Periodic Reporting for period 4 - FLAMENCO (A Fully-Implantable MEMS-Based Autonomous Cochlear Implant) Reporting period: 2021-01-01 to 2022-06-30 Summary of the context and overall objectives of the project Today, congenital or acquired hearing loss affects around 5% (360 million people, of which 32 million are children, WHO, 2015) of the world population and presents significant impact on people’s social, emotional, and economic wellbeing. Deafness is a partial or total inability to hear, and classified as conductive, sensorineural, and mixed deafness. Sensorineural impairment, which represents the majority of the profound deafness, can be restored using cochlear implants (CIs), which electrically stimulate the auditory nerve to repair hearing in people with severe-to-profound hearing loss (>90 dB sound pressure level in both ears). CIs are used for more than 40 years and today implanted in around 500.000 individuals worldwide. However, conventional CIs have major drawbacks such as replacing the entire natural hearing mechanism with electronic hearing, even though most parts of the hearing system (such as the eardrum and ossicles) are operational. Moreover, daily battery recharge/replacement requirement, damage risk of external components especially if exposed to water (shower, rain, swimming, perspiration etc.), aesthetic concerns particularly for children and young adults, limitation in access to some medical examinations and treatments, personal safety and interrupted communication during night time are other critical drawbacks. Therefore, researchers in this area try to eliminate these problems via fully implantable, self-powered, and stand-alone cochlear implants.FLAMENCO project was aimed to develop a fully implantable, low-power, energy harvesting, next generation CI mimicking the natural hearing mechanism of the ear. Fully Implantable Cochlear Implant (FICI) proposed by FLAMENCO has a ground-breaking nature as it revolutionizes the operation principle of the conventional CIs. In this respect, we developed novel transducers for sound sensing and energy harvesting, and interface electronics for processing the signals generated by these transducers. In parallel, packaging and interconnects were implemented, followed by the integration of sub-units for mechanical, electronic and in-vivo tests. These tests on the sub-units and integrated systems of FICI revealed the achievement of the highest efficiency energy harvesting IC, lowest power consuming sound processing IC; and minimum mass sound sensor achieving the highest voltage output in the literature. We also succeeded in; stimulating auditory system of a deafened guinea pig; and generating intelligible outputs during speech tests. All of these achievements are considered to be significant results for advancing to preclinical validation and performing further R&D aiming at commercialization of FLAMENCO FICI Concept.In conclusion, we are confident that FLAMENCO has the potential to eliminate the aforementioned concerns for actual CI technology and improve the lives of people with sensorineural impairment by recovering their hearing as good as healthy individuals. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far FLAMENCO project was composed of development of transducers, interface electronics and integration structures followed by testing of each unit and integrated systems. Briefly, most of the objectives are realized and the concept has been verified successfully.Transducer development started with modelling of energy harvester (EHs), sound sensors and vibration characteristics of the middle ear elements. We employed piezoelectric cantilevers for both sound sensor and energy harvester. The sound sensor with multi-channel single layer structure significantly minimized the mass while achieving the highest voltage output in the literature. On the other hand, the highest power density among acoustic EHs in the literature is observed.We developed and fabricated multiple designs of flexible parylene substrate (providing biocompatibility) for the integration of transducers and interface circuits. In the scope of integrated circuit (IC) development for the FICI, four (4) generations of sound ICs were designed with novelties resulting in; outstandingly low power consumption, high input dynamic range, digital patient fitting, high sensitivity, successful mimicking of natural hearing mechanism and satisfactory stimulation performance. Similarly, four generations of EH ICs were also designed, achieving high power efficiency. Magnet-free wireless transmission for patient fitting and battery recharging are also integrated to the device.Finally tests of transducers and interface electronics were performed. Sound sensors and EHs were tested on shaker table and on artificial tympanic membrane giving the highest output compared to similar transducers in the literature. The power dissipation and efficiency of ICs showed that the targets are achieved. Performance of the transducer unit with interface circuits is investigated under different acoustic conditions to validate the sound detection and electrical stimulation performance. The tests showed that the FICI can sense and process typical daily hearing range successfully. After laboratory tests, whole system is verified with animal tests by stimulating the cochlea of guinea pigs via an implanted electrode. Results of the tests revealed that the proposed FLAMENCO FICI is feasible for advancing to preclinical validation and performing further R&D. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) FLAMENCO has a ground-breaking nature due to its revolutionary operation principle. Progress by the end of the project revealed that the novel concept proposed by FLAMENCO; fully implantable, low-power, energy harvesting, next generation CI mimicking the natural hearing mechanism of the ear is feasible. As the most unique feature, the proposed CI benefits middle ear vibrations through a mechanical sensor based on frequency selective piezoelectric cantilevers covering the human hearing band. MEMS based acoustic sensor, implemented as single layer to cope with weight and volume limitations of the middle ear, performed an outstanding sensitivity. This novel approach eliminates most of the power-hungry electronics, while keeping the healthy portions of the middle ear functional. To process the sensor output and stimulate the auditory neurons, a novel power-efficient IC is developed and validated by in-vivo tests. This IC is the first FICI interface utilizing patient fitting and active charge balancing while achieving highest input dynamic range and lowest power dissipation in the literature. This outstanding performance creates a paradigm shift in the operation principle of the conventional CIs.Additionally, the FICI has an energy harvester (EH) for battery recharging. The EH transducer is a single piezoelectric cantilever working in a narrow acoustic band specifically reserved for harvesting; hence the daily hearing is not affected. The success in developing ultra-low power electronics for energy harvesting may pave the pathway for low-power biomedical implants.In summary, both the whole implant system and every single internal block can be described as a breakthrough or as advancing a research field significantly beyond the state of the art. Namely the acoustic transducers, energy harvesters, ultra-low power interface electronics, and packaging/implantation bring significant advancement and novelty to the related fields. Implant integrated on the ear model Schematic view of the overall system and Transducer Packaging Micrograph and layout view of the Interface Circuits Picture of FLAMENCO Transducers and IC
