Therapeutic substance monitoring

Abstract

Presented herein are techniques for monitoring the state, amount, and / or concentration of a therapeutic substance in an implantable component, such as an implantable medical device. Specifically, the implantable component may include at least one therapeutic substance portion having a therapeutic substance therein for delivery to a recipient. The techniques presented herein measure an impedance across at least one therapeutic substance portion, and estimate a state, amount, and / or concentration of a therapeutic substance within the at least one therapeutic substance portion using the measured impedance.

Description

[0001] background Technical Field

[0002] The present invention generally relates to techniques for monitoring the state, amount and / or concentration of therapeutic substances. Background Art

[0003] Medical devices have provided a wide range of therapeutic benefits to recipients over the last several decades. Medical devices may include internal or implantable components / devices, external or wearable components / devices, or combinations thereof (e.g., devices having external components that communicate with implantable components). Medical devices, such as traditional 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.

[0004] Over the years, the types of medical devices and the range of functions performed by them 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 in a recipient's body. These functional devices are typically used to diagnose, prevent, monitor, treat, or manage disease / injury or its 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

[0005] In one aspect, a system is provided. The system includes: at least one therapeutic substance portion containing a therapeutic substance; and a measurement system configured to measure impedance across the at least one therapeutic substance portion and estimate a state of the therapeutic substance within the at least one therapeutic substance portion based on the measured impedance across the at least one therapeutic substance portion.

[0006] In another aspect, a method is provided. The method includes measuring impedance of at least one therapeutic substance portion containing a therapeutic substance; and estimating a state of the therapeutic substance within the at least one therapeutic substance portion based on the measured impedance.

[0007] In another aspect, one or more non-transitory computer-readable storage media are provided. The one or more non-transitory computer-readable storage media include instructions that, when executed by a processor, cause the processor to: obtain an impedance of at least one therapeutic substance portion; and estimate an amount of at least one therapeutic substance remaining in the at least one therapeutic substance portion based on the impedance of the at least one therapeutic substance portion.

[0008] In another aspect, a system is provided. The system includes: at least one therapeutic substance portion containing a therapeutic substance, the at least one therapeutic substance portion being configured to be implantable in a recipient's body; at least a first electrode and at least a second electrode, the at least first electrode and the at least second electrode being configured to be implanted in the recipient's body proximate to the therapeutic substance; a circuit system configured to measure impedance between the at least first electrode and the at least second electrode; and at least one processor configured to estimate a concentration of the therapeutic substance in the therapeutic substance portion from the measured impedance. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Embodiments of the present invention are described herein with reference to the accompanying drawings, in which:

[0010] Figure 1A is a schematic diagram illustrating a cochlear implant system with which aspects of the technology presented herein may be implemented;

[0011] Figure 1B It is wearable Figure 1A A side view of a recipient of a sound processing unit of a cochlear implant system;

[0012] Figure 1C yes Figure 1A A schematic diagram of components of a cochlear implant system;

[0013] Figure 1D yes Figure 1A Block diagram of a cochlear implant system;

[0014] Figure 2 is a schematic diagram showing a therapeutic substance portion and a measuring electrode according to certain embodiments presented herein;

[0015] Figure 3A , 3B , 3C and 3D are diagrams showing some embodiments according to the present invention. Figure 2 A series of schematic diagrams showing impedance changes of the therapeutic substance portion;

[0016] Figure 4 is a schematic diagram showing another therapeutic substance portion and measuring electrodes according to certain embodiments presented herein;

[0017] Figure 5 is an indication of how the impedance changes over time. Figure 4 a graphical representation of the state, amount and / or concentration of a therapeutic substance in a therapeutic substance portion of the apparatus;

[0018] Figure 6 is a schematic diagram showing a therapeutic substance portion in the form of a reservoir and a measuring electrode according to certain embodiments presented herein;

[0019] Figure 7 is a schematic diagram illustrating a measurement system according to certain embodiments presented herein;

[0020] Figure 8 is a flow chart illustrating an exemplary method for monitoring the state, amount, and / or concentration of a therapeutic substance in a therapeutic substance portion according to certain embodiments presented herein;

[0021] Fig. 9 is a flow chart illustrating another exemplary method for monitoring the state, amount, and / or concentration of a therapeutic substance in a therapeutic substance portion according to certain embodiments presented herein;

[0022] Fig.10 is a flow chart illustrating another exemplary method for monitoring the state, amount, and / or concentration of a therapeutic substance in a therapeutic substance portion according to certain embodiments presented herein;

[0023] Fig.11 is a flow chart illustrating yet another exemplary method for monitoring the state, amount, and / or concentration of a therapeutic substance in a therapeutic substance portion according to certain embodiments presented herein;

[0024] Fig.12 is a schematic diagram illustrating a vestibular stimulator system with which aspects of the technology presented herein may be implemented; and

[0025] Fig.13 is a schematic diagram illustrating a retinal prosthesis system with which aspects of the technology presented herein may be implemented. DETAILED DESCRIPTION

[0026] A growing area of ​​research and development involves the use of pharmaceutical compounds, biological substances, biologically active substances, etc., including pharmaceutical agents / active pharmaceutical ingredients (APIs), genes, messenger RNA (mRNA) or other signaling compounds that promote recovery and decomposition, chemicals, ions, drugs, etc., to treat various conditions in individual patients / recipients. These various substances (which are collectively referred to herein as "therapeutic substances") are delivered to induce some therapeutic result / treatment in the recipient. For example, therapeutic substances can be delivered to treat ear conditions (e.g., tinnitus, hearing loss, Meniere's disease, etc.), treat postoperative infections, fight cancer cells, treat neurodegenerative diseases, treat infectious diseases, regenerate neural tissue, etc.

[0027] Presented herein are techniques for monitoring the state, amount, and / or concentration of a therapeutic substance in an implantable component, such as an implantable medical device. Specifically, the implantable component may include at least one therapeutic substance portion having therein a therapeutic substance for delivery to a recipient. The techniques presented herein measure impedance across at least one therapeutic substance portion, and use the measured impedance to estimate the state, amount, and / or concentration of a therapeutic substance within at least one therapeutic substance portion.

[0028] For ease of description only, the technology presented herein is mainly described with reference to a specific implantable medical device system, i.e., a cochlear implant system. However, it should be understood that the technology presented herein can also be partially or completely implemented by other types of implantable medical devices. For example, the technology presented herein can be implemented by other auditory prosthesis systems including one or more other types of auditory prostheses (e.g., middle ear auditory prostheses, bone conduction devices, direct acoustic stimulators, electroacoustic prostheses, auditory brain stimulators, combinations or variations thereof, etc.). The technology presented herein can also be implemented by proprietary tinnitus treatment devices and tinnitus treatment device systems. In other embodiments, the technology presented herein can also be implemented by vestibular devices (e.g., vestibular implants), visual devices (i.e., bionic eyes), sensors, pacemakers, drug delivery systems, defibrillators, functional electrical stimulation devices, catheters, epileptic seizure devices (e.g., devices for monitoring and / or treating epileptic events), sleep apnea devices, electroporation devices, etc., or used in combination with them.

[0029] Figures 1A-1D An exemplary cochlear implant system 102 is shown with which aspects of the technology presented herein may be implemented. The cochlear implant system 102 includes an external component 104 / implantable component 112. Figures 1A-1D In the example of a cochlear implant, the implantable component is sometimes referred to as a "cochlear implant." Figure 1A The cochlear implant 112 is shown implanted in the recipient's head 154, while Figure 1Bis a schematic diagram of the outer member 104 worn on the head 154 of the recipient. Figure 1C is another schematic diagram of a cochlear implant system 102, and Figure 1D Additional details of cochlear implant system 102 are shown. For ease of description, the Figures 1A-1D .

