A Frequency-Switching Inductive Power Transfer System for Wireless, Miniaturised and Large-Scale Neural Interfaces

G. L. Barbruni; C. Cordara; M. Carminati; S. Carrara; D. Ghezzi

Three-coil inductive power transfer is the state-of-the-art solution to power multiple miniaturised neural implants. However, the maximum delivered power is limited by the efficiency of the powering link and safety constrains. Here we propose a frequency-switching inductive link, where the passive resonator normally used in a three-coil link is replaced by an active resonator. It receives power from the external transmitter via a two-coil inductive link at the low frequency of 13.56 MHz. Then, it switches the operating frequency to the higher frequency of 433.92 MHz through a dedicated circuitry. Last, it transmits power to 1024 miniaturised implants via a three-coil inductive link using an array of 37 focusing resonators for a brain coverage of 163.84 mm(2). Our simulations reported a power transfer efficiency of 0.013% and a maximum power delivered to the load of 1970 mu W under safety-constrains, which are respectively two orders of magnitude and more than six decades higher compared to an equivalent passive three-coil link. The frequency-switching inductive system is a scalable and highly versatile solution for wireless, miniaturised and large-scale neural interfaces.

DOI : 10.1109/TBCAS.2024.3359481

A Wearable Real-Time System for Simultaneous Wireless Power and Data Transmission to Cortical Visual Prosthesis

G. L. Barbruni; F. Rodino; P. M. Ros; D. Demarchi; D. Ghezzi  et al.

Wireless, miniaturised and distributed neural interfaces are emerging neurotechnologies. Although extensive research efforts contribute to their technological advancement, the need for real-time systems enabling simultaneous wireless information and power transfer toward distributed neural implants remains crucial. Here we present a complete wearable system including a software for real-time image capturing, processing and digital data transfer; an hardware for high radiofrequency generation and modulation via amplitude shift keying; and a 3-coil inductive link adapt to operate with multiple miniaturised receivers. The system operates in real-time with a maximum frame rate of 20 Hz, reconstructing each frame with a matrix of 32 x 32 pixels. The device generates a carrier frequency of 433.92 MHz. It transmits the highest power of 32 dBm with a data rate of 6 Mbps and a variable modulation index as low as 8%, thus potentially enabling wireless communication with 1024 miniaturised and distributed intracortical microstimulators. The system is primarily conceived as an external wearable device for distributed cortical visual prosthesis covering a visual field of 20(degrees). At the same time, it is modular and versatile, being suitable for multiple applications requiring simultaneous wireless information and power transfer to large-scale neural interfaces.

DOI : 10.1109/TBCAS.2024.3357626

In-Memory Sensing and Computing for Cancer Diagnostics: A Perspective Paper

S. Carrara; J. Chen; K. Bhardwaj; A. Golparvar; G. L. Barbruni

During the past two decades, a number of two-terminal switching devices have been demonstrated in the literature. They typically exhibit hysteric behavior in the current-to-voltage characteristics. These devices have often been also referred to as memristive devices. Their capacity to switch and exhibit electrical hysteresis has made them well-suited for applications such as data storage, in-memory computing, and in-sensor computing or in-memory sensing. The aim of this perspective paper is to is twofold. Firstly, it seeks to provide a comprehensive examination of the existing research findings in the field and engage in a critical discussion regarding the potential for the development of new non-Von-Neumann computing machines that can seamlessly integrate sensing and computing within memory units. Secondly, this paper aims to demonstrate the practical application of such an innovative approach in the realm of cancer medicine. Specifically, it explores the modern concept of employing multiple cancer markers simultaneously to enhance the efficiency of diagnostic processes in cancer medicine.

DOI : 10.1109/TBCAS.2023.3334144

Bodily implant microelectrode and bodily implant microelectrode fabrication method

G. L. Barbruni; D. Ghezzi; S. Carrara

The present invention concerns a bodily implantable or probe device and microelectrode fabrication method comprising providing at least one silicon substrate including an electronic device or unit; providing, on a first side of the silicon substrate, at least one conducting material for forming at least one elongated electrical channel of the microelectrode; providing an insulator material on the conducting material to define at least one active site or area of the microelectrode, providing a protection material or layer onto the first side of the silicon substrate or layer; etching the silicon material of a second side of the silicon substrate to form at least one elongated projection extending away from the silicon substrate, the elongated projection comprising the conducting material, and expose an elongated surface of the conducting material of the elongated projection; removing the protection material or layer from the first side of the silicon substrate; and providing a further insulator material on the exposed elongated surface of the conducting material to isolate the elongated electrical channel of the at least one microelectrode, and providing the further insulator material on the etched at least one silicon substrate.

