Advances in Microelectronics for Implantable Medical Devices

Implantable medical devices provide therapy to treat numerous health conditions as well as monitoring and diagnosis. Over the years, the development of these devices has seen remarkable progress thanks to tremendous advances in microelectronics, electrode technology, packaging and signal processing techniques. Many of today’s implantable devices use wireless technology to supply power and provide communication. There are many challenges when creating an implantable device. Issues such as reliable and fast bidirectional data communication, efficient power delivery to the implantable circuits, low noise and low power for the recording part of the system, and delivery of safe stimulation to avoid tissue and electrode damage are some of the challenges faced by the microelectronics circuit designer. This paper provides a review of advances in microelectronics over the last decade or so for implantable medical devices and systems. The focus is on neural recording and stimulation circuits suitable for fabrication in modern silicon process technologies and biotelemetry methods for power and data transfer, with particular emphasis on methods employing radio frequency inductive coupling. The paper concludes by highlighting some of the issues that will drive future research in the field

A Multi-Channel Low-Power System-on-Chip for in vivo NeuralSpike Recording

This paper reports a multi-channel neural spike recording system-on-chip (SoC) with digital data compression and wireless telemetry. The circuit consists of a 64-channel low-power low-noise analog front-end, a single 8-bit analog-todigital converter (ADC), followed by digital signal compression and transmission units. The 400-MHz transmitter employs a Manchester-Coded Frequency Shift Keying (MC-FSK) modulator with low modulation index. In this way a 1.25-Mbit/s data rate is delivered within a band of about 3 MHz. Compression of the raw data is implemented by detecting the action potentials (APs) and storing 20 samples for each spike waveform. The choice greatly improves data quality and allows single neuron identification. A larger than 10-m transmission range is reached with an overall power consumption of 17.2 mW. This figure translates into a power budget of 269 μW per channel, which is in line with the results in literature but allowing a larger transmission distance and more efficient wireless link bandwidth occupation. The implemented IC was mounted on a small and light printed circuit board to be used during neuroscience experiments with freely-behaving rats. Powered by 2 AAA batteries the system can work continuously for more than 100 hours allowing long-lasting neural spike recordings

Algorithm and Hardware Co-Design for Local/Edge Computing

Advances in VLSI manufacturing and design technology over the decades have created many computing paradigms for disparate computing needs. With concerns for transmission cost, security, latency of centralized computing, edge/local computing are increasingly prevalent in the faster growing sectors like Internet-of-Things (IoT) and other sectors that require energy/connectivity autonomous systems such as biomedical and industrial applications. Energy and power efficient are the main design constraints in local and edge computing. While there exists a wide range of low power design techniques, they are often underutilized in custom circuit designs as the algorithms are developed independent of the hardware. Such compartmentalized design approach fails to take advantage of the many compatible algorithmic and hardware techniques that can improve the efficiency of the entire system. Algorithm hardware co-design is to explore the design space with whole stack awareness. The main goal of the algorithm hardware co-design methodology is the enablement and improvement of small form factor edge and local VLSI systems operating under strict constraints of area and energy efficiency. This thesis presents selected works of application specific digital and mixed-signal integrated circuit designs. The application space ranges from implantable biomedical devices to edge machine learning acceleration

Acquisition systems and decoding algorithms of peripheral neural signals for prosthetic applications

