A full-custom fully implantable cochlear implant system validated in vivo with an animal model – Communications Engineering

Design and realization of full-custom FICI system

The full-custom FICI system designed to sense daily sound signals and stimulate auditory neurons according to sound levels and frequencies is presented in Fig. 1a28,29. Sound vibrations are converted to mechanical vibrations on the eardrum and sensed by a low-profile acoustic sensor comprised of multi-channel PZT sensors acting as mechanical filters. The outputs of these sensors were evaluated by low-power signal-conditioning interface electronics, which generated stimulation pulses for auditory neurons. The neural stimulation pulses were delivered to auditory neurons through an intra-cochlear electrode. The interface electronics was powered by a rechargeable battery, chargeable through a radio frequency (RF) coil also used for post-implantation patient fitting applications.

Fig. 1: Full-custom fully implantable cochlear implant system architecture and sub-components.
figure 1

a Detailed representation of the full-custom fully implantable cochlear implant (FICI) system where the piezoelectric sensor is located on the eardrum, the sensor outputs are provided to the signal conditioning circuit with flexible interconnects, then the generated electrical stimulation pulses at signal conditioning circuit are delivered to the cochlea with intra-cochlear electrodes. The power and patient fitting controls of the signal conditioning circuit can be delivered through a rechargeable battery and a radio frequency coil. b 3D illustration of the bilayer sound sensor including spacers, caps and flexible interconnect connections. c Fabricated sound sensor with an overall size of 3.5 × 3.5 mm2. d Micrograph of the fabricated signal conditioning circuit with highlighted sub-blocks where LA stands for logarithmic amplifiers, CR is current rectifiers, LPF is low-pass filters, S/H is sample and Hold, Ctrl is control unit, V/I is voltage to current converter and SM is switch matrix circuits. e Schematic representation of the signal conditioning interface electronics.

Key considerations for sound sensing and processing in the middle ear include: (1) The compact structure of the sound sensor due to restrictive volume and area in the middle ear and intricacies of middle ear surgery; (2) placement of the sound sensor directly on the ossicular chain without anchoring to the middle ear walls to avoid reducing the middle ear’s vibration level through mass and force loadings; (3) the crucial role of the number of frequency bands in maintaining natural sound characteristics, despite the increased processing power required; (4) human voice mainly includes frequencies between 250 and 4000 Hz, with lower frequencies encompassing body noise and higher frequencies necessary for speech perception in noisy environments, hence the resonance frequencies of the frequency bands should be appropriately placed; and (5) the need for custom-designed ultra-low-power interface circuits to efficiently stimulate auditory neurons, with a novel PZT sensor designed for a wide dynamic range and maintaining a high signal-to-noise ratio at the output.

Commonly used PZT sensors for this application are beam structures with piezoelectric films in the 31-mode, which can produce high strain depending on the deflection of the beam. Using tipmass increases deflection and strain on the piezoelectric film, thus improving output voltage. Additionally, these masses allow for denser structures by reducing the beam lengths, enabling sound detection from vibration of hearing chain while resonating in the hearing frequency range. Center frequencies of the bands are matched with resonance frequencies of the beams. Researches in the literatures indicate that 8-channel systems are ideal for low-power applications, with frequencies spread linearly from 300 to 1200 Hz and distributed logarithmically above 1200 Hz. in daily sound signals30. Thin-film PLD-PZT (MESA+ Institute, Netherland), was seleceted for its superior PZT properties, allowing for a wide dynamic range.

