Implantable Autonomous Wireless Closed-loop Bio-electronics for Epilepsy Control

Implantable electronic medical device (IEMD) is an emerging technology that plays an important role in the treatment of several neurological disorders such as epilepsy, especially in the cases of drug-resistant epilepsy. Recent developments and studies show the possibility of accurate detection of seizure onset and stopping the seizures or shortening their duration using electrical neural stimulation. By employing these devices, the quality of the life of the patients who could not benefit from anti-epileptic medicines or surgery will improve, significantly. An IEMD uses a neural recording interface to sense and amplify neural signals. Increasing the number of recording channels from few recording channels to hundreds is a promising feature of the future IEMDs. However, employing hundreds of recording channels brings several challenges including minimizing the power consumption which relates to the temperature elevation in the device and may damage the tissues around the IEMD. In order to implement a low-power implantable electronic device for neural recording, epilepsy detection and epilepsy control with a high spatiotemporal resolution, some techniques should be devised to solve this issue.

Closed-loop implantable electronics is a new trend for controlling seizures by detecting them and applying an electrical stimulation to the brain or a group of nerves. These devices employ electrical stimulators; however, electrical stimulation requires very careful consideration due to the safety issues. A poor design of the electrical stimulator may damage the brain tissue and endanger the life of the patients. Hence, charge balancers are introduced to ensure the safety of the electrical stimulation. In addition, closed-loop implantable devices for seizure control require an accurate seizure onset detector. These devices should detects all the seizures with the least latency to stop the seizures or stop them to spread in the brain.

The first part of this thesis presents a low-power and compact size seizure detection system while discussing the challenges in the design of neural amplifiesr, feature extractors and data compression circuits. Then a comprehensive study on electrical stimulation and charge balancing are provided. Consequently, circuit techniques to achieve a low-power, low-are and accurate charge balancers are present. Finally, a neural recording system based on orthogonal sampling and two closed-loop stimulation systems for epilepsy control are proposed. Orthogonal sampling enables reducing the number of the ADCs in conventional recording systems into one single unit while simultaneously recording from several channels. Consequently, the ADC bandwidth and dynamic range is effectively employed and shared between all the channels without any loss in the temporal information of the channels during sampling, which is not the case of time-multiplexed ADCs. In an IoT based closed-loop stimulation system for epilepsy control, the system is divided into two parts including implantable part and external parts. Using wearable devices, several biomarkers are recorded and sent to the implantable part of the system to improve the accuracy of the detection. In the end, an all wireless implantable closed-loop stimulation system is presented with an accurate charge balanced stimulator.

Low-Power Circuit and System Design for Epileptic Seizure Detection at High Spatiotemporal Resolution