[0030] Cochlear implant system 102 includes an external component 104 configured to be attached directly or indirectly to the body of a recipient, and an implantable component 112 configured to be implanted in the body of the recipient. Figures 1A-1D In the example of FIG. 1 , external component 104 includes a sound processing unit 106 , while cochlear implant 112 includes an implantable coil 114 , an implant body 134 , and an elongated stimulation assembly 116 configured to be implanted in the cochlea of ​​a recipient.

[0031] exist Figures 1A-1D In the example of the present invention, the sound processing unit 106 is an off-the-ear (OTE) sound processing unit (sometimes referred to herein as an OTE component) that is configured to send data and power to the implantable component 112. Generally speaking, the OTE sound processing unit is a component having a generally cylindrical housing 111 and configured to be magnetically coupled to the head of the recipient (e.g., including an integrated external magnet 150 configured to be magnetically coupled to an implantable magnet 152 in the implantable component 112). The OTE sound processing unit 106 also includes an integrated external (head component) coil 108 configured to be inductively coupled to the implantable coil 114.

[0032] It should be understood that the OTE sound processing unit 106 is merely illustrative of an external device that can operate with the implantable component 112. For example, in alternative examples, the external component can include a behind-the-ear (BTE) sound processing unit or a micro-BTE sound processing unit and a separate external component. Generally speaking, the BTE sound processing unit includes a housing that is shaped to be worn on the recipient's outer ear and connected to a separate external coil assembly via a cable, wherein the external coil assembly is configured to be magnetically coupled and inductively coupled to the implantable coil 114. It should also be understood that alternative external components can be located in the recipient's ear canal, worn on the body, etc.

[0033] As described above, cochlear implant system 102 includes sound processing unit 106 and cochlear implant 112. However, as further described below, cochlear implant 112 can operate independently of sound processing unit 106 for at least a period of time to stimulate a recipient. For example, cochlear implant 112 can operate in a first general mode (sometimes referred to as an "external listening mode"), in which sound processing unit 106 captures sound signals, which are then used as a basis for delivering stimulation signals to the recipient. Cochlear implant 112 can also operate in a second general mode (sometimes referred to as an "invisible hearing" mode), in which sound processing unit 106 cannot provide sound signals to cochlear implant 112 (e.g., sound processing unit 106 is not present, sound processing unit 106 is powered off, sound processing unit 106 is malfunctioning, etc.). Therefore, in the invisible hearing mode, cochlear implant 112 captures the sound signals itself via an implantable sound sensor, and then uses these sound signals as a basis for delivering stimulation signals to the recipient. Further details regarding the operation of cochlear implant 112 in the external listening mode are provided below, followed by details regarding the operation of cochlear implant 112 in the invisible listening mode. It should be understood that the reference to the external listening mode and the invisible listening mode is merely illustrative, and cochlear implant 112 may also operate in alternative modes.

[0034] exist Figure 1A and Figure 1C In the present invention, a cochlear implant system 102 is shown with an external device 110, which is configured to implement various aspects of the technology presented. The external device 110 is a computing device, such as a computer (e.g., a laptop, a desktop computer, a tablet computer), a mobile phone, a remote control unit, etc. As further described below, the external device 110 includes a telephone enhancement module, as further described below, which is configured to implement various aspects of the auditory rehabilitation technology presented herein for independent telephone use. The external device 110 and the cochlear implant system 102 (e.g., the OTE sound processing unit 106 or the cochlear implant 112) communicate wirelessly via a two-way communication link 126. The two-way communication link 126 may include, for example, short-range communication, such as a Bluetooth link, a Bluetooth low energy (BLE) link, a proprietary link, etc.

[0035] Return to Figures 1A-1DIn the example of the OTE sound processing unit 106, one or more input devices are configured to receive input signals (e.g., sound or data signals). The one or more input devices include one or more sound input devices 118 (e.g., one or more external microphones, audio input ports, telecoils, etc.), one or more auxiliary input devices 128 (e.g., audio ports, such as direct audio input (DAI), data ports, such as universal serial bus (USB) ports, cable ports, etc.), and wireless transmitter / receiver (transceiver) 120 (e.g., for communicating with external devices 110). However, it should be understood that the one or more input devices may include additional types of input devices and / or fewer input devices (e.g., the wireless short-range radio transceiver 120 and / or one or more auxiliary input devices 128 may be omitted).

[0036] The OTE sound processing unit 106 also includes an external coil 108, a charging coil 130, a tightly coupled transmitter / receiver (RF transceiver) 122 (sometimes referred to as a radio frequency (RF) transceiver 122), at least one rechargeable battery 132, and an external sound processing module 124. The external sound processing module 124 may include, for example, one or more processors and a memory device (memory) including sound processing logic. The memory device may include any one or more of the following: non-volatile memory (NVM), ferroelectric random access memory (FRAM), read-only memory (ROM), random access memory (RAM), magnetic disk storage media devices, optical storage media devices, flash memory devices, electrical, optical or other physical / tangible memory storage devices. The one or more processors are, for example, microprocessors or microcontrollers that execute instructions of the sound processing logic stored in the memory device.

[0037] The implantable component 112 includes an implant body (main module) 134, a lead region 136, and an intracochlear stimulation assembly 116, all configured to be implanted beneath the skin / tissue (tissue) 115 of a recipient. The implant body 134 typically includes a hermetically sealed housing 138 in which an RF interface circuit system 140 and a stimulator unit 142 are disposed. The implant body 134 also includes an internal / implantable coil 114, which is typically external to the housing 138 but is accessible via a hermetic feedthrough ( Figure 1D ) is connected to the RF interface circuit system 140.

[0038] As described, the stimulation assembly 116 is configured to be at least partially implanted in the cochlea of ​​a recipient. The stimulation assembly 116 includes a carrier member (e.g., a flexible silicone body) 115 and a plurality of longitudinally spaced intracochlear electrical stimulation contacts (electrodes) 144 disposed in the carrier member. The electrodes 144 collectively form a contact or electrode array 146 for delivering electrical stimulation (electrical current) to the cochlea of ​​the recipient. As shown, the stimulation assembly 116 also includes one or more therapeutic substance delivery portions 162. The therapeutic substance delivery portion(s) 162 contain / include one or more therapeutic substances for delivery to the recipient.

[0039] The stimulation assembly 116 extends through an opening in the recipient's cochlea (e.g., a cochlear fenestration, a round window, etc.) and has a lead region 136 and an airtight feedthrough ( Figure 1D 144 is connected to the proximal end of the stimulator unit 142 (not shown). The lead region 136 includes a plurality of conductors (wires) that electrically couple the electrode 144 to the stimulator unit 142. The implantable component 112 also includes an electrode outside the cochlea, sometimes referred to as an extracochlear electrode (ECE) 139.

[0040] As described, the cochlear implant system 102 includes an external coil 108 and an implantable coil 114. An external magnet 152 is fixed relative to the external coil 108, and the implantable magnet 152 is fixed relative to the implantable coil 114. The magnets fixed relative to the external coil 108 and the implantable coil 114 facilitate operational alignment of the external coil 108 with the implantable coil 114. This operational alignment of the coils enables the external component 104 to transmit data and power to the implantable component 112 via a tightly coupled wireless link 148 formed between the external coil 108 and the implantable coil 114. In some examples, the tightly coupled wireless link 148 is a radio frequency (RF) link. However, various other types of energy transfer (e.g., infrared (IR), electromagnetic, capacitive, and inductive transfer) may be used to transfer power and / or data from the external component to the implantable component, and thus, Figure 1D Only one exemplary arrangement is shown.