The volume and area constraints of the implantable system were managed with a bilayer transducer design. Channels were located with respect to their length to optimize the dimension of the structure. The layer consisting three channels, includes beams resonating at 300, 1200, and 1600 Hz. Thelayer consisting five channels has frequencies of 600, 900, 2200, 3200, and 4800 Hz channels, as depicted in Fig. 1b. This new generation design has an active volume of 3 mm × 3 mm × 0.36 mm for each layer and a total active mass of 5.2 mg. The structure is compactly packaged with a total size of 3.5 mm × 3.5 mm × 1.52 mm and a total mass of 20.1 mg, staying below the loading limit of excess mass on ossicles during vibration. Unlike our previous sound sensor structures, the design was further optimized by reducing beam thickness to enhance the output levels of the sound sensor. This adjustment increased the stress levels on the PZT layer, enabling the sensor to generate ~300 mVpp output voltage under 100 dB SPL. The signal-to-noise ratio (SNR) of the channels of the transducer was measured in the absence of any input signal. SNR levels between 66.8 and 84.2 dB were obtained as a result. Table S1 displays the calculated SNR levels of the channels, noting that tests were not conducted in an anechoic chamber, and line noise on the system reduces actual performance, particularly at low frequencies.

The signal conditioning circuit, at the subsequent stage, utilized the voltage signals from the multichannel acoustic PZT sensor to build neural stimulation pulses31. One critical parameter of implantable systems is power consumption, which constrains the device’s operating time. Therefore, the signal conditioning circuit was primarily designed in current-mode to minimize power losses at current-to-voltage conversion and vice-versa, as shown in Fig. 1c. Another important parameter is the input dynamic range, which greatly affects speech perception. Daily sound levels range between 40 and 100 dB SPL16, and previous studies have demonstrated that a 50 dB input dynamic range provides adequate speech perception for multichannel cochlear implants32. Although the daily sound range is broad, the electrical dynamic range of the cochlea is about 20 dB32,33. Consequently, a low-power wide-range Logarithmic Amplifier (LA) is employed as the first stage to logarithmically compress the input sound range and amplify the limited amplitude of size constrained PZT sensors. Our amplifier can fit a 60 dB input dynamic range into ~15 dB (Fig. S1). The amplified current output of the LA is fed to an original multiplying current rectifier, which applies additional amplification in current mode. The output current of the rectifier at each channel is then filtered and sampled with a sample/hold circuit to generate a reference bias for the stimulation current generator that drives the auditory neurons with the required high currents. The current generator circuit also operates as a 7-bit digital to analog converter for the threshold and most comfortable level adjustment, enabling easy and wide-range control of the current by adjusting these digital signals. To ensure charge neutrality, the generated current is converted into a biphasic pulse via a switch matrix. The switch matrix targets the corresponding electrode (E1-E8) for each channel that matches the PZT sensor frequencies with auditory neurons. In order to further reduce the power dissipation, the LAs at each channel are powered down when inactive. The control unit generates power enable signals for the LAs, selection signals to switch between channels for sampling, and switch matrix control signals for 8-channel continuous interleaved sampling stimulation strategy, where each electrode is stimulated sequentially without any overlapping time to prevent interference between channels. The control unit is designed to accommodate different channel modes, allowing the system to operate at 1, 4, 6, or 8 channels and enabling user trade-offs between sound perception quality and power dissipation.

The power dissipation of the signal conditioning circuit while operating at 8-channel mode is below 600 µW, comparable with state-of-the-art FICI interface circuits, and enables long-lasting operation with an implantable battery. Power consumption of the interface circuit can be distributed as front-end signal conditioning, covering from logarithmic amplifier to the sample hold circuit, and the neural stimulation circuit, which is the most power-hungry part of the interface including the stimulation current generator and the switch matrix at the final stage. The power distribution of the FICI interface is 9.6 µW at the front-end signal conditioning circuit and 580.2 µW at the neural stimulation part with a typical biphasic rectangular current pulse. This power consumption can be further decreased by optimizing the stimulation pulse shape, which helps reduce the voltage compliance at the stimulation electrodes. Figure S2 presents the stimulation current and voltage on the electrode with a typical rectangular pulse shape that is applied in this study and an optimized exponential pulse shape where the voltage on the electrode is reduced by around 20% with the pulse shape optimization. The pulse shape optimization enables reducing the power consumption of the neural stimulation part to 460 µW with the reduced supply voltage. Therefore, the power consumption of the overall system can be kept below 500 µW while it is expected to achieve the neural stimulation threshold with a lower stimulation current level with the optimized exponential current pulse shape.