During the years, neuroprosthetic applications have obtained a great deal of attention by the international research, especially in the bioengineering field, thanks to the huge investments on several proposed projects funded by the political institutions which consider the treatment of this particular disease of fundamental importance for the global community. The aim of these projects is to find a possible solution to restore the functionalities lost by a patient subjected to an upper limb amputation trying to develop, according to physiological considerations, a communication link between the brain in which the significant signals are generated and a motor prosthesis device able to perform the desired action. Moreover, the designed system must be able to give back to the brain a sensory feedback about the surrounding world in terms of pressure or temperature acquired by tactile biosensors placed at the surface of the cybernetic hand. It in fact allows to execute involuntarymovements when for example the armcomes in contact with hot objects. The development of such a closed-loop architecture involves the need to address some critical issues which depend on the chosen approach. Several solutions have been proposed by the researches of the field, each one differing with respect to where the neural signals are acquired, either at the central nervous systemor at the peripheral one,most of themfollowing the former even that the latter is always considered by the amputees amore natural way to handle the artificial limb. This research work is based on the use of intrafascicular electrodes directly implanted in the residual peripheral nerves of the stump which represents a good compromise choice in terms of invasiveness and selectivity extracting electroneurographic (ENG) signals from which it is possible to identify the significant activity of a quite limited number of neuronal cells. In the perspective of the hardware implementation of the resulting solution which can work autonomously without any intervention by the amputee in an adaptive way according to the current characteristics of the processed signal and by using batteries as power source allowing portability, it is necessary to fulfill the tight constraints imposed by the application under consideration involved in each of the various phases which compose the considered closed-loop system. Regarding to the recording phase, the implementation must be able to remove the unwanted interferences mainly due to the electro-stimulations of themuscles placed near the electrodes featured by an order of magnitude much greater in comparison to that of the signals of interest amplifying the frequency components belonging to the significant bandwidth, and to convert them with a high resolution in order to obtain good performance at the next processing phases. To this aim, a recording module for peripheral neural signals will be presented, based on the use of a sigma-delta architecture which is composed by two main parts: an analog front-end stage for neural signal acquisition, pre-filtering and sigma-delta modulation and a digital unit for sigma-delta decimation and system configuration. Hardware/software cosimulations exploiting the Xilinx System Generator tool in Matlab Simulink environment and then transistor-level simulations confirmed that the system is capable of recording neural signals in the order of magnitude of tens of μV rejecting the huge low-frequency noise due to electromyographic interferences. The same architecture has been then exploited to implement a prototype of an 8-channel implantable electronic bi-directional interface between the peripheral nervous system and the neuro-controlled hand prosthesis. The solution includes a custom designed Integrated Circuit (0.35μm CMOS technology), responsible of the signal pre-filtering and sigma-delta modulation for each channel and the neural stimuli generation (in the opposite path) based on the directives sent by a digital control systemmapped on a low-cost Xilinx FPGA Spartan-3E 1600 development board which also involves the multi-channel sigma-delta decimation with a high-order band-pass filter as first stage in order to totally remove the unwanted interferences. In this way, the analog chip can be implanted near the electrodes thanks to its limited size avoiding to add a huge noise to theweak neural signals due to longwires connections and to cause heat-related infections, shifting the complexity to the digital part which can be hosted on a separated device in the stump of the amputeewithout using complex laboratory instrumentations. The system has been successfully tested from the electrical point of view and with in-vivo experiments exposing good results in terms of output resolution and noise rejection even in case of critical conditions. The various output channels at the Nyquist sampling frequency coming from the acquisition system must be processed in order to decode the intentions of movements of the amputee, applying the correspondent electro-mechanical stimulation in input to the cybernetic hand in order to perform the desired motor action. Different decoding approaches have been presented in the past, the majority of them were conceived starting from the relative implementation and performance evaluation of their off-line version. At the end of the research, it is necessary to develop these solutions on embedded systems performing an online processing of the peripheral neural signals. However, it is often possible only by using complex hardware platforms clocked at very high operating frequencies which are not be compliant with the low-power requirements needed to allow portability for the prosthetic device. At present, in fact, the important aspect of the real-time implementation of sophisticated signal processing algorithms on embedded systems has been often overlooked, notwithstanding the impact that limited resources of the former may have on the efficiency/effectiveness of any given algorithm. In this research work it has been addressed the optimization of a state-of-the-art algorithmfor PNS signals decoding that is a step forward for its real-time, full implementation onto a floating-point Digital Signal Processor (DSP). Beyond low-level optimizations, different solutions have been proposed at an high level in order to find the best trade-off in terms of effectiveness/efficiency. A latency model, obtained through cycle accurate profiling of the different code sections, has been drawn in order to perform a fair performance assessment. The proposed optimized real-time algorithmachieves up to 96% of correct classification on real PNS signals acquired through tf-LIFE electrodes on animals, and performs as the best off-line algorithmfor spike clustering on a synthetic cortical dataset characterized by a reasonable dissimilarity between the spikemorphologies of different neurons. When the real-time requirements are joined to the fulfilment of area and power minimization for implantable/portable applications, such as for the target neuroprosthetic devices, only custom VLSI implementations can be adopted. In this case, every part of the algorithmshould be carefully tuned. To this aim, the first preprocessing stage of the decoding algorithmbased on the use of aWavelet Denoising solution able to remove also the in-band noise sources has been deeply analysed in order to obtain an optimal hardware implementation. In particular, the usually overlooked part related to threshold estimation has been evaluated in terms of required hardware resources and functionality, exploiting the commercial Xilinx System Generator tool for the design of the architecture and the co-simulation. The analysis has revealed how the widely used Median Absolute Deviation (MAD) could lead o hardware implementations highly inefficient compared to other dispersion estimators demonstrating better scalability, relatively to the specific application. Finally, two different hardware implementations of the reference decoding algorithm have been presented highlighting pros and cons of each one of them. Firstly, a novel approach based on high-level dataflow description and automatic hardware generation is presented and evaluated on the on-line template-matching spike sorting algorithmwhich represents the most complex processing stage. It starts from the identification of the single kernels with the greater computational complexity and using their dataflow description to generate the HDL implementation of a coarse-grained reconfigurable global kernel characterized by theminimumresources in order to reduce the area and the energy dissipation for the fulfilment of the low-power requirements imposed by the application. Results in the best case have revealed a 71%of area saving compared tomore traditional solutions,without any accuracy penalty. With respect to single kernels execution, better latency performance are achievable stillminimizing the number of adopted resources. The performance in terms of latency can also be improved by tuning the implemented parallelismin the light of a defined number of channels and real-time constraints, by using more than one reconfigurable global kernel in order that they can be exploited to perform the same or different kernels at the same time in a parallel way, due to the fact that each one can execute the relative processing only in a sequential way. For this reason, a second FPGA-based prototype has been proposed based on the use of aMulti-Processor System-on-Chip (MPSoC) embedded architecture. This prototype is capable of respecting the real-time constraints posed by the application when clocked at less than 50 MHz, in comparison to 300 MHz of the previous DSP implementation. Considering that the application workload is extremely data dependent and unpredictable due to the sparsity of the neural signals, the architecture has to be dimensioned taking into account critical worst-case operating conditions in order to always ensure the correct functionality. To compensate the resulting overprovisioning of the system architecture, a software-controllable power management based on the use of clock gating techniques has been integrated in order tominimize the dynamic power consumption of the resulting solution. Summarizing, this research work can be considered a sort of proof-of-concept for the proposed techniques considering all the design issues which characterize each stage of the closed-loop system in the perspective of a portable low-power real-time hardware implementation of the neuro-controlled prosthetic device