A modular multiple frequency inductive link to wirelessly power multiple miniaturized implants

G. L. Barbruni; D. Ghezzi; S. Carrara

A modular multiple frequency coils inductive link system to wirelessly provide power for at least a medical implant at an output of a receiving coil, whereby the receiving coil is configured to be implanted in an organism. The modular multiple frequency coils inductive link comprises a transmitter coil configured to input power from a power supply and induce a first magnetic field at a resonating carrier frequency. The modular multiple frequency coils inductive link further comprises a shifting resonator comprising at least an active integrated circuit, a first coil configured to receive the first induced magnetic field from the transmitter coil by induction at the resonating carrier frequency and convert it to an electrical current, and a second coil configured to transmit the electrical current to the receiving coil by inducing a second magnetic field at a determined frequency different from the resonating carrier frequency, the active integrated circuit connected with both the first coil and the second coil and being configured to receive the power induced at the resonating carrier frequency though the first coil and to use it to drive remaining power reduced due to a power dissipation of the active integrated circuit at the determined frequency though the second coil. The receiving coil is configured to receive the power induced by the second coil at the determined frequency and make it available at the output of the receiving coil.

A Novel Piezoresistive Microcantilever Structure for Free Valproic Acid Sensing in Personalized Epilepsy Management

A. A. A. Abbas; J. Qian; G. L. Barbruni; A. Golparvar; A. Kapic  et al.

Microcantilever-based biosensors have emerged as promising technologies for point-of-care sensing systems. However, since they are typically utilized as a single piezoresistor in a quarter Wheatstone bridge configuration, they suffer from output asymmetry and require rigorous calibration to eliminate their common-mode interference. In this study, we propose a novel piezoresistive double-clamped beam structure in a half-Wheatstone bridge configuration, which offers a highly accurate biosensing approach for measuring the levels of free valproic acid (fVPA) in biological samples. The sensor design incorporates two active piezoresistors, resulting in improved measurement accuracy by providing balanced recordings. This balanced configuration allows for automatic compensation of environmental parameters and enhances the robustness of recordings against common signal interferences such as temperature variations. In addition, this new biosensing mechanism offers a lower limit of detection, enabling precise measurements within the entire therapeutic range of fVPA. To assess the sensor efficacy under various experiment conditions, in-silico simulations were conducted. The simulation results demonstrated the remarkable potential of the new sensor for use in point-of-care settings.

DOI : 10.1109/JSEN.2023.3319021

New Insights Into the I/V Hysteretic Characteristics of Memristive Biosensors

K. Bhardwaj; A. Golparvar; J. Chen; G. L. Barbruni; S. Carrara

Over the past decade, significant advancements have been made in the study of silicon nanowires (SiNWs). These nanoscaled devices can exhibit a memristive type of hysteresis in the current/voltage (I/V) plane that has been utilized in the biosensors leading to exceptional sensitivities up to the femto levels. Here we investigate the memristive properties of SiNW-based biosensors in their unmodified state, as well as after surface biofunctionalization with aptamers. The development of SiNWs involved a top-down nanofabrication approach, resulting in nanowires with 100 nm wide and 1 mu m long. Later, biofunctionalization was performed through controlled drop casting. The experimental findings obtained in this study demonstrate for the first time that different SiNWs from the same fabrication batch can exhibit diverse memristive switching phenomena in the I/V plane. These phenomena encompass both volatile noncrossing memristive behavior as well as nonvolatile crossing memristive responses. Furthermore, we demonstrate that the I/V hysteresis exhibited by biofunctionalized nanowires is determined by their inherent memristive characteristics and the induced capacitive effect. Drawing upon these new findings, a simple mathematical simulation model of the Memristive biosensor is developed and evaluated in SPICE.