The implantable rechargeable batteries that can power the FICI interface are subject to international standards. A possible candidate for the full-custom FICI is Contego 50 mAh which is a Li-Ion implantable grade battery (ISO 13485) with a Titanium casing34. The 50 mAh capacity and 4.1 V voltage rating (205 mWh) of the battery allow more than 10 days of operation at 80% cycles when the FICI operates uninterruptedly all day. Contrary to conventional cochlear implants, which acquire power real-time using a coil pair, in FLAMENCO, wireless charging is applied. For charging the battery with an inductive coil link, there is a limitation regarding the maximum inductive power transferred to a tissue with respect to the part of the body where energy is transferred and generated heat around this tissue. According to these limitations, power density on the local head region cannot be larger than 10 W/kg when averaged over a 6-min period and cannot be larger than 20 W/kg for the duration of consecutive 10 s35. In addition, temperature rise is limited to 1 °C. In light of these limitations, the charging current is limited to 35 mA, meaning that the battery can be charged in less than 2 h.

In vitro validation of the FICI system

The hearing sensor was combined with a signal conditioning circuit and tested under different acoustic conditions to validate the sound sensing and electrical stimulation performance of the FICI. The acoustic PZT sensor was located on an artificial membrane that mimicked the eardrum. The input sound was applied through Etymotic Research ER-2 insert earphones, which were controlled by an audio amplifier, and the sound signal was generated by a signal generator. One of the earphones was plugged into the designated cavity, while the second was used to calibrate the sound levels. The acoustic sensor converted the incoming sound into voltage signals and is presented in Fig. 2a. Even at the lowest sound level (40 dB SPL) the sensor output was more than 150 μV, well above the input referred level of the signal conditioning circuit (10 μVrms), thus providing a high signal-to-noise ratio. The response for a combination of all 8 PZT sensor channels at a typical SPL (70 dB) that commonly occurs in daily life is given in Fig. S3. The channel bandwidths are wide enough to cover the full frequency band from 250 Hz to 6 kHz. The signal conditioning circuit sensed a wide range of input sound signals and provided a linear stimulation response to distribute the input sound signal to the electrical stimulation range of the cochlea. Figure 2b presents the sensing and neural stimulation response of the signal conditioning circuit with the acoustic sensor. The response showed that the FICI can capture sound signals between 45 and 100 dB SPL. For this test, a sound signal with 616 Hz, which corresponds to the resonance frequency of the second channel of the hearing sensor, was applied. The signal conditioning circuit generated a biphasic current pulse to stimulate auditory neurons, where the amplitude of the current varied according to the input sound level. The current pulses were generated at 21.1 Hz with 50 μs pulse width, which are typical values used for electrically evoked compound action potentials27. The stimulation frequency could also be tuned to 1 kHz, which is a typical value used in CI systems. For input sound ranges between 45 and 100 dB SPL, the system was able to generate stimulation currents in the range between 250 μA and 1 mA. The evenly distributed sound signals can vary from device to device; therefore, a 7-bit controller and a calibration circuit were added to arrange minimum-threshold and maximum-current levels for stimulation. This also provides patient fitting control to cover inter-recipient variability.

Fig. 2: In vitro characterization of piezoelectric sensor and signal conditioning circuit.
figure 2

a Acoustic piezoelectric sensor response of the second and seventh channels which have resonance frequency at 616 and 2931 Hz, respectively, where the responses were measured in the SPL range between 50 and 100 dB. The minimum detected sensor output was around 150 μV, above the minimum detection level of the signal conditioning circuit. b Generated neural stimulation current of the signal conditioning circuit at varying sound pressure level between 45 and 100 dB SPL. The stimulation current level varies between 250 μA and 1 mA and could be further extended using patient fitting control of the circuit.