Acquisition systems and decoding algorithms of peripheral neural signals for prosthetic applications

During the years, neuroprosthetic applications have obtained a great deal of attention by the international research, especially in the bioengineering field, thanks to the huge investments on several proposed projects funded by the political institutions which consider the treatment of this particular disease of fundamental importance for the global community. The aim of these projects is to find a possible solution to restore the functionalities lost by a patient subjected to an upper limb amputation trying to develop, according to physiological considerations, a communication link between the brain in which the significant signals are generated and a motor prosthesis device able to perform the desired action. Moreover, the designed system must be able to give back to the brain a sensory feedback about the surrounding world in terms of pressure or temperature acquired by tactile biosensors placed at the surface of the cybernetic hand. It in fact allows to execute involuntarymovements when for example the armcomes in contact with hot objects. The development of such a closed-loop architecture involves the need to address some critical issues which depend on the chosen approach. Several solutions have been proposed by the researches of the field, each one differing with respect to where the neural signals are acquired, either at the central nervous systemor at the peripheral one,most of themfollowing the former even that the latter is always considered by the amputees amore natural way to handle the artificial limb. This research work is based on the use of intrafascicular electrodes directly implanted in the residual peripheral nerves of the stump which represents a good compromise choice in terms of invasiveness and selectivity extracting electroneurographic (ENG) signals from which it is possible to identify the significant activity of a quite limited number of neuronal cells. In the perspective of the hardware implementation of the resulting solution which can work autonomously without any intervention by the amputee in an adaptive way according to the current characteristics of the processed signal and by using batteries as power source allowing portability, it is necessary to fulfill the tight constraints imposed by the application under consideration involved in each of the various phases which compose the considered closed-loop system. Regarding to the recording phase, the implementation must be able to remove the unwanted interferences mainly due to the electro-stimulations of themuscles placed near the electrodes featured by an order of magnitude much greater in comparison to that of the signals of interest amplifying the frequency components belonging to the significant bandwidth, and to convert them with a high resolution in order to obtain good performance at the next processing phases. To this aim, a recording module for peripheral neural signals will be presented, based on the use of a sigma-delta architecture which is composed by two main parts: an analog front-end stage for neural signal acquisition, pre-filtering and sigma-delta modulation and a digital unit for sigma-delta decimation and system configuration. Hardware/software cosimulations exploiting the Xilinx System Generator tool in Matlab Simulink environment and then transistor-level simulations confirmed that the system is capable of recording neural signals in the order of magnitude of tens of μV rejecting the huge low-frequency noise due to electromyographic interferences. The same architecture has been then exploited to implement a prototype of an 8-channel implantable electronic bi-directional interface between the peripheral nervous system and the neuro-controlled hand prosthesis. The solution includes a custom designed Integrated Circuit (0.35μm CMOS technology), responsible of the signal pre-filtering and sigma-delta modulation for each channel and the neural stimuli generation (in the opposite path) based on the directives sent by a digital control systemmapped on a low-cost Xilinx FPGA Spartan-3E 1600 development board which also involves the multi-channel sigma-delta decimation with a high-order band-pass filter as first stage in order to totally remove the unwanted interferences. In this way, the analog chip can be implanted near the electrodes thanks to its limited size avoiding to add a huge noise to theweak neural signals due to longwires connections and to cause heat-related infections, shifting the complexity to the digital part which can be hosted on a separated device in the stump of the amputeewithout using complex laboratory instrumentations. The system has been successfully tested from the electrical point of view and with in-vivo experiments exposing good results in terms of output resolution and noise rejection even in case of critical conditions. The various output channels at the Nyquist sampling frequency coming from the acquisition system must be processed in order to decode the intentions of movements of the amputee, applying the correspondent electro-mechanical stimulation in input to the cybernetic hand in order to perform the desired motor action. Different decoding approaches have been presented in the past, the majority of them were conceived starting from