[0041] As described above, the sound processing unit 106 includes an external sound processing module 124. The external sound processing module 124 is configured to convert an input signal received (received at one or more of the input devices) into an output signal for stimulating the first ear of the recipient (i.e., the external sound processing module 124 is configured to perform sound processing on the input signal received at the sound processing unit 106). In other words, the one or more processors in the external sound processing module 124 are configured to execute the sound processing logic in the memory to convert the received input signal into an output signal representing electrical stimulation for delivery to the recipient.

[0042] As stated, Figure 1D An embodiment is shown in which an external sound processing module 124 in the sound processing unit 106 generates an output signal. In an alternative embodiment, the sound processing unit 106 can send less processed information (e.g., audio data) to the implantable component 112, and the sound processing operations (e.g., conversion of sound to output signals) can be performed by a processor within the implantable component 112.

[0043] Return to Figure 1D In a specific example of the invention, the output signal is provided to the RF transceiver 122, which transmits the output signal (e.g., in an encoded manner) transcutaneously to the implantable component 112 via the external coil 108 and the implantable coil 114. That is, the output signal is received at the RF interface circuit system 140 via the implantable coil 114 and provided to the stimulator unit 142. The stimulator unit 142 is configured to generate an electrical stimulation signal (e.g., a current signal) for delivery to the cochlea of ​​the recipient using the output signal. In this way, the cochlear implant system 102 electrically stimulates the auditory nerve cells of the recipient, thereby bypassing the missing or defective hair cells that normally convert acoustic vibrations into neural activity in a manner that causes the recipient to perceive one or more components of the received sound signal.

[0044] As described in detail above, in the external listening mode, the cochlear implant 112 receives processed sound signals from the sound processing unit 106. However, in the invisible listening mode, the cochlear implant 112 is configured to capture and process the sound signals for electrical stimulation of the recipient's auditory nerve cells. Figure 1D As shown in , the cochlear implant 112 includes a plurality of implantable sound sensors 160 and an implantable sound processing module 158. Similar to the external sound processing module 124, the implantable sound processing module 158 may include, for example, one or more processors and a memory device (memory) including sound processing logic. The memory device may include any one or more of the following: non-volatile memory (NVM), ferroelectric random access memory (FRAM), read-only memory (ROM), random access memory (RAM), magnetic disk storage media devices, optical storage media devices, flash memory devices, electrical, optical or other physical / tangible memory storage devices. The one or more processors are, for example, microprocessors or microcontrollers that execute instructions of the sound processing logic stored in the memory device.

[0045] In the invisible hearing mode, the implantable sound sensor 160 is configured to detect / capture a signal (e.g., an acoustic sound signal, a vibration, etc.), which is provided to the implantable sound processing module 158. The implantable sound processing module 158 is configured to convert the received input signal (received at one or more implantable sound sensors 160) into an output signal for stimulating the first ear of the recipient (i.e., the processing module 158 is configured to perform a sound processing operation). In other words, the one or more processors in the implantable sound processing module 158 are configured to execute the sound processing logic in the memory to convert the received input signal into an output signal 156 that is provided to the stimulator unit 142. The stimulator unit 142 is configured to generate an electrical stimulation signal (e.g., an electric current signal) for delivery to the cochlea of ​​the recipient using the output signal 156, thereby bypassing the missing or defective hair cells that normally convert the acoustic vibrations into neural activity.

[0046] It should be appreciated that the above description of the so-called external listening mode and the so-called invisible listening mode is merely illustrative, and that cochlear implant system 102 may operate differently in different embodiments. For example, in an alternative embodiment of the external listening mode, cochlear implant 112 may use the signals captured by sound input device 118 and implantable sound sensor 160 to generate stimulation signals for delivery to the recipient.

[0047] As described above, an implantable component, such as cochlear implant 112, may include at least one "therapeutic substance portion" or "drug containing portion (DCP)" that includes one or more therapeutic substances therein for delivery to a recipient. Figure 1D In the example of the present invention, the stimulation component 116 includes two (2) therapeutic substance delivery portions 162. It is to be appreciated that this particular location and number of therapeutic substance delivery portions is merely illustrative, and in the context of the cochlear implant 112, the therapeutic substance portions may be disposed, for example, in the implant body 134, the lead region 136, the stimulation component 116, etc. In addition, and as described in detail below, the therapeutic substance portions according to the embodiments presented herein may have a variety of different arrangements. For example, in some embodiments, the therapeutic substance portion may be a solid material (e.g., silicone) loaded / doped with a therapeutic substance. In other embodiments, the therapeutic substance portion may be a reservoir comprising a solid or liquid therapeutic substance.

[0048] As described above, the technology presented herein measures impedance across a therapeutic substance portion and uses the measured impedance to estimate the state, amount and / or concentration of a therapeutic substance within the therapeutic substance portion. Exemplary techniques for measuring impedance and estimating the state, amount and / or concentration of a therapeutic substance are further described below.

[0049] Figure 2 2 is a schematic diagram illustrating the technology presented herein in the context of an exemplary therapeutic substance portion 262 in the form of a solid material (e.g., silicone loaded with a therapeutic substance). More specifically, Figure 2 2 shows a portion of a stimulation assembly 216 including a carrier member 215 having a plurality of stimulation electrodes 244 disposed therein. The portion of the stimulation assembly 216 shown also includes a therapeutic substance portion 262 disposed in the carrier member 215. In this example, the stimulation electrodes 244 are located at a first side 264 (A) of the carrier member 215, and the therapeutic substance portion 262 is located at a second side 264 (B) of the carrier member 215.

[0050] Figure 2 Also shown are two measuring electrodes, referred to as first measuring electrode 266 (A) and second measuring electrode 266 (B), disposed at first side 268 (A) and second side 268 (B) of therapeutic substance portion 262 (e.g., at opposite ends). Measuring electrodes 266 (A) and 266 (B) are elements of a measuring system (e.g., hardware / circuitry, software, etc.) configured to measure an impedance between the measuring electrodes, the impedance indicating the impedance of / across the therapeutic substance portion 262. As further described below, the measuring system is configured to estimate the state, amount, and / or concentration of the therapeutic substance within therapeutic substance portion 262 based on the measured impedance. As used herein, the term "impedance" refers to electrical impedance (e.g., a measure of relative current flow), and may include the electrical impedance of a material to direct current (DC) and / or alternating current (AC). Impedance may include both resistance and reactance.

[0051] As mentioned, in Figure 2 In the example of , therapeutic substance portion 262 is a solid material filled with a therapeutic substance. The basic concept of the technology described below is that the impedance (conductivity / admittance) of a therapeutic substance portion (such as therapeutic substance portion 262) changes as the therapeutic substance moves (e.g., elutes) into the surrounding fluid. Figure 2 In the example of , the therapeutic substance in the therapeutic substance portion 262 is exposed to an ionic fluid (e.g., physiological fluid / saline, which includes water and proteins / ions). As the therapeutic substance begins to leave the therapeutic substance portion 262, it leaves space that can be filled with the ionic fluid, which has a higher conductivity than the therapeutic substance (e.g., the fluid is more conductive than the therapeutic substance). Therefore, as the therapeutic substance leaves the therapeutic substance portion 262, the impedance of the therapeutic substance portion 262 as measured between the first measurement electrode 266(A) and the second measurement electrode 266(B) will decrease. As described elsewhere herein, the impedance of the therapeutic substance portion 262 is monitored via the first measurement electrode 266(A) and the second measurement electrode 266(B).