Verification of the FICI using an in vivo animal model

Figure 3a presents the schematic representation of an in vivo experimental setup for the full-custom FICI system where the intracochlear electrodes were surgically placed in the cochlea of the animal model. The low profile PZT hearing sensor was mounted on a parylene membrane, placed on a sensor holder with a cavity 10 mm in diameter and 2 cm in length to mimic the ear canal23,36. The sound input of the system was provided through the Etymotic Research ER-2 insert earphones where the earphone was plugged into the designated cavity. The PZT sensor on the membrane converts the sound vibration into electrical signals, which are processed by the signal conditioning circuit. The signal conditioning circuit generates biphasic neural stimulation current pulses to activate the auditory neurons of the guinea pig through the intracochlear electrode array (MED-EL GmbH, Innsbruck, Austria), which was inserted through the round window into the scala tympani of the cochlea. The electrode array includes a reference electrode, placed extra tympanically on the bony wall of the bulla, and two stimulating intracochlear electrodes, which were inserted into the cochlea through the scala tympani. The stimulation electrodes were connected to the second and seventh channels of the FICI system and were tested with different frequencies to demonstrate the frequency selectivity of the system. The stimulation response was observed by the electrical auditory brainstem response (eABR) measurements, acquired via the optical amplifier and the Universal Smart Box of Intelligent Hearing Systems. Figure 3b shows an in vivo experiment setup used to validate the capability of the full-custom FICI system.

Fig. 3: Demonstration of the in-vivo experimental setup with an animal model.
figure 3

a Schematic representation of an in vivo experimental setup for the full-custom fully implantable cochlear implant system. where the intracochlear electrodes were surgically placed to the cochlea of the animal model. The piezoelectric sensor was mounted on a parylene membrane, which is placed on a sensor holder that has a cavity with 10 mm diameter and 2 cm length to mimic the ear canal. The sound input of the system was provided to the cavity through the Etymotic Research ER-2 insert earphone. The piezoelectric sensor outputs are processed by the signal conditioning circuit and generates biphasic current pulses to stimulate auditory neurons of the guinea pig. The current pulses are provided through an intracochlear electrode array which was inserted through the round window into the scala tympani of the cochlea. The stimulation response was observed by the electrical auditory brainstem response (eABR) measurements, acquired via the optical amplifier and the Universal Smart Box of Intelligent Hearing Systems (HIS). b The full-custom FICI system under the in-vivo tests on an animal model which also shows the surgically placed intra-cochlear stimulation electrodes.

In order to validate the system performance, eABR responses of six ears of Hartley guinea pigs (one ear of four animals and both ears of an animal were used) were tested and analyzed. Before measuring eABR responses, ototoxic deafening was performed to reduce the electrophonic activity in the eABR. Ototoxic deafening was achieved by administrating 600 mg/kg kanamycin (Kanovet, Vetaş, İstanbul, Turkey) by intramuscular injection and 75 mg/kg intraperitoneal furosemide (Lasix; Avetis Pharma, Istanbul, Turkey) after 1 hour once a week27,37,38. The deafening process of the guinea pigs was observed by checking the click and tone burst stimulus-evoked ABR responses. Figure 4a shows the response of an animal with normal hearing whereas Fig. 4b represents the response after ototoxic deafening was performed to that animal.