the relative implementation and performance evaluation of their off-line version. At the end of the research, it is necessary to develop these solutions on embedded systems performing an online processing of the peripheral neural signals. However, it is often possible only by using complex hardware platforms clocked at very high operating frequencies which are not be compliant with the low-power requirements needed to allow portability for the prosthetic device. At present, in fact, the important aspect of the real-time implementation of sophisticated signal processing algorithms on embedded systems has been often overlooked, notwithstanding the impact that limited resources of the former may have on the efficiency/effectiveness of any given algorithm. In this research work it has been addressed the optimization of a state-of-the-art algorithmfor PNS signals decoding that is a step forward for its real-time, full implementation onto a floating-point Digital Signal Processor (DSP). Beyond low-level optimizations, different solutions have been proposed at an high level in order to find the best trade-off in terms of effectiveness/efficiency. A latency model, obtained through cycle accurate profiling of the different code sections, has been drawn in order to perform a fair performance assessment. The proposed optimized real-time algorithmachieves up to 96% of correct classification on real PNS signals acquired through tf-LIFE electrodes on animals, and performs as the best off-line algorithmfor spike clustering on a synthetic cortical dataset characterized by a reasonable dissimilarity between the spikemorphologies of different neurons. When the real-time requirements are joined to the fulfilment of area and power minimization for implantable/portable applications, such as for the target neuroprosthetic devices, only custom VLSI implementations can be adopted. In this case, every part of the algorithmshould be carefully tuned. To this aim, the first preprocessing stage of the decoding algorithmbased on the use of aWavelet Denoising solution able to remove also the in-band noise sources has been deeply analysed in order to obtain an optimal hardware implementation. In particular, the usually overlooked part related to threshold estimation has been evaluated in terms of required hardware resources and functionality, exploiting the commercial Xilinx System Generator tool for the design of the architecture and the co-simulation. The analysis has revealed how the widely used Median Absolute Deviation (MAD) could lead o hardware implementations highly inefficient compared to other dispersion estimators demonstrating better scalability, relatively to the specific application. Finally, two different hardware implementations of the reference decoding algorithm have been presented highlighting pros and cons of each one of them. Firstly, a novel approach based on high-level dataflow description and automatic hardware generation is presented and evaluated on the on-line template-matching spike sorting algorithmwhich represents the most complex processing stage. It starts from the identification of the single kernels with the greater computational complexity and using their dataflow description to generate the HDL implementation of a coarse-grained reconfigurable global kernel characterized by theminimumresources in order to reduce the area and the energy dissipation for the fulfilment of the low-power requirements imposed by the application. Results in the best case have revealed a 71%of area saving compared tomore traditional solutions,without any accuracy penalty. With respect to single kernels execution, better latency performance are achievable stillminimizing the number of adopted resources. The performance in terms of latency can also be improved by tuning the implemented parallelismin the light of a defined number of channels and real-time constraints, by using more than one reconfigurable global kernel in order that they can be exploited to perform the same or different kernels at the same time in a parallel way, due to the fact that each one can execute the relative processing only in a sequential way. For this reason, a second FPGA-based prototype has been proposed based on the use of aMulti-Processor System-on-Chip (MPSoC) embedded architecture. This prototype is capable of respecting the real-time constraints posed by the application when clocked at less than 50 MHz, in comparison to 300 MHz of the previous DSP implementation. Considering that the application workload is extremely data dependent and unpredictable due to the sparsity of the neural signals, the architecture has to be dimensioned taking into account critical worst-case operating conditions in order to always ensure the correct functionality. To compensate the resulting overprovisioning of the system architecture, a software-controllable power management based on the use of clock gating techniques has been integrated in order tominimize the dynamic power consumption of the resulting solution. Summarizing, this research work can be considered a sort of proof-of-concept for the proposed techniques considering all the design issues which characterize each stage of the closed-loop system in the perspective of a portable low-power real-time hardware implementation of the neuro-controlled prosthetic device