[0052] According to the embodiments presented herein, the first measuring electrode 266 (A) and the second measuring electrode 266 (B) are stabilized over time to ensure that any impedance changes are primarily caused by the changing drug state (e.g., amount or concentration) of the therapeutic substance. The stability of the electrodes can be implemented, for example, with a silicon carbide (SiC) coating on platinum (Pt).

[0053] In some embodiments, the interface between the therapeutic substance portion and the electrode(s) 266(A) and / or 266(B) can be prepared to reduce measurement drift and / or other inaccuracies that may be caused by variations in electrical connections. For example, delamination or variations in the contact surface area (e.g., the therapeutic substance portion becomes roughened due to elution) can change the electrical properties of the electrode interface.

[0054] The therapeutic substance portion may be overmolded or adhered to the electrode(s) 266(A) and / or 266(B) in a manner that promotes a stable electrical interface. Areas of the electrode(s) 266(A) and / or 266(B) that are not in contact with the therapeutic substance portion may be coated with a material having a higher impedance than the therapeutic substance portion interface to ensure that most of the current is directed through the therapeutic substance portion.

[0055] In certain embodiments, the system can be configured to accommodate physical and / or electrical changes that may affect measurement accuracy. For example, the measurement processor can be configured to accommodate (e.g., compensate for and / or recalibrate) changes in the electrode interface caused by elution of the drug from the therapeutic substance portion proximate to the electrode (e.g., changes in surface roughness and / or contact surface area).

[0056] Figure 2 An example is shown in which a first measurement electrode 266(A) and a second measurement electrode 266(B) are in physical contact with the therapeutic substance portion 262. It is to be appreciated that in alternative embodiments, one or both of the first measurement electrode 266(A) and the second measurement electrode 266(B) can be spaced apart from the therapeutic substance portion 262 (e.g., in electrical communication such that at least some current or ideally all current passes through the therapeutic substance portion). That is, one or both measurement electrodes are not in direct contact with the therapeutic substance (e.g., a stimulation electrode of an electrode array, or one of the two extracochlear electrodes). The two electrodes need to be in electrical contact, and the therapeutic substance needs to be part of the current path between the two electrodes so that the conductivity change can be measured, and preferably all (or most) of the current passes through the therapeutic substance portion to obtain the strongest signal (impedance change).

[0057] It should also be recognized that the specific positions of the first measurement electrode 266(A) and the second measurement electrode 266(B) are merely illustrative, and each electrode may have other positions closer to the therapeutic substance portion 262.

[0058] In addition, using two electrodes to measure the impedance of the therapeutic substance portion 262 illustrates an exemplary two-terminal (two-point) impedance measurement. Other embodiments presented herein may use different types of impedance measurements, such as three-terminal (three-point) impedance measurement, four-terminal (four-point) impedance measurement, etc. The three-terminal measurement uses a first electrode and a second electrode (current-carrying electrodes) to conduct current, and a third non-current-carrying electrode (the so-called "reference electrode") placed between the first electrode and the second electrode. In this arrangement, the impedance change between the first electrode and the third electrode is measured. In the four-terminal arrangement, there are a first current-carrying electrode and a second current-carrying electrode, and a third voltage-sensing reference electrode and a fourth voltage-sensing reference electrode placed between the current-carrying electrodes. In this arrangement, the impedance between the two reference electrodes is measured. Using a reference electrode can have the benefit of limiting the influence of changes at the electrode-electrolyte interface (electrode surface) on the measured impedance. This can help ensure that the impedance change is dominated by the change in the "bulk" (here, the volume of the therapeutic substance) between the electrodes rather than between complex electrode interfaces. Therefore, using two electrodes for impedance measurement is merely illustrative, and other embodiments may use additional electrodes.

[0059] Moreover, Figure 2 A specific arrangement with two dedicated measurement electrodes is shown. Using two measurement electrodes is merely illustrative, and other arrangements may use, for example, one or more stimulation electrodes 244 to perform impedance measurement. For example, in one such arrangement, current is delivered via the measurement electrode 266(A) and returns via one of the stimulation electrodes 244. In this arrangement, the measurement electrode 266(A) may be omitted (or used in, for example, a three-terminal or four-terminal measurement).

[0060] Figures 3A-3D is a series of schematic diagrams showing the impedance change across the therapeutic substance portion 262. More specifically, Figure 3A shows the impedance Z1 of the therapeutic substance portion 262 in the dry state (e.g., before implantation), while Figure 3B shows the impedance Z2 of the therapeutic substance portion 262 in the initial wet state (e.g., immediately after implantation). As shown, the impedance of the therapeutic substance portion 262 is very high (Z1) in the dry state, but this impedance decreases in the initial wet state (Z2 < Z1). That is, in the dry state ( Figure 3A ), there is a high impedance (Z1) across the therapeutic substance portion 262. The reason for the absence of current flow in the dry state (e.g., for silicone with drug molecules, no ion movement). In the initial wet state ( Figure 3B ), there is a lower impedance (Z2) across the therapeutic substance portion 262.

[0061] Figure 3C and 3D Two time points after implantation are shown, i.e. at which some of the therapeutic substance has eluted ( Figure 3C ) and the therapeutic substance portion 262 at a point where a small amount of therapeutic substance remains in the therapeutic substance portion 262. As shown, as more and more therapeutic substance leaves the therapeutic substance portion 262 and is replaced by the ionic fluid, the impedance Z3, Z4 of the therapeutic substance portion 262 continues to decrease (Z2>Z3>Z4). That is, when the therapeutic substance begins to leave the therapeutic substance portion 262 ( Figure 3C ), the therapeutic substance will leave space, and the space can be filled with an ionic fluid (e.g., a physiological fluid such as saline) having a higher conductivity than the therapeutic substance. Therefore, when the therapeutic substance leaves the therapeutic substance portion 262 (e.g., elutes into the perilymph), the impedance across the therapeutic substance should decrease.

[0062] In short, Figure 2 and 3A In the example of -3D, from very high impedance (Z1) to reduced impedance (Z2), but as more therapeutic substance leaves, the impedance will become lower (Z3) and lower and lower (Z4) because the ionic fluid (saline) is more conductive than the therapeutic substance. The more space left in the therapeutic substance portion 262, the lower the impedance will become as the space is filled with higher conductivity ionic fluid (saline) as the lower conductivity therapeutic substance elutes. Therefore, in the case of uncoated therapeutic substance portion 262, the impedance can be reduced over time.

[0063] Figure 4 4 is a schematic diagram illustrating the technology presented herein in the context of an exemplary therapeutic substance portion 462 in the form of a solid material (e.g., silicone loaded with a therapeutic substance). More specifically, Figure 4 A portion of the stimulation assembly 416 is shown in FIG. 4 , wherein a portion of the stimulation assembly includes a plurality of stimulation electrodes ( Figure 4 The portion of the stimulation component 416 shown also includes a therapeutic substance portion 462 disposed in the carrier member 415.

[0064] Figure 4Also shown are two measurement electrodes, referred to as first measurement electrode 466(A) and second measurement electrode 466(B), disposed at first side 468(A) and second side 468(B) (e.g., at opposite ends) of therapeutic substance portion 462, respectively. Measurement electrodes 466(A) and 466(B) are connected to a measurement system (e.g., hardware / circuitry, software, etc.) configured to measure an impedance between the measurement electrodes, the impedance indicating the impedance of / across the therapeutic substance portion 462. As further described below, the measurement system is configured to estimate the state, amount, and / or concentration of the therapeutic substance within therapeutic substance portion 462 based on the measured impedance.