DOI : 10.1109/LSENS.2023.3301840

Changes Over Time in the Electrode/Brain Interface Impedance: An Ex-Vivo Study

L. Iannucci; G. L. Barbruni; D. Ghezzi; M. Parvis; S. Grassini  et al.

Closed-loop neural implants based on continuous brain activity recording and intracortical microstimulation are extremely effective and promising devices to monitor and address many neurodegenerative diseases. The efficiency of these devices depends on the robustness of the designed circuits which rely on precise electrical equivalent models of the electrode/brain interface. This is true in the case of amplifiers for differential recording, voltage or current drivers for neurostimulation, and potentiostats for electrochemical bio-sensing. This is of paramount importance, especially for the next generation of wireless and ultra-miniaturised CMOS neural implants. Circuits are usually designed and optimized considering the electrode/brain impedance with a simple electrical equivalent model whose parameters are stationary over time. However, the electrode/brain interfacial impedance varies simultaneously in frequency and in time after implantation. The aim of this study is to monitor the impedance changes occurring on microelectrodes inserted in ex-vivo porcine brains to derive an opportune electrode/brain model describing the system and its evolution in time. In particular, impedance spectroscopy measurements have been performed for 144 hours to characterise the evolution of the electrochemical behaviour in two different setups analysing both the neural recording and the chronic stimulation scenarios. Then, different equivalent electrical circuit models have been proposed to describe the system. Results showed a decrease in the resistance to charge transfer, attributed to the interaction between biological material and the electrode surface. These findings are crucial to support circuit designers in the field of neural implants.

DOI : 10.1109/TBCAS.2023.3284691

A Front-End CMOS Interface Circuit With High Voltage Charge Pump and Oscillator for Capacitive Micromachined Ultrasonic Transducers

Y. Zhao; G. L. Barbruni; Z. Li; L. Zhao; X. Wang  et al.

Label-free biosensors, combined with miniaturized micro-electromechanical sensory platforms, offer an attractive solution for real-time and facile monitoring of biomolecules due to their high sensitivity and selectivity without the need for specifically labeling. Resonators have been acknowledged as an efficient technology for measuring biomolecular binding events including those involving nucleic acid and antibody. Among these, capacitive micromachined ultrasonic transducers (CMUTs) have emerged as a promising candidate for biosensing. However, their usage is often limited by the requirement for high voltage supply and continuous frequency tracking, which can result in significant parasitic effects and measurement errors. In this brief, we present a novel front-end interface circuit for a CMUTs-based biosensor. The circuit, fabricated using TSMC 0.18-mu m BipolarCMOS-DMOS (BCD) technology, incorporates an on-chip high voltage charge pump and feedback frequency monitoring. The CMUTs array features 20 x 20 circular cells, fabricated using a low-temperature direct bonding technology, with an experimental parallel-resonant frequency of 1.724 MHz and a high quality factor of up to 40.9. To fit the measured electrical characteristics, a five-element equivalent lumped element model is proposed. The high voltage charge pump provides an output voltage of similar to 20 V, while the feedback oscillator has a ms-level start-up time and a total power dissipation of 3.8 mW. The proposed frontend interface is designed to function as a stand-alone chip for CMUTs-based resonant biodetection.

DOI : 10.1109/TCSII.2023.3261061

Amperometric Urine Biosensor for Rapid Point-of-Care Tuberculosis Diagnosis

C. Delgrange; A. Fulciniti; T. Veske; R. Peseux; A. Kapic  et al.

In this study, we propose the development and simulation of an electrochemical aptamer biosensor designed for point-of-care detection of tuberculosis (TB) in human urine. The biosensor operates through amperometric biosensing combined with aptamer-antibody sandwich assays using the TB-antigen CFP-10. Theoretical calculations conducted in this research demonstrate the potential for highly sensitive and accurate read-out, with a linear range of 0.17-0.53 nA, covering concentrations from 3 to 10 nM. Furthermore, the incorporation of an Slayer filter enables efficient sample filtration, enhancing the sensitivity and selectivity of the biosensor for detecting TB during urination events without the need for professional healthcare assistance. Therefore, this system is well-suited for deployment outside the laboratory, particularly in resource-limited settings or underdeveloped regions.

