic material 375 can have a variety of different forms and / or properties. In some aspects, the therapeutic material may include a therapeutic agent. The therapeutic agent may include biological or bioactive substances, chemicals, pharmaceuticals, nanoparticles, ions, including nucleic acids (e.g., deoxyribonucleic acid (DNA), DNA cassettes, cDNA or plasmids, ribonucleic acid (RNA) molecules, RNAi, etc.), proteins, peptides (e.g., brain-derived neurotrophic factor). wait These include hormones, etc., or other agents that can be used to prevent or treat diseases or conditions of the inner ear. In some respects, therapeutic agents that can be used to prevent or treat conditions or diseases of the inner ear can be transferred into cells using the techniques provided herein. The therapeutic agents can be suspended or dissolved in any suitable liquid (e.g., water, saline solution). wait A solution is formed in the solution. Typically, the solution will have a conductivity level suitable for performing electroporation.

[0074] Any suitable device can be used (e.g., needle, syringe, cannula, catheter, capillary). wait The solution containing a therapeutic agent or other therapeutic material is injected into the perilymph or other structures, and can be injected simultaneously with, before, or after the insertion or retraction of the carrier member 327. For example, in some embodiments, the therapeutic material can be delivered via a cannula inside the carrier member 327, delivered via a separate delivery device, or released from the carrier member 327 (e.g., eluted from silicone rubber). wait Released from the excipient fixed on the carrier member 327, such as from the hydrogel (e.g., pluronic) or hyaluronic acid (e.g., Healon). wait ), film-forming systems (e.g., Unisun's PVA with nanoparticles) wait ), biodegradable matrices (e.g., PLGA) wait ), pellets (e.g., O-Ray) wait ), nanoparticles wait release.

[0075] In some embodiments, portions of the electroporation electrodes 350(1) and 350(2) or the carrier member 327 are configured to form a seal with the walls of a spatial region (e.g., a drum-like structure) through which the carrier member 327 moves. In such embodiments, therapeutic material is introduced into this sealed volume such that the therapeutic material is not diluted by the recipient's bodily fluids.

[0076] In some embodiments, portions of the electroporation electrodes 350(1) and 350(2) or the carrier member 327 may expand to form a seal, bringing the electroporation electrodes 350(1) and 350(2) into direct contact with the cell 374. This direct contact improves electroporation efficiency. In such embodiments, contact pressure and material properties are selected to prevent mechanical damage to the cell during movement of the carrier member 327. In some such embodiments, stepwise dynamic electroporation may be performed, wherein the carrier member 327 is positioned at a series of locations along a path. In this case, the carrier member 327 moves to a first location and expands to form a seal, where the electrode contacts are in direct contact with the cell. Electroporation is performed at this first location, and the carrier member 327 subsequently contracts to remove the seal. The carrier member 327 is then moved to a second location, and the above steps are repeated. The process may be performed iteratively at multiple different locations. This arrangement in Figure 7A and 7B As shown in the image.

[0077] More specifically, Figure 7A and 7B A carrier member 727 is shown, comprising two electroporation electrodes 750(1) and 750(2) and a sleeve 772. An expandable portion 751(1) is disposed adjacent to the electroporation electrode 750(1), and an expandable portion 751(2) is disposed adjacent to the electroporation electrode 750(2). Figure 7A As shown, both the expandable portions 751(1) and 751(2) have a first (non-expandable) arrangement / configuration to facilitate the insertion and movement of the carrier member 727. However, as Figure 7B As shown, both expandable portions 751(1) and 751(2) have a second (expansion) arrangement / configuration, which is configured to form a seal with the wall of the spatial region (e.g., a drum step) through which the carrier member 727 moves. Figure 7B In the second arrangement, a therapeutic material can be introduced via a sleeve 772, and the therapeutic material will be sealed within a volume defined by expandable portions 751(1) and 751(2), which includes electroporation electrodes 750(1) and 750(2). Figure 7C As shown, the electroporation electrode 750 (1) may or alternatively be located within the expandable portion 751 (1), and the second electrode 750 (2) is located within the second expandable portion 751 (2) to make the electrode contact the wall of the space region (e.g., cells lining the inner wall of the scute).