[0065] As stated, Figure 4 The use of two measuring electrodes 466 (A) and 466 (B) is shown. In some embodiments, at least one of the two measuring electrodes can be replaced by a stimulation electrode (such as an intracochlear electrode). In one such embodiment, the stimulation electrode is used for neural stimulation and is used as a return electrode for measuring the impedance of the therapeutic substance portion 462.

[0066] As mentioned, in Figure 4 In the example of , therapeutic substance portion 462 is a solid material containing a therapeutic substance. The basic concept of the technology described below is that the conductivity (admittance / impedance) of a therapeutic substance portion (such as therapeutic substance portion 462) changes as the therapeutic substance moves (e.g., elutes) into the surrounding fluid. However, in Figure 4 In the example shown, the therapeutic substance portion 462 is covered by a silicone (eg, PDMS) layer 472. With silicone coating the therapeutic substance portion 462, the impedance may initially decrease but then increase over time.

[0067] More specifically, in Figure 4 In the example of FIG. 4 , the space / pore / opening created by the therapeutic substance leaving the therapeutic substance portion 462 is filled with pure water (H2O) because the ionic fluid (saline) cannot pass through the silicone layer 472 covering the therapeutic substance portion 462. Pure water is a poor conductor (compared to ionic fluid / saline). The silicone layer 472 is an ion barrier and will not allow salt ions (i.e., sodium (Na + ) and chlorine (Cl - ) ions) will pass through, but will allow pure water (H2O) to pass through, while the therapeutic substance will elute out.

[0068] Figure 5 It is generally shown Figure 4, namely, a graph showing how impedance changing over time can indicate the state, amount, and / or concentration of a therapeutic substance in a therapeutic substance portion. In this example, water molecules enter the therapeutic substance portion 462 and dissolve a solid therapeutic substance (e.g., dexamethasone (Dex)), and the solid therapeutic substance is replaced by a saturated therapeutic solution (e.g., water plus therapeutic substance). Thereafter, the saturated substance is released through the silicone layer 472, and more pure water molecules move in, dissolving more solid therapeutic substance. Over time, the volume of the solid therapeutic substance decreases, and the volume of the space filled with the saturated therapeutic solution increases. According to the method, the impedance decreases over time due to the increase in the volume of the saturated therapeutic solution in the porous bulk silicone body. The impedance is lowest when all of the solid therapeutic substance is replaced by the saturated therapeutic solution. As the remaining therapeutic solution is released, the impedance begins to rise again. Once all of the therapeutic solution disappears and the pores are filled with pure water, the impedance reaches a second peak.

[0069] Therefore, as described above and further described below, some exemplary embodiments of the present disclosure involve measuring the amount of therapeutic substance that has not eluted, so as to thereby determine the amount of therapeutic substance that has eluted into the cochlea (e.g., the amount of therapeutic substance eluted = the total amount of therapeutic substance - the amount of therapeutic substance that has not eluted). This may involve measuring the amount of therapeutic substance retained in the therapeutic substance portion, so as to thereby determine the amount of therapeutic substance that has eluted. Some exemplary embodiments involve estimating the state of the therapeutic substance portion from the characteristics and / or trends of the measured impedance. For example, the processor may be configured to estimate the state of the therapeutic substance portion from the rate of change of the measured impedance. In some embodiments, the processor may be configured to determine that the therapeutic substance portion is substantially exhausted when the measured impedance reaches a steady state (e.g., the rate of change of the measured impedance drops below a threshold).

[0070] Figure 6 662 is a schematic diagram illustrating the technology presented herein in the context of an exemplary therapeutic substance portion 662 in the form of a reservoir (e.g., containing a therapeutic substance in liquid or solid form). More specifically, Figure 6 6, and includes a carrier member 615 in which a plurality of stimulation electrodes 644 are disposed. The portion of the stimulation member 616 shown also includes a therapeutic substance portion 662 disposed in the carrier member 615.

[0071] Figure 6Also shown are two measuring electrodes disposed at a first side 668(A) and a second side 668(B) of the therapeutic substance portion 662 (e.g., at opposite sides), referred to as a first measuring electrode 666(A) and a second measuring electrode 666(B). The measuring electrodes 666(A) and 666(B) are connected to a measuring system (e.g., hardware / circuitry, software, etc.), which is configured to measure an impedance between the measuring electrodes, the impedance indicating the impedance of / across the therapeutic substance portion 662. As further described below, the measuring system is configured to estimate a state, amount, and / or concentration of a therapeutic substance within the therapeutic substance portion 662 based on the measured impedance. Optionally, as Figure 6 As shown in the dashed lines, another pair of measuring electrodes 666 (C) and 666 (D) may be disposed at the first side and the second side of the therapeutic substance portion 662, respectively. Figure 6 The dashed lines in the diagram showing the measurement electrodes 666 (C) and 666 (D) actually indicate that the first measurement electrode 666 (A) and the second measurement electrode 666 (B) can have different placement positions along the therapeutic substance portion 662. Exemplary embodiments are not limited to the number of measurement electrode pairs and / or the positions of the measurement electrodes along both sides of the therapeutic substance portion 662.

[0072] exist Figure 6 In the example of FIG. 6 , the therapeutic substance portion 662 is a liquid reservoir and is a diffusion system. In a diffusion system, the fluid does not physically move, but the concentration of the therapeutic substance changes over time. That is, there is a concentration gradient for the therapeutic substance molecules to move toward an area of ​​lesser concentration (one end of the reservoir 662 in the illustrated embodiment). The sensor (e.g., Figure 6 The measuring electrodes 666A / 666B and / or 666C / 666D and / or 666A / 666C and / or 666B / 666D) can measure the impedance at any given point from the reservoir to the delivery site. In certain embodiments, the measurement system can measure the impedance at two points across the length to measure the difference. Figure 6 In the example of , the concentration of the therapeutic substance is changing, which can be measured via changing impedance as described elsewhere herein.

[0073] As described above, aspects of the technology presented herein use an impedance measurement system to capture / record impedance measurements. Figure 7 7 is a functional block diagram illustrating an exemplary impedance measurement system 771 configured to implement aspects of the techniques presented herein. Impedance measurement system 771 may be implemented, for example, in part or in whole by an implantable medical device (e.g., cochlear implant 102), a combination of an implantable medical device and an external device (e.g., cochlear implant 102 and external device 110), multiple implantable medical devices, multiple implantable medical devices and multiple external devices, etc.

[0074] like Figure 7 As shown in , the impedance measurement system 771 includes a control module 773, at least two measurement electrodes (referred to as measurement electrodes 766(A) and 766(B)), a recording module 774, an analysis module 776, and in some arrangements a temperature sensor 775. The analysis module 776, the recording module 774, and the control module 773 may be implemented in hardware, software, and / or a combination thereof.

[0075] exist Figure 7 In a specific illustrative example of the present invention, the recording module 774 is configured to capture / record multiple impedances across the therapeutic substance portion. In some examples, the control module 773 instructs the recording module 774 to perform one or more impedance measurements. The recording module 774 can be configured to amplify the measured impedances and provide the measured impedances to the analysis module 776, among other operations.