A Multi-Channel Low-Power System-on-Chip for in Vivo Recording and Wireless Transmission of Neural Spikes

This paper reports a multi-channel neural spike recording system-on-chip with digital data compression and wireless telemetry. The circuit consists of 16 amplifiers, an analog time-division multiplexer, a single 8 bit analog-to-digital converter, a digital signal compression unit and a wireless transmitter. Although only 16 amplifiers are integrated in our current die version, the whole system is designed to work with 64, demonstrating the feasibility of a digital processing and narrowband wireless transmission of 64 neural recording channels. Compression of the raw data is achieved by detecting the action potentials (APs) and storing 20 samples for each spike waveform. This compression method retains sufficiently high data quality to allow for single neuron identification (spike sorting). The 400 MHz transmitter employs a Manchester-Coded Frequency Shift Keying (MC-FSK) modulator with low modulation index. In this way, a 1.25 Mbit/s data rate is delivered within a limited band of about 3 MHz. The chip is realized in a 0.35 um AMS CMOS process featuring a 3 V power supply with an area of 3.1x 2.7 mm2. The achieved transmission range is over 10 m with an overall power consumption for 64 channels of 17.2 mW. This figure translates into a power budget of 269uW per channel, in line with published results but allowing a larger transmission distance and more efficient bandwidth occupation of the wireless link. The integrated circuit was mounted on a small and light board to be used during neuroscience experiments with freely-behaving rats. Powered by 2 AAA batteries, the system can continuously work for more than 100 hours allowing for long-lasting neural spike recordings

Recent Advances in Neural Recording Microsystems

The accelerating pace of research in neuroscience has created a considerable demand for neural interfacing microsystems capable of monitoring the activity of large groups of neurons. These emerging tools have revealed a tremendous potential for the advancement of knowledge in brain research and for the development of useful clinical applications. They can extract the relevant control signals directly from the brain enabling individuals with severe disabilities to communicate their intentions to other devices, like computers or various prostheses. Such microsystems are self-contained devices composed of a neural probe attached with an integrated circuit for extracting neural signals from multiple channels, and transferring the data outside the body. The greatest challenge facing development of such emerging devices into viable clinical systems involves addressing their small form factor and low-power consumption constraints, while providing superior resolution. In this paper, we survey the recent progress in the design and the implementation of multi-channel neural recording Microsystems, with particular emphasis on the design of recording and telemetry electronics. An overview of the numerous neural signal modalities is given and the existing microsystem topologies are covered. We present energy-efficient sensory circuits to retrieve weak signals from neural probes and we compare them. We cover data management and smart power scheduling approaches, and we review advances in low-power telemetry. Finally, we conclude by summarizing the remaining challenges and by highlighting the emerging trends in the field

Closed-loop approaches for innovative neuroprostheses

The goal of this thesis is to study new ways to interact with the nervous system in case of damage or pathology. In particular, I focused my effort towards the development of innovative, closed-loop stimulation protocols in various scenarios: in vitro, ex vivo, in vivo