[0078] In other respects, space-filling and / or soft electrodes can be used to form a seal between the electroporation electrode and the walls of the space region (e.g., a dura mater). This method allows the electroporation electrode to be positioned and a solution containing therapeutic material to be delivered into the region formed by the seal. Therefore, the therapeutic material remains close to the cell during electroporation. Examples include conductive hydrogels (e.g., conductive hydrogels for medical applications, including CPs (e.g., polypyrrole (PPy), polyaniline (PANI), polyethylenedioxythiophene (PEDOT))) and polysaccharides or proteins (e.g., alginate, gelatin / GelMA, collagen, chitosan). wait The composite material can be used to form electroporation electrodes 350(1) and 350(2) and can expand. A dehydrated conductive hydrogel can be provided as a coating on the two metal electrode contacts. Upon contact with perilymph, the hydrogel swells as it becomes more hydrated until it contacts the cell-covered spatial region. For example, co-electrochemical deposition of PEDOT and alginate hydrogels on electrode contacts of multichannel medical devices (e.g., BT PEG-GelDOT coating and BT PEDOT-PSS (BTPP) coating). wait When hydrated, the electrode can expand to fill the gap between the electroporation electrode and the surface it is intended to contact. This method allows the electroporation electrode to be positioned in close contact with the target cell to be electroporated. Due to the material properties of the electroporation electrode and the low pressure applied to the cell, the electroporation electrode can be moved (e.g., inserted into or retracted from the cochlea) without damaging the cell it contacts.

[0079] In some embodiments, electrophysiological feedback can be used to control the insertion and / or retraction speed of the carrier component 327. For example, electrophysiological measurements include, but are not limited to, impedance measurements, neural response telemetry (NRT) measurements, and electrocochleography (EcochG) measurements. wait For example, impedance can be used as a form of surgical feedback to measure, confirm, and locate carrier component 327, and to determine whether carrier component 327 (or electrodes 350(1) / 340(2)) is in contact with cells. In some respects, electrophysiological feedback measurements can be performed using more than two electrodes.

[0080] For example, NRT and / or EcochG can be used to assess tissue health and / or damage to neural structures during insertion of the carrier component 327. In some respects, EcochG can be used in combination with the electroporation procedure described herein to prevent and / or minimize damage to the cochlear structures.

[0081] Figure 4This is a flowchart of method 490 according to some embodiments presented herein. Method 490 begins at 492, where a carrier member comprising a plurality of electroporation electrodes is inserted into a spatial region within the recipient's body. At 494, therapeutic material is introduced into the spatial region. At 496, dynamic electroporation is performed on a cell population positioned adjacent to the spatial region to transfer the therapeutic material into the cell population.

[0082] Figure 5 This is a flowchart of method 590 according to some embodiments presented herein. Method 590 begins at 592, wherein one or more electroporation electrodes are positioned in a spatial region adjacent to cells within the recipient's body. The one or more electroporation electrodes are electrically connected to an external electroporation device. At 594, therapeutic material is delivered into the spatial region. At 596, while simultaneously moving the one or more electroporation electrodes along a path through the spatial region, a series of current pulses are applied from the external electroporation device to the one or more electroporation electrodes to generate at least one dynamic electroporation electric field near the cells.

[0083] The advantages of this technique include, but are not limited to, electroporating higher volumes / numbers of cells, performing electroporation more uniformly along the path, performing electroporation with less damage to cells, and having a simpler setup, achieving the same or even better results as complex electrode arrays. Dynamic electroporation can also be beneficial when using a penetrating needle to electroporate cells along any injection path.

[0084] Example

[0085] An exemplary scheme for dynamic electroporation to electroporate cells within the scala tympani of the cochlea is provided. This scheme can be adapted to perform electroporation at other locations within the body and can be used in conjunction with other designs suitable for performing electroporation at other locations within the body.