[0076] The analysis module 776 is configured to use the measured impedance to estimate the state, amount and / or concentration of the therapeutic substance in the therapeutic substance portion of the subject. In addition, the analysis module 776 can generate one or more outputs 778 representing the state, amount and / or concentration. In some embodiments, the one or more outputs 778 can be audible or visual outputs. In other embodiments, as further described below, the one or more outputs 778 can be control outputs that are sent to, for example, the control module 773 to be used as part of a closed-loop control system.

[0077] These exemplary embodiments provide several advantages, including knowing when the therapeutic substance portion is substantially depleted in order to monitor physiological / electrophysiological changes, knowing when to replace the therapeutic substance portion, when to refill the therapeutic substance portion, and / or confirming that the replacement / replenishment of the therapeutic substance was successful (through a confirmatory change in conductivity). In general, the therapeutic substance state, amount, and / or concentration information can be utilized in many ways to allow the surgeon to optimize or modify the recipient's treatment plan. For example, for a therapeutic substance with a toxicity limit, the physician can use the therapeutic substance state, amount, and / or concentration to determine whether additional systemic administration (if a condition occurs in the ear) is feasible while the drug is still being eluted (e.g., if the toxicity limit has been exhausted, the physician can prescribe oral steroids, etc.). With respect to the refillable therapeutic substance portion, the therapeutic substance state, amount, and / or concentration can be used to monitor, for example, delivery rate, prescribe / information, understand the impact on other electrophysiological metrics (e.g., if 4P impedance begins to rise, it may indicate different conditions when the therapeutic substance is present versus when the therapeutic substance is absent), etc.

[0078] In some embodiments, the measured impedance / conductivity may be temperature dependent (i.e., the impedance may vary significantly with temperature). Thus, a temperature sensor 775 may also be provided proximate to the therapeutic substance portion. Figure 7 ), and the temperature recorded by the temperature sensor 775 can be used to compensate the impedance measurement to account for the varying temperature. The temperature sensor can be, for example, a resistance wire. In embodiments where the temperature of the tissue surrounding the therapeutic substance portion is expected to vary (e.g., a subcutaneous device), the measured impedance may not be accurate if the temperature is not controlled. Therefore, the temperature measurement can be used to calibrate / compensate / correct the impedance measurement across the therapeutic substance portion (e.g., to analyze conductivity). The temperature sensor can also be used for other purposes, such as temperature monitoring, local inflammation temperature monitoring, etc.

[0079] In connection with the various exemplary embodiments described above with reference to Figure 8 , 9 , 10 and 11 describe various methods below.

[0080] Figure 8 An exemplary method 800 for monitoring the state, amount, and / or concentration of a therapeutic substance in a therapeutic substance portion using a measurement system according to aspects of the present disclosure is shown. Specifically, the measurement system measures impedance across the therapeutic substance portion (step 810), and estimates the state, amount, and / or concentration of the therapeutic substance remaining within the therapeutic substance portion based on the measured impedance (step 820).

[0081] Fig. 9 An exemplary method 900 for monitoring the state, amount, and / or concentration of a therapeutic substance in a therapeutic substance portion using a measurement system according to another aspect of the present disclosure is shown. In this variation, a measurement electrode associated with the therapeutic substance portion is used to measure a first impedance across the therapeutic substance portion at a first time (T1) (step 910). The measurement electrode associated with the therapeutic substance portion is then used to measure a second impedance across the therapeutic substance portion at a second time (T2) (step 920). Based on the change between the first measured impedance at time T1 and the second measured impedance at time T2, the state, amount, and / or concentration of the therapeutic substance remaining in the therapeutic substance portion is estimated (step 930). In this variation, in order to estimate the state, amount, and / or concentration of the remaining therapeutic substance, the first impedance value and the second impedance value can be compared, and the difference between the pair of values ​​(along with the direction of change, increase versus decrease) can be determined. The rate of change and / or the amount of change can indicate the concentration of the therapeutic substance remaining in the therapeutic substance portion after a certain period of time.

[0082] Fig.10An exemplary method 1000 for monitoring the state, amount, and / or concentration of a therapeutic substance in a therapeutic substance portion using an impedance measurement system (e.g., hardware / circuitry, software, etc.) and a temperature sensor according to aspects of the present disclosure is shown. Specifically, the measurement system measures impedance across the therapeutic substance portion (step 1010), and estimates the state, amount, and / or concentration of the therapeutic substance remaining within the therapeutic substance portion based on the measured impedance (step 1020).

[0083] In this variation, method 1000 also includes detecting a temperature proximate the therapeutic substance portion using a temperature sensor (step 1030), and calibrating / compensating / correcting an estimated state, amount and / or concentration of the therapeutic substance remaining within the therapeutic substance portion based on the measured temperature (step 1040).

[0084] Fig.11 Another exemplary method 1100 for monitoring the state, amount, and / or concentration of a therapeutic substance in a therapeutic substance portion using an impedance measurement system (e.g., hardware / circuitry, software, etc.) and a temperature sensor according to another aspect of the present disclosure is shown. Specifically, the measurement system measures impedance across the therapeutic substance portion (step 1110), and in this variation, a temperature sensor is used to detect a temperature near the therapeutic substance portion (step 1120). The measurement system then estimates the state, amount, and / or concentration of the therapeutic substance remaining within the therapeutic substance portion based on the measured impedance and the detected temperature (step 1130).

[0085] In methods 1000 and 1100 above, various adjustments may be made to increase or decrease the measured impedance to account for temperature in order to make therapeutic substance state, amount and / or concentration estimates more accurate (since impedance may generally vary at higher and lower temperatures).

[0086] Some other exemplary embodiments will now be described with additional explanatory details. One exemplary embodiment uses a water-soluble molecular coating (which may be a therapeutic substance or just an indicator) only on electrodes, in a reservoir, or on electrodes on the outer surface of an electrode array. The outer surface electrodes are used to determine the state, amount, and / or concentration of the therapeutic substance in the cochlea, which in turn can be used to infer the amount of therapeutic substance delivered. When the concentration in the cochlea (or reservoir) reaches a certain target level, the molecules leave the layer disposed on the electrode. For example, an electrode close to the therapeutic substance delivery point can be used because this will ensure a high concentration close to the layer (at the beginning). Measurements can be made, for example, between an intra-cochlear electrode and an extra-cochlear electrode. The therapeutic substance or other water-soluble molecules can be separate or loaded into a polymer matrix. In addition, the matrix can include different water-soluble molecules with different outlets. For example, molecules that are not released until the therapeutic substance in the reservoir is 10% (or some other threshold) can be used.

[0087] Another exemplary embodiment uses a coating containing a therapeutic substance (e.g., a dexamethasone eluting silicone coating) on ​​one or both electrodes inside a reservoir filled with a therapeutic substance solution. As long as the concentration of the solution is at the solubility limit at a given temperature (e.g., 37 degrees), the therapeutic substance in the coating will remain solid. In this state, the impedance between the two electrodes is stable over time. When the therapeutic substance is released from the reservoir, the concentration of the solution drops below the solubility limit, and some amount of solid therapeutic substance from the coating will enter the solution to compensate the solution (e.g., keep the solution close to the solubility limit concentration). This will reduce the impedance between the two electrodes. In this case, the impedance change is a measure of how much therapeutic substance the reservoir has released into the body. The solid therapeutic substance acts as the reservoir itself. When all the solid therapeutic substances in the coating are dissolved, no significant impedance change will be measured, but the solution in the reservoir is still at the same concentration (solubility limit). In this final stage, the therapeutic substance will continue to be released into the body, and the impedance will no longer change significantly until all the therapeutic substances have left the device. This extends the concept to the (indirect) measurement of the concentration of the liquid therapeutic substance.