Fig. 4: In vivo experiment results with different sound levels.
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a Representative acoustic auditory brainstem response (ABR) waves with click stimulus (8–10 kHz) in a guinea pig with normal-hearing before the deafening protocol. The stimulus was presented at a frequency of 21.1 pulses per second with 512 repetitions. Stimuli level 30–90 dB sound pressure level (SPL) is shown in 10 dB steps. Roman numeral denotes ABR wave number. The wave amplitudes and latency increase and decrease, respectively, with increasing dB SPL. b Representative acoustic ABR waves with click stimulus (8–10 kHz) in a deafened guinea pig after the deafening protocol. The stimulus is presented at 21.1 pulses per second with 512 repetitions. Stimuli level 90 dB SPL is shown for two different recordings. c Representative electrical auditory brainstem response (eABR) waves to FICI stimulation in a deafened guinea pig at the second channel of the piezoelectric sensor with pure-tone acoustic stimuli at 616 Hz, which is the corresponding resonance frequency. A biphasic pulse train is presented to electrode #1 in monopolar configuration at 21.1 pulses per second with 512 repetitions. Stimuli level 40–100 dB SPL is applied in 10 dB steps. The wave amplitudes and latency increase and decrease, respectively, with increasing dB SPL. d Representative eABR waves to FICI stimulation in a deafened guinea pig at the second channel of the ABR with pure-tone acoustic stimuli at 2922 Hz, which is an off-resonance frequency of the cantilever. As expected, no response was observed from the eABR recording at the off-resonance stimulation. e Representative eABR waves to FICI stimulation in a deafened guinea pig at the seventh channel of the PZT sensor with pure-tone acoustic stimuli at 2922 Hz, which is the corresponding resonance frequency. A biphasic pulse train is presented to electrode #2 in monopolar configuration at 21.1 pulses per second with 512 repetitions. Stimuli level 40–100 dB SPL is shown in 10 dB steps. The wave amplitudes and latency increase and decrease, respectively, with increasing dB SPL. f Injected charge level at each pulse phase of the FICI stimulation in a deafened guinea pig which is excited with pure-tone acoustic stimuli.

FICI system can evoke eABRs

The auditory brainstem response (ABR) is a compound action potential evoked in response to transient auditory stimuli, typically clicks or tone bursts. It is characterized by a series of waves representing different stations along the auditory pathway. Wave II was quantified in the analysis, because the peak and trough of Wave II were reliably evoked by acoustic stimuli and electrical pulse shapes applied to the guinea pig. To verify whether FICI system pulses could generate an electrically evoked ABR (eABR), the system was applied to guinea pig, and its eABRs were measured at varying SPLs.

Figure 4c depicts the eABR recordings with acoustic stimulation from 40 to 100 dB SPL at 616 Hz, which is the resonance frequency of the second channel of the PZT sensor. A stimulus artifact in the eABR recording occurred at the onset of the stimulus. Response recordings between 4–6 ms may be affected by digastric muscle response. The eABR recordings of four deafened guinea pigs (one from both ear) is presented in Fig. S4. The mean eABR peak latency of Wave II was 1.37 ± 0.15 ms (n: 6) and the mean magnitude of the Wave II is observed as 0.78 ± 0.55 µV (n: 6). Decreasing stimulus level resulted in reduced amplitudes and prolonged peak latency. As expected, this effect on latency increased systematically from Wave I to IV. As a result, the threshold of the FICI system was recorded as 45 dB SPL, considering the Wave II. Although electrical artifact occurred at lower input sound levels, no eABR response was observed, indicating that generated charge was not enough for excitation.

For further confirmation of the frequency selectivity, the second and seventh channels of the PZT sensor were subjected to the same experiment with acoustic stimuli at 616 Hz (resonance frequency of the second channel) and 2931 Hz (resonance frequency of the seventh channel). The frequency selectivity of the PZT sensor was assessed by measuring eABR recording while connecting respective output channel of the signal conditioning circuit to the intracochlear electrode. The designed system generated stimulation pulses only if the input sound frequency matched the frequency band of the corresponding channel. When an off-resonance frequency of the corresponding channel was applied, no stimulus artifacts or responses were observed in the eABR recordings. Figure 4d presents the measured eABRs using the second channel of the PZT sensor while applying a pure-tone sound at 2931 Hz. Since it was insensitive to off-resonance frequencies, the cantilever generated a very low output to initiate electrical stimulation from the signal conditioning circuit. Similarly, the stimulation performance for the seventh channel at its resonance frequency (2931 Hz) is given in Fig. 4e, which also has its threshold level as 45 dB SPL. The off-resonance response of the seventh channel was similar to the one shown in Fig. 4d. Figure 4e shows the amplitude of Wave II as a function of the input sound level. The amplitude of Wave II increased with the level of input sound pressure sensed by the PZT sensor. These eABR recordings clearly demonstrate that the FICI system could electrically stimulate auditory neurons using input acoustic stimuli. Figure 4f depicts the correspondence in the relation between input sound levels and injected charge.