[0086] Refer again Figure 2A -C, the carrier component 227 is inserted into the scala tympani of the cochlea 337 through a circular window membrane or cochlear insufflation, such as Figure 2B As shown in the figure. As described above, two electrode contacts 250(1) and 250(2) are connected to the electroporation device 260 to receive and deliver current signals for generating a dynamic electroporation electric field, and the sleeve 272 is fluidly coupled to the therapeutic material delivery device 270.

[0087] Following standard surgical procedures, the recipient's cochlea 237 is exposed and the carrier component 227 is positioned at the insertion point in the scala tympani. After the carrier component 227 reaches its final position (deepest or most distal insertion point), a solution containing the therapeutic material to be transferred to the recipient's target cells is injected using a cannula 272.

[0088] When the solution is introduced into the scala tympani, the volume of perilymph displaced by the inflow of the solution is achieved by ensuring that the displaced perilymph is released at the insertion point (e.g., the location where the carrier member 227 enters the scala tympani) without accumulating significant positive pressure within the scala tympani. In one aspect, the opening of the scala tympani is large enough to avoid forming a seal against the electroporation electrode, thus allowing the displaced perilymph to flow into the middle ear space. In this case, an injection solution containing the material to be electroporated displaces the perilymph into the middle ear space, immersing the cells of the scala tympani from the tip to the base of the electroporation electrode in a solution comprising the material to be electroporated. Therefore, during the movement of the electrode along the path, the perilymph is displaced by a material (e.g., a DNA solution) supplied at a selected rate through the cannula.

[0089] Subsequently, in order to electroporate the cells lining the scala tympani, which is directly adjacent to the electroporation electrodes 250(1) and 250(2), the electroporation device 260 is activated to appropriately deliver an electroporation signal (current pulse). Simultaneously with the delivery of the electroporation signal, the carrier member 227 is slowly retracted (e.g., by a surgeon using forceps, or by an electrically driven retractor). wait ), until the electroporation electrode is completely removed from the scala turcica. While the electroporation electrode is retracting, additional therapeutic material can be introduced into the scala turcica regularly or continuously. As a result, cellular electroporation can occur along the tracks of the two electroporation electrodes 250(1) and 250(2), wherein the tracks extend from the initial position of the tip 259 of the carrier member 327 to the insertion point of the scala turcica, as shown. Figure 2C The electroporation cells are shown in the figure.

[0090] It should be understood that the embodiments described above are not mutually exclusive, and various embodiments can be combined in various ways and arrangements.

[0091] The invention described and claimed herein is not limited in scope to the specific preferred embodiments disclosed herein, as these embodiments are intended to be illustrative and not to limit several aspects of the invention. Any equivalent embodiments are intended to be within the scope of the invention. In fact, various modifications to the invention will become apparent to those skilled in the art from the foregoing description, in addition to those modifications shown and described herein. Such modifications are also intended to fall within the scope of the appended claims.

Claims

1. A medical system comprising: A carrier component comprising multiple electroporation electrodes, wherein the carrier component is configured to be inserted into a spatial region within the body of a recipient; A therapeutic material delivery mechanism configured to introduce therapeutic material into the spatial region; as well as An electroporation device configured to activate the electroporation electrodes to dynamically electroporate a cell population located adjacent to the spatial region to transfer the therapeutic material into the cell population. In order to activate the electroporation electrodes to dynamically electroporate cell populations located adjacent to the spatial region, the electroporation device is configured as follows: As the carrier component moves along the path through the spatial region, a series of current pulses are delivered to the plurality of electroporation electrodes.

2. The system of claim 1, wherein, in order to activate the electroporation electrode to dynamically electroporate cell populations located adjacent to the spatial region, the electroporation device is configured as follows: Electroporation signals are delivered to the cell population via the plurality of electroporation electrodes to generate a dynamic electroporation electric field near the cell population using the plurality of electroporation electrodes, wherein the position of the trajectory of the dynamic electroporation electric field undergoes time-varying changes through the spatial region.

3. The system according to claim 2, The carrier component moves in a distal direction from a first position close to the external environment of the receiver to a second position away from the external environment to generate the time-varying position of the trajectory of the dynamic electroporation electric field through the spatial region.