[0088] As previously mentioned, the technology disclosed herein can be applied to any of a variety of situations and used with a variety of different devices. Fig.12 and 13 Exemplary devices that may benefit from the techniques disclosed herein are described in more detail in .

[0089] Fig.12 An exemplary vestibular stimulator system 1202 is shown, which can be used to implement the embodiments presented herein. As shown, the vestibular stimulator system 1202 includes an implantable component (vestibular stimulator) 1212 and an external device / component 1204 (e.g., an external processing device, a battery charger, a remote control, etc.). The external device 1204 includes a transceiver unit 1260. Thus, the external device 1204 is configured to transmit data (and possibly power) to the vestibular stimulator 1212.

[0090] The vestibular stimulator 1212 includes an implant body (main module) 1234, a lead region 1236, and a stimulation assembly 1216, all configured to be implanted beneath the skin / tissue (tissue) of a recipient. The implant body 1234 generally includes an airtight sealed housing 1238 in which an RF interface circuit system, one or more rechargeable batteries, one or more processors, and a stimulator unit are disposed. The implant body 1234 also includes an internal / implantable coil 1214, which is generally external to the housing 1238 but connected to a transceiver via an airtight feedthrough (not shown).

[0091] The stimulation assembly 1216 includes a plurality of electrodes 1244(1)-(3) disposed in a carrier member (e.g., a flexible silicone body). In this particular example, the stimulation assembly 1216 includes three (3) stimulation electrodes, referred to as stimulation electrodes 1244(1), 1244(2), and 1244(3). The stimulation electrodes 1244(1), 1244(2), and 1244(3) serve as an electrical interface for delivering electrical stimulation signals to the vestibular system of a recipient.

[0092] The stimulation assembly 1216 is configured so that a surgeon can implant the stimulation assembly near the recipient's otolith organ via, for example, the recipient's oval window. It should be understood that this particular embodiment with three stimulation electrodes is merely illustrative, and the techniques presented herein can be used with stimulation assemblies with different numbers of stimulation electrodes, stimulation assemblies with different lengths, etc.

[0093] As shown, the implant body 1234 also includes one or more therapeutic substance delivery portions 1262. The therapeutic substance delivery portion(s) 1262 contain / include one or more therapeutic substances for delivery to a recipient. The implant body 1234 also includes a measurement system ( Fig.12 ), as described elsewhere herein, the measurement system is configured to measure impedance across one or more therapeutic substance delivery portions 1262, and use the impedance to determine the state, amount and / or concentration of (one or more) therapeutic substances in the one or more therapeutic substance delivery portions 1262.

[0094] Fig.13 A retinal prosthesis system 1301 is shown that includes an external device 1310 configured to communicate with a retinal prosthesis 1300 via a signal 1351. The retinal prosthesis 1300 includes an implantable processing module 1325, and a retinal prosthesis sensor-stimulator 1390 is positioned proximate to the recipient's retina. The external device 1310 and the processing module 1325 can communicate via coils 1308, 1314.

[0095] In an example, sensory input (e.g., photons entering the eye) is absorbed by a microelectronic array of a sensor-stimulator 1390 that is hybridized with a glass piece 1392 that includes, for example, an embedded microwire array. The glass may have a curved surface that conforms to the inner radius of the retina. The sensor-stimulator 1390 may include a microelectronic imaging device that may be made of thin silicon containing an integrated circuit system that converts incident photons into electronic charges.

[0096] The processing module 1325 includes an image processor 1323, which is in signal communication with the sensor-stimulator 1390 via, for example, a lead 1388 extending through a surgical incision 1389 formed in the eye wall. In other examples, the processing module 1325 is in wireless communication with the sensor-stimulator 1390. The image processor 1323 processes the input of the sensor-stimulator 1390 and provides control signals back to the sensor-stimulator 1390 so that the device can provide an output to the optic nerve. That is, in an alternative example, the processing is performed by a component close to or integrated with the sensor-stimulator 1390. The charge generated by the conversion of the incident photons is converted into a proportional amount of electronic current, which is input to the nearby retinal cell layer. The cells are excited, and signals are sent to the optic nerve, thereby inducing visual perception.

[0097] The processing module 1325 may be implanted in the recipient and function by communicating with an external device 1310, such as a behind-the-ear unit, a pair of glasses, etc. The external device 1310 may include an external light / image capture device (e.g., located in / on the behind-the-ear unit or a pair of glasses, etc.), while, as described above, in some examples, the light / image is captured by a sensor-stimulator 1390, which is implanted in the recipient.

[0098] As shown, one or more therapeutic substance delivery portions 1362 can be implanted in the recipient. The therapeutic substance delivery portion(s) 1362 contain / include one or more therapeutic substances for delivery to the recipient. The retinal prosthesis system 1301 also includes a measurement system ( Fig.13 ), as described elsewhere herein, the measurement system is configured to measure impedance across one or more therapeutic substance delivery portions 1362, and use the impedance to determine the state, amount and / or concentration of (one or more) therapeutic substances in the one or more therapeutic substance delivery portions 1362.

[0099] It should be understood that although specific uses of the present technology have been illustrated and discussed above, the disclosed technology can be used with various devices according to many examples of the present technology. The above discussion is not intended to indicate that the disclosed technology is only suitable for implementation in systems similar to those shown in the accompanying drawings. In general, additional configurations can be used to practice the processes and systems herein, and / or some aspects described can be excluded without departing from the processes and systems disclosed herein.

[0100] The present disclosure describes some aspects of the present invention technology with reference to the accompanying drawings, in which only some possible aspects are shown. However, other aspects may be embodied in many different forms and should not be construed as being limited to the aspects set forth herein. Instead, these aspects are provided to make the present disclosure detailed and complete and to fully convey the scope of possible aspects to those skilled in the art.

[0101] It should be understood that the various aspects (e.g., parts, components, etc.) described herein with respect to the figures are not intended to limit the systems and processes to the specific aspects described. Therefore, additional configurations can be used to practice the methods and systems herein, and / or some aspects described can be excluded without departing from the methods and systems disclosed herein.

[0102] According to certain aspects, a system and a non-transitory computer-readable storage medium are provided. The system is configured with hardware configured to perform operations similar to the method of the present disclosure. One or more non-transitory computer-readable storage media include instructions that, when executed by one or more processors, cause the one or more processors to perform operations similar to the method of the present disclosure.

[0103] Similarly, where steps of a process are disclosed, these steps are described for the purpose of illustrating the present methods and systems, and are not intended to limit the present disclosure to a particular sequence of steps. For example, the steps may be performed in a different order, two or more steps may be performed simultaneously, additional steps may be performed, and disclosed steps may be eliminated without departing from the present disclosure. Furthermore, the disclosed processes may be repeated.

[0104] Although specific aspects are described herein, the scope of the present technology is not limited to these specific aspects. Those skilled in the art will recognize other aspects or improvements within the scope of the present technology. Therefore, specific structures, actions or media are disclosed only as illustrative aspects. The scope of the present technology is limited by the attached claims and any equivalents therein.

[0105] It should also be understood that the embodiments presented herein are not mutually exclusive and that various embodiments can be combined with another embodiment in any of a variety of different ways.

Claims

1. A system comprising: at least one therapeutic substance portion comprising a therapeutic substance; as well as A measurement system is configured to measure impedance across the at least one therapeutic substance portion and to estimate a state of the therapeutic substance within the at least one therapeutic substance portion based on the measured impedance across the at least one therapeutic substance portion.