Miniaturised, Wireless and Distributed Neural Interface Toward Cortical Visual Prosthesis

G. L. Barbruni

Over the last decades, implantable neural interfaces have been extensively explored and effectively deployed to address neurological and mental health disorders. The existing solutions present several limitations. Firstly, the physical size of the implantable device remains bulky, primarily due to the inclusion of batteries. Second, the presence of cables significantly hamper biomechanical compliance, restrict the maximum number of channels and make the surgical procedure inherently complex. Wireless power transfer and CMOS miniaturisation are key factors in addressing those limitations. Up to date, the smallest wireless neurostimulator relies on 3-coil inductive link and delivers ±25 µA in a total area of 650x650 µm2. However, the system cannot continuously operate complying within safety standards, the maximum current is limited, and the manual electrode integration reduces the total yield. Hence, an imperative demand exists for innovative solutions enabling system miniaturisation by safely exploiting wireless power transfer and communication while allowing sufficient charge injection capabilities. In this thesis, a miniaturised, wireless, and distributed neural interface is ideated and developed envisioning a large-scale cortical prosthesis with thousands of free-standing and individually addressable implants. A novel frequency-switching inductive link is proposed to overcome safety and performance limitations of traditional systems. Preliminary results show an improved efficiency and delivered power respectively of two orders of magnitudes and more than six decades compared with state-of-the-art 3-coil links while working with 1024 receivers with the up-to-date smallest size of 200x200 µm2. As a significant advancement, the introduced "Neural Dot" envisions a fully integrated monolithic chip including the receiver coil as well as the analog and digital functions. All the CMOS blocks are individually tested, showing the smallest power manager and the smallest biphasic current-controlled stimulator capable of delivering train of bursts of ±40 µA with a limited harvested power budget at the rectifier input. Circuit design is co-optimized with the electrode/brain interface, engineering the Pt-black coating material and studying the effect of the bioimpedance changes over time by proposing a non-stationary model for robust circuit co-optimization. A novel electrode microfabrication technique relying on CMOS-compatible post-processing at the wafer level is proposed to address the traditional challenges in integrating the electrodes with miniaturised chips. This "foundry-to-surgeon" approach envisions a multi-shank and multi-channel scalable and large-scale neural interface. All the investigations were carried out toward a large-scale cortical visual prosthesis, for which every single CMOS stimulating unit corresponds to a phosphene perceived in a precise spatial location of the blind visual field. In vivo studies with non-human primates were conducted to derive the main trade-off among the stimulation parameters for developing and co-optimizing the miniaturised CMOS unit, representing an effort well beyond the present state-of-the-art for both area consumption and power budget. The preliminary results motivate further investigation and development as the proposed solutions are promisingly addressing several critical issues commonly encountered today, thus opening new frontiers for treating neurodegenerative and mental health disorders.

An Ultra-Miniaturised CMOS Clock and Data Recovery System for Wireless ASK Transmission

M. Cerbai; G. L. Barbruni; P. M. Ros; D. Demarchi; D. Ghezzi  et al.

Over the years, several clock and data recovery architectures have been proposed for wireless Amplitude Shift Keying (ASK) transmitted signals. State-of-the-art architectures mainly rely on synchronous phase-locked loop circuits or selfsampling systems, both resulting in large area consumption. This work presents a novel CMOS architecture for Clock and Data Recovery (CDR) in miniaturised and wirelessly powered implants. The proposed CDR architecture works at 433.92 MHz and includes: an ASK-demodulator, an on-chip oscillator, a power-on-reset, a control and a recovering block operating in feedback-loop. The ASK-demodulator works for a data rate as high as 6Mbps and a modulation index in the range of 9-30%. A novel communication protocol is presented for a separated clock and data transmission. The entire CDR architecture occupies 17 x 89 mu m(2) and consumes 15.01 mu W while operating with a clock rate of 6 Mbps.

A Novel Approach in Edge Computing: In-Memory Sensing of Cancer Markers

D. Heim; G. L. Barbruni; S. Carrara

We present here the first ever-reported direct computation of the cancer risk on cancer markers simultaneously detected by memristors. The novel approach in cancer diagnostics here proposed is based on the fusion of the three actions of sensing, computing and memory in a single-kind of device. So, this paper proposes the new concept of in-memory sensing as a disruptive approach in edge-computing. The concept is demonstrated by showing a well-known case in cancer diagnostics: the estimation of the risk of prostate cancer based on the simultaneous measure of Prostate Specific Antigen (PSA) and its Membrane isoform (PSMA).