4. The system according to claim 2, The time-varying change in the position of the carrier component moving in the proximal direction from a second position away from the external environment of the recipient to a first position closer to the external environment to generate the trajectory of the dynamic electroporation electric field through the spatial region.

5. The system according to claim 2, The electroporation signal comprises a series of biphase current pulses.

6. The system according to claim 1, The carrier component is manually moved along the path through the spatial region.

7. The system according to claim 1, The rate at which the carrier component moves through the spatial region varies at one or more locations within the spatial region.

8. The system of claim 7, wherein the spatial region is the scala tympani of the recipient's cochlea, and The rate at which the carrier component moves through the spatial region decreases near the location of the cochlea, which corresponds to one or more specific acoustic frequency ranges.

9. The system according to claim 1, wherein: The carrier component moves in a step-by-step manner along the path; and The electroporation device is configured to apply one or more current pulses at each of a plurality of discrete locations along the path.

10. The system according to claim 1, wherein: The carrier component moves continuously along the path; and The electroporation device is configured to periodically apply current pulses to the plurality of electroporation electrodes as the carrier member moves along the path.

11. The system according to claim 1, 2, 3 or 4, wherein the plurality of electroporation electrodes comprises two electroporation electrodes.

12. The system according to claim 1, 2, 3 or 4, wherein the plurality of electroporation electrodes are disposed at the distal end of the carrier member.

13. The system according to claim 1, 2, 3 or 4, further comprising: A stimulation assembly comprising multiple stimulation electrodes, the stimulation assembly being configured to be inserted into the spatial region after the carrier member has been removed from the spatial region, wherein the multiple stimulation electrodes are configured to deliver stimulation signals to the cell population of the recipient.

14. The system according to claim 1, 2, 3 or 4, The carrier component is configured to be inserted into the drum of the receiver.

15. The system according to claim 1, 2, 3 or 4, wherein The therapeutic material is introduced in the form of a solution comprising the therapeutic material.

16. The system according to claim 15, wherein: One or more of the plurality of electroporation electrodes, or one or more portions of the carrier member adjacent to one or more of the electroporation electrodes, are configured to contact the cells located adjacent to the spatial region to substantially seal the solution comprising the therapeutic material within the spatial region for a period of time.

17. The system of claim 15, wherein the therapeutic material delivery mechanism comprises an elongated sleeve extending along the length of the carrier member, and The solution is introduced into the spatial region via the elongated sleeve.

18. A medical system comprising: One or more electroporation electrodes, the one or more electroporation electrodes being configured to be positioned in a spatial region adjacent to cells in the body of a recipient, wherein the one or more electroporation electrodes are electrically connected to an electroporation device; A therapeutic material delivery mechanism configured to deliver therapeutic material, configured for transfer to the cells of the recipient, into the spatial region; as well as The electroporation device is configured to apply a series of current pulses to the one or more electroporation electrodes as the electrodes move along a path through the spatial region to generate at least one dynamic electroporation electric field near the cell and to transfer the therapeutic material into the cell.

19. The system according to claim 18, Within the recipient, the one or more electroporation electrodes move in a distal direction from a first proximal position within the spatial region to a second distal position to electroporate cells adjacent to the path.

20. The system according to claim 18, Within the recipient, the one or more electroporation electrodes move in a proximal direction from a second distal position within the spatial region to a first proximal position to electroporate cells adjacent to the path.

21. The system of claim 18, 19 or 20, wherein the one or more electroporation electrodes comprise a plurality of electroporation electrodes.

22. The system of claim 21, wherein the plurality of electroporation electrodes are disposed at the distal end of the carrier member.

23. The system according to claim 18, 19 or 20, wherein The series of current pulses includes a series of biphase current pulses to generate each dynamic electroporation field in the dynamic electroporation electric field.

24. The system according to claim 18, 19, or 20, wherein the electroporation device is configured to: Generate the series of current pulses; and The series of current pulses are provided to the one or more electroporation electrodes.