2. The system of claim 1, wherein the measurement system comprises at least a first electrode and a second electrode disposed at opposite sides of the at least one therapeutic substance portion.

3. The system of claim 2, wherein the first electrode is in physical contact with the at least one therapeutic substance portion and the second electrode is physically separated from the at least one therapeutic substance portion.

4. The system of claim 2, wherein the second electrode is an electrode configured to deliver an electrical stimulation signal to tissue of a recipient.

5. The system of claim 2, wherein the first electrode and the second electrode are each in physical contact with the at least one therapeutic substance portion.

6. The system of claim 2, wherein the at least one therapeutic substance portion comprises silicone encapsulated with the therapeutic substance.

7. The system of claim 2, wherein the first electrode and the second electrode are configured to be stable over time.

8. The system of claim 1, wherein the measurement system comprises a first pair of opposing electrodes disposed across a first segment of the at least one therapeutic substance portion and a second pair of opposing electrodes disposed across a second segment of the at least one therapeutic substance portion.

9. The system of claim 1, 2, 3, 4, 5, 6, 7 or 8, further comprising a temperature sensor configured to detect a temperature proximate to the at least one therapeutic substance portion.

10. The system of claim 1, wherein the measurement system is configured to estimate a concentration of the therapeutic substance within the at least one therapeutic substance portion.

11. The system of claim 9, wherein the measurement system is configured to estimate a concentration of the therapeutic substance within the at least one therapeutic substance portion based on the measured impedance across the at least one therapeutic substance portion and the temperature near the at least one therapeutic substance portion detected by the temperature sensor.

12. The system of claim 1, 2, 3, 4, 5, 6, 7 or 8, wherein the at least one therapeutic substance portion is disposed within and substantially surrounded by a polymer body and includes at least one exposed surface.

13. The system of claim 1, 2, 3, 4, 5, 6, 7 or 8, wherein the at least one therapeutic substance is partially disposed in and substantially surrounded by a polymer body and comprises a first surface, and wherein the polymer layer is disposed on the first surface.

14. The system of claim 13, wherein the polymer layer comprises one or more openings.

15. The system of claim 1, 2, 3, 4, 5, 6, 7 or 8, wherein the at least one therapeutic substance portion is a solid polymer loaded with at least one therapeutic substance.

16. The system of claim 1, 2, 3, 4, 5, 6, 7 or 8, wherein the at least one therapeutic substance portion is a reservoir containing at least one fluid therapeutic substance.

17. The system of claim 1, 2, 3, 4, 5, 6, 7 or 8, wherein the system is an implantable medical device system.

18. The system of claim 17, wherein the implantable medical device system is a cochlear implant.

19. A method comprising: measuring impedance of at least one therapeutic substance portion comprising a therapeutic substance; as well as A state of the therapeutic substance within the at least one therapeutic substance portion is estimated based on the measured impedance.

20. The method of claim 19, wherein measuring the impedance of the at least one therapeutic substance portion comprises: At least one two-terminal impedance measurement is performed using a first electrode and a second electrode separated by the at least one therapeutic substance portion.

21. The method of claim 19, wherein measuring the impedance of the at least one therapeutic substance portion comprises: At least one three-terminal impedance measurement is performed using a first electrode, a second electrode, and a third electrode disposed around the at least one therapeutic substance portion.

22. The method of claim 19, wherein measuring the impedance of the at least one therapeutic substance portion comprises: At least one four-terminal impedance measurement is performed using a first electrode, a second electrode, a third electrode, and a fourth electrode disposed around the at least one therapeutic substance portion.

23. The method of claim 19, wherein measuring the impedance of the at least one therapeutic substance portion comprises: measuring a first impedance at a first time; as well as measuring a second impedance at a second time, Wherein the state of the therapeutic substance within the at least one therapeutic substance portion is estimated using the first impedance and the second impedance.

24. The method according to claim 23, further comprising: A difference between the first impedance and the second impedance is determined.

25. The method of claim 19, wherein measuring the impedance of the at least one therapeutic substance portion comprises: measuring a first impedance at a first region of at least one therapeutic substance portion; as well as measuring a second impedance at a second region of the at least one therapeutic substance portion, Wherein the state of the therapeutic substance within the at least one therapeutic substance portion is estimated using the first impedance and the second impedance.

26. The method of claim 19, further comprising: detecting a temperature proximate to the at least one therapeutic substance portion using a temperature sensor; as well as The state of the therapeutic substance within the at least one therapeutic substance portion is estimated based on the measured impedance and the detected temperature.

27. The method of claim 19, 20, 21, 22, 23, 24, 25 or 26, wherein the at least one therapeutic substance portion comprises silicone encapsulated with the therapeutic substance.

28. The method of claim 19, 20, 21, 22, 23, 24, 25 or 26, wherein the at least one therapeutic substance portion is disposed within and substantially surrounded by a polymer body and includes at least one exposed surface.

29. The method of claim 19, 20, 21, 22, 23, 24, 25 or 26, wherein the at least one therapeutic substance is partially disposed in and substantially surrounded by a polymer body and comprises a first surface, and wherein the polymer layer is disposed on the first surface.

30. The method of claim 19, 20, 21, 22, 23, 24, 25 or 26, wherein the at least one therapeutic substance portion is a solid polymer loaded with at least one therapeutic substance.

31. The method of claim 19, 20, 21, 22, 23, 24, 25 or 26, wherein the at least one therapeutic substance portion is a reservoir containing at least one fluid therapeutic substance.

32. One or more non-transitory computer-readable storage media comprising instructions that, when executed by a processor, cause the processor to: obtaining an impedance of at least one therapeutic substance portion; and An amount of at least one therapeutic substance remaining within the at least one therapeutic substance portion is estimated based on the impedance of the at least one therapeutic substance portion.

33. The one or more non-transitory computer-readable storage media of claim 32, wherein the instructions that when executed cause the processor to obtain the impedance of at least one therapeutic substance portion include instructions that cause the processor to: The impedance of at least one therapeutic substance portion is measured using at least a first electrode and at least a second electrode positioned proximate to the at least one therapeutic substance portion.

34. The one or more non-transitory computer-readable storage media of claim 32, wherein the instructions that when executed cause the processor to obtain the impedance of at least one therapeutic substance portion comprise instructions that cause the processor to: The impedance of at least one therapeutic substance portion is measured using at least a first electrode, at least a second electrode, and at least a third electrode positioned proximate to the at least one therapeutic substance portion.

35. The one or more non-transitory computer-readable storage media of claim 32, wherein the instructions that when executed cause the processor to obtain the impedance of at least one therapeutic substance portion include instructions that cause the processor to: The impedance of at least one therapeutic substance portion is measured using at least a first electrode, at least a second electrode, at least a third electrode, and at least a fourth electrode positioned proximate to the at least one therapeutic substance portion.

36. The one or more non-transitory computer-readable storage media of claim 32, 33, 34, or 35, further comprising instructions executable to: obtaining a temperature measured in the vicinity of the at least one therapeutic substance portion; and The amount of at least one therapeutic substance remaining within the at least one therapeutic substance portion is estimated further based on the temperature.

37. A system comprising: at least one therapeutic substance portion comprising a therapeutic substance, the at least one therapeutic substance portion being configured to be implantable into a body of a recipient; at least a first electrode and at least a second electrode, the at least first electrode and the at least second electrode configured to be implanted in the recipient proximate the therapeutic substance; circuitry configured to measure impedance between the at least first electrode and the at least second electrode; as well as At least one processor is configured to estimate a concentration of the therapeutic substance in the therapeutic substance portion from the measured impedance.

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