Abstract
ESTROSA: Energy-autonomous System for TReatment of Obstructive Sleep Apnea Obstructive Sleep Apnea (OSA) is a complex and chronic respiratory disorder characterized by partial or complete obstruction of the upper airways during sleep, which leads to a significant reduction in airflow despite continued respiratory effort. This condition results in intermittent hypoxia, fragmented sleep, and a consequent drop in hemoglobin saturation, with systemic effects that can compromise cardiovascular, metabolic, and cognitive health. Current treatment options, such as CPAP (Continuous Positive Airway Pressure), although effective, are often poorly tolerated or suboptimal in the long term, particularly in pediatric or neurological patients. To address this unmet clinical need, ESTROSA project (Energy-autonomous System for TReatment of Obstructive Sleep Apnea) proposes a radically innovative approach to the treatment of OSA. The core idea is to develop, validate, and implement an implantable, energetically autonomous microsystem capable of modulating the neural activity responsible for maintaining airway patency. This system is based on optogenetic stimulation techniques applied to genetically modified neurons expressing light-sensitive ion channels, and on a Wireless Power Transfer (WPT) platform that eliminates the need for batteries, thus enhancing miniaturization and biocompatibility. From a biological standpoint, the project focuses on directly stimulating the hypoglossal nuclei, which represent the motor control center for tongue muscles; the goal is to induce a controlled and global (antero-posterior and bilateral) contraction of the tongue, promoting the stabilization of the upper airway during sleep and reducing the number and severity of apneic episodes. The optogenetic strategy used in ESTROSA enables selective neuronal activation with temporal precision, minimizing off-target effects and improving therapeutic specificity. By coupling this technique with a closed-loop system, the stimulation can be activated only when needed, i.e., in response to a detected drop in blood oxygen saturation. This intelligent feedback mechanism significantly increases the system’s efficiency and reduces unnecessary neural stimulation, contributing to a more physiological and adaptive therapy. From an engineering perspective, the core innovation of ESTROSA lies in the development of a miniaturized, battery-less implantable device. The architecture of this device includes: i) a receiving coil operating in the MHz range, designed for near-field magnetic coupling. The coil will be fabricated using flexible substrates (e.g., polyimide or PDMS) to allow conformal integration under the skin of the mouse; ii) rectifier circuit that converts the AC RF signal into a stable DC voltage, supplying energy to the control electronics and the optical emitter; iii) an ultra-low-power microcontroller for real-time control of the μ-LED based on input from external signals or internal physiological sensors (e.g., oximeters); iv) a μ-LED (micro-light-emitting diode) tuned to the activation wavelength of the opsins expressed in the genetically modified neurons, capable of delivering localized light with high spatial precision; v) a wired connection from the subcutaneous coil to the cranial implantation site for light delivery, ensuring minimal invasiveness while maintaining high efficiency. In the transmitting unit, a key design feature is the creation of a 3D magnetic field distribution within the animal cage, achieved through a tri-axial coil system. This configuration maximizes the link efficiency between the transmitter and the receiver regardless of the animal’s orientation or position, a fundamental requirement for preclinical studies conducted in freely moving mice. The link budget analysis, including estimations of coupling coefficients, Q-factors, impedance matching, and power margins, will define the optimal transmission parameters to reliably energize the implanted device. Another crucial component of the ESTROSA project involves characterizing the electromagnetic interaction with biological tissues. This includes the extraction of the complex dielectric permittivity (real and imaginary parts) of the mouse tissues in the relevant frequency range, using dielectric spectroscopy techniques. This data will be integrated into full-wave electromagnetic simulations to model the propagation and absorption of the electromagnetic fields within the mouse body. This characterization will enable accurate estimation of the Specific Absorption Rate (SAR), a key parameter for assessing thermal safety and regulatory compliance. By keeping SAR levels well below the limits set by standards, the project ensures the feasibility of chronic implantation and repeated activation without adverse effects on tissue integrity or animal welfare. In parallel, the project encompasses in-vitro and in-vivo experimental validations. Specifically, in-vitro testing will be carried out on the optogenetic micro-devices and the oximeter unit, to validate spectral emission, power consumption, heat dissipation, and sensitivity under controlled laboratory conditions. In-vivo validation will focus on wireless acquisition of neurophysiological signals, including electroencephalogram (EEG) and electromyography (EMG), to monitor brain activity and muscle responses during sleep. This will allow the evaluation of therapeutic efficacy and the correlation between optogenetic stimulation and apnea mitigation. The convergence of these biological, electronic, and system-level innovations positions ESTROSA as a cutting-edge multidisciplinary platform for next-generation bioelectronic medicine. It combines precision neuromodulation, wireless microsystems, low-power circuit design, and biological signal processing into a single integrated system for the treatment of a widespread but still challenging pathology. In conclusion, ESTROSA introduces a paradigm shift in the treatment of OSA by leveraging optogenetics and wireless engineering. It is expected to offer an unprecedented level of control and safety in neural stimulation, enabling future developments not only in respiratory medicine but also in other domains of neuroscience, such as motor disorders, epilepsy, or neuroprosthetics. The miniaturized, battery-less architecture opens the door to truly chronic implants, unlocking the potential of energy-autonomous closed-loop biointerfaces. Through its innovative approach, ESTROSA aims to pave the way for a new era in personalized, adaptive, and minimally invasive neurotherapeutics.
Dettagli del progetto
Responsabile scientifico: Giacomo Paolini
Strutture Unibo coinvolte:
Dipartimento di Ingegneria dell'Energia Elettrica e dell'Informazione "Guglielmo Marconi"
Coordinatore:
ALMA MATER STUDIORUM - Università di Bologna(Italy)
Contributo totale di progetto: Euro (EUR) 244.004,00
Contributo totale Unibo: Euro (EUR) 122.162,00
Durata del progetto in mesi: 24
Data di inizio
30/11/2023
Data di fine:
28/02/2026