25. The system according to claim 18, 19 or 20, further comprising: A stimulation assembly comprising a plurality of stimulation electrodes, the stimulation assembly being configured to be inserted into the spatial region after one or more electroporation electrodes have been removed from the spatial region, wherein the plurality of stimulation electrodes are configured to deliver stimulation signals to the cells of the recipient.

26. The system according to claim 18, 19 or 20, wherein: The one or more electroporation electrodes move in a stepping manner along the path; and The electroporation device is configured to apply one or more current pulses at each of a plurality of discrete locations along the path.

27. The system according to claim 18, 19 or 20, wherein: The one or more electroporation electrodes move continuously along the path; and The electroporation device is configured to periodically apply current pulses to the electroporation electrodes as the one or more electroporation electrodes move along the path.

28. The system according to claim 18, 19 or 20, wherein The therapeutic material is delivered in the form of a solution comprising the therapeutic material.

29. The system of claim 28, wherein the one or more electroporation electrodes are embedded in the carrier member, and The one or more electroporation electrodes, or one or more portions of the carrier member adjacent to the one or more electroporation electrodes, are configured to contact the cells in the recipient's body to substantially seal the solution comprising the therapeutic material within the spatial region.

30. The system of claim 28, wherein the one or more electroporation electrodes are disposed in the carrier member, the therapeutic material delivery mechanism includes an elongated sleeve extending along the length of the carrier member, and wherein... The solution is delivered to the spatial region via the elongated sleeve.

31. The system according to claim 18, 19 or 20, wherein The one or more electroporation electrodes are configured to be positioned within the dura mater of the recipient.

32. A medical system comprising: A carrier component comprising multiple electroporation electrodes, wherein the carrier component is configured to be inserted into a spatial region within the body of a recipient; A therapeutic material delivery mechanism configured to introduce therapeutic material into the spatial region; as well as An electroporation device configured to deliver a series of electroporation signals to the electroporation electrodes to generate a dynamic electroporation electric field near the cells and transfer the therapeutic material into the cells while the carrier member moves through the spatial region, wherein the position of the trajectory of the dynamic electroporation electric field changes over time within the spatial region.

33. The system according to claim 32, wherein The carrier component moves in a distal direction from a first position close to the external environment of the receiver to a second position far from the external environment to generate a change in the position of the trajectory of the dynamic electroporation electric field through the spatial region.

34. The system according to claim 32, wherein The carrier component moves in the proximal direction from a second position away from the external environment of the recipient to a first position closer to the external environment to generate a change in the position of the trajectory of the dynamic electroporation electric field through the spatial region.

35. The system according to claim 32, 33 or 34, wherein: The carrier component is manually moved through the spatial region.

36. The system according to claim 32, 33 or 34, wherein: The rate at which the carrier component moves through the spatial region varies at one or more locations within the spatial region.

37. The system of claim 36, wherein the spatial region is the scala tympani of the recipient's cochlea, and wherein... The rate at which the carrier component moves through the spatial region decreases near the location of the cochlea, which corresponds to one or more specific acoustic frequency ranges.

38. The system according to claim 32, 33 or 34, wherein: The carrier component moves continuously along the path; and The electroporation device is configured to periodically apply current pulses to the plurality of electroporation electrodes as the carrier member moves along the path.

39. The system of claim 32, 33 or 34, wherein the plurality of electroporation electrodes comprises two electroporation electrodes.

40. The system according to claim 32, 33 or 34, wherein the plurality of electroporation electrodes are disposed at the distal end of the carrier member.

41. The system according to claim 32, 33 or 34, further comprising: A stimulation assembly comprising multiple stimulation electrodes is configured to be inserted into the spatial region after the carrier member has been removed from the spatial region, wherein the multiple stimulation electrodes are configured to deliver stimulation signals to a cell population of the recipient adjacent to the spatial region.

42. The system according to claim 32, 33 or 34, wherein The therapeutic material is introduced in the form of a solution comprising the therapeutic material.

43. The system of claim 42, wherein the therapeutic material delivery mechanism comprises an elongated sleeve extending along the length of the carrier member, and wherein... The solution is introduced into the spatial region via the elongated sleeve.

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