Ultra-Miniaturised CMOS Current Driver for Wireless Biphasic Intracortical Microstimulation

G. L. Barbruni; P. M. Ross; D. Dernarchit; S. Carrara; D. Ghezzi

This work shows an ultra-miniaturised and ultra-low-power CMOS current driver for biphasic intracortical microstimulation. The CMOS driver is composed of a leakage-based voltage-to-current converter and an H-bridge circuit providing biphasic charge-balanced current stimulation. The circuit has been simulated, fabricated and tested. The current driver consumes 1.87 mu W with a supply voltage of 1.8 V, and it occupies a silicon area of 15X12.4 mu m(2) . The driver works in linearity in the current range between 23-92 mu A.

A 20 Mbps, 433 MHz RF ASK Transmitter to Inductively Power a Distributed Network of Miniaturised Neural Implants

G. L. Barbruni; F. Asti; P. M. Ros; D. Ghezzi; D. Demarchi  et al.

Simultaneous wireless information and power transfer is an emerging technique in neurotechnology. This work presents an efficient transmitter for both power transfer and downlink data communication to multiple, miniaturised and inductively-powered chips. We designed, implemented and tested a radio-frequency transmitter operating at 433.92 MHz of the industrial, scientific and medical band. A new structure is proposed to efficiently modulate the carrier, exploiting an amplitude-shift keying modulation reaching a data rate as high as 20 Mbps together with a variable modulation index as low as 8%.

Equivalent Circuit Analysis of CMUTs-based Device for Measurement in Liquid Samples

Y. Zhao; L. Zhao; G. L. Barbruni; Z. Li; Z. Jiang  et al.

Capacitive micromachined ultrasonic transducers (CMUTs) operating at the series and parallel resonant frequencies, have shown a great potential in ultrasonic application and in biodetection. However, previous equivalent circuits rarely consider the fitting performance and measurement. This study proposes the establishment of the simplified equivalent circuits for the CMUTs-based device to analyze the electrical properties and the measurement sensitivity in liquid environment. We simulate a circular CMUT cell both in air and water through finite element method via COMSOL software, exploiting the multi-domain coupling method. We analyze the impedance behaviors of the CMUTs array with 100 cells under different direct current bias voltages (2 - 10V). Simultaneously, we successfully investigate the damping effects on the electrical characteristics such as impedance, phase, and quality factor. With the 4-element Butterworth-vanDyke model, two simplified equivalent lumped element models (LEMs) are demonstrated to fit the impedance curves of the CMUTs array around the series and parallel frequencies, respectively. Additionally, the sensitivity is evaluated using the simplified equivalent LEMs to explore the CMUTs array has a high normalized measurement sensitivity of 6.024 ppb/Hz at the parallel frequency.

From 0.18 mu m to 28nm CMOS Down-scaling for Data Links in Body Dust Applications

G. L. Barbruni; S. Carrara; P. M. Ros; D. Demarchi

In this work, we study the effect of transistor downscaling in a wireless communication circuit for Body Dust application. The system requires a chip lateral size smaller than 10 mu m miming the typical size of a red blood cell and so, supporting free circulation in human tissues. Moreover, an ultra-low-power architecture is needed since the system is battery-less and wirelessly powered via acoustic power transfer. The aim of this paper is to present a data communication system for Body Dust systems, which works from the multiplexed sensor read-out front-end to the transmitter back-end taking account diagnostic information on different metabolite concentrations in human body. This work shows that scaling the architecture from a 0.18-mu m to 28-nm CMOS processes, it is possible to improve both size and power consumption. The improvement is about 40 times in size (2000 mu m(2) down to 50 mu m2) and two order of magnitude in average power consumption (10 mu W to cents of nW).

Miniaturised Wireless Power Transfer Systems for Neurostimulation: A Review

G. L. Barbruni; P. Motto Ros; D. Demarchi; S. Carrara; D. Ghezzi

In neurostimulation, wireless power transfer is an efficient technology to overcome several limitations affecting medical devices currently used in clinical practice. Several methods were developed over the years for wireless power transfer. In this review article, we report and discuss the three most relevant methodologies for extremely miniaturised implantable neurostimulator: ultrasound coupling, inductive coupling and capacitive coupling. For each powering method, the discussion starts describing the physical working principle. In particular, we focus on the challenges given by the miniaturisation of the implanted integrated circuits and the related ad-hoc solutions for wireless power transfer. Then, we present recent developments and progresses in wireless power transfer for biomedical applications. Last, we compare each technique based on key performance indicators to highlight the most relevant and innovative solutions suitable for neurostimulation, with the gaze turned towards miniaturisation.

DOI : 10.1109/TBCAS.2020.3038599