Mahsa Shoaran

Smart and miniaturized implantable microsystems with diagnostic and therapeutic capabilities are becoming increasingly important for patients suffering from neurological disorders such as epilepsy. Recent developments in microfabrication technology have provided new insights into seizure generation at an unprecedented spatial scale. Based on these findings, designing powerful acquisition systems capable of probing the wide-range spatiotemporal activities within the brain holds a great promise to improve the quality of life of epileptic patients. It is expected that future neural recording interfaces will integrate hundreds of acquisition channels at relatively high sampling rates, making it crucial to perform sophisticated signal conditioning tasks within the sensors. A small size of the implantable system is critical to minimize potential clinical issues associated with implantation. The total power consumption should be minimized to avoid heat generation inside the brain. Substantial improvements in neural implant safety and longevity are needed to translate existing multisite neural recording systems into technology suitable for long-term use in patients. As a major technological barrier, the high overall data rates of digitized neural signals collected by dense electrode arrays can drastically increase the power consumption of the wireless transmission module. Consequently, extensive system-level design improvement is needed to meet the requirements of the implantable device, while preserving the high-resolution monitoring capability. In this context, we target the exploration and development of novel methods and tools for more accurate monitoring of the electrical activity of the epileptic brain during seizures. A precise focus localization and accurate early seizure detection are two major goals. Low-power circuit and system design techniques for data acquisition, compression and seizure detection in multichannel cortical implants are presented. In this context, the first fully-integrated circuit that addresses the multichannel compressed-domain feature extraction is proposed. Circuit challenges and techniques to optimize the neural amplifier topology at the frontend of the signal acquisition chain, in terms of power consumption, die area and noise are discussed. Then, compressive sensing is utilized as the main data reduction method in the proposed system. The existing microelectronic implementations of compressive sensing are applied in a single-channel basis. Therefore, these topologies incur a high power consumption and large silicon area. To overcome these issues, a new multichannel measurement scheme and an appropriate recovery scheme are proposed, which encode the whole array into a single compressed data stream. This technique circumvents the need to place one analog-to-digital converter inside each channel, which results in a significant area saving. Taking benefit of the area-efficient implementation of compressive sensing, the number of recording units implantable on the cortex which satisfy the energy constraints of the system is scaled up by a factor equal to the compression ratio. Finally, a new feature extraction method applied on the compressed signal of several channels is proposed. The spatial evolution of the intracranial EEG signals recorded by the adjacent electrodes and the corresponding behaviour in the compressed domain are exploited for detecting seizure onset.

EPFL2015

A Microfluidic Brain Interface for In Vivo Recording of Neurochemical Activity

Guillaume Cédric Yves Petitpierre

Neurological disorders have a strong negative impact on the quality of life of affected patients, their close relatives as well as on the health economic system. Early diagnosis associated with better treatment outcomes remain difficult to reach. Similarly, misdiagnosis is frequent and can lead to the delivery of the wrong treatment to the patient. As a matter of fact, the therapeutic strategies developed to treat Alzheimer's Disease (AD) and Parkinson's Disease (PD), two major neurodegenerative diseases, are unfortunately only effective for reducing the symptoms. This illustrates the lack of complete understanding of the mechanisms underlining neurodegeneration. In this context, this thesis aims to contribute to a precise comprehension of the synaptic transmission, at the cellular level, by providing a biocompatible brain interface capable of collecting neurochemicals while establishing a tight electrical connection with the cerebral tissues. The first part of this thesis deals with the design and microfabrication of a novel neural probe which includes microelectrodes and a micro-scale droplet generator for the efficient collection of extracellular fluid. The design choices and the microfabrication approach are detailed while the behavior of the device is assessed using fluidic modeling. Experimental results regarding the neural probe's mechanical strength, electrical and fluidic functions are then presented. In particular, the electrode-tissue interface is assessed using impedance spectroscopy. The probe fluidic function and its ability to perform high frequency (6Hz) droplet segmented collection in a rapidly changing environment is experimentally demonstrated. In a second phase is reported the successful in vivo testing of the neural probe in the framework of a pilot animal trial performed on rats. A custom microfabricated analysis platform enabling to efficiently detect the content of the collected brain fluid samples is presented as well. In particular a microfabricated target plate for the distribution and handling of the segmented samples during analysis is reported. This unique approach allows to maintain the temporal history of the flow-segmented samples. Combined with Inductively Coupled (ICP) Mass Spectrometry (MS), the detection results show the presence in significant quantity of Na, Mg, K and Ca, reflecting the neurochemical state of the brain over time. Quantitative measurements are demonstrated, highlighting the power of this approach. Simultaneous cerebral tissues electrical modulation and neurochemical recording during periods of 15 min is demonstrated in a third phase. A significant neurochemical response is detected in correlation with the electrical stimulation periods (2 x 1 min). In particular, the extracellular K+ ion concentration appears to rise during these periods which is further confirmed on each of the 3 implanted subjects. It is stated that the electrical stimulation delivered to the tissues set the neurons in a permanent hyperpolarized state, forcing a strong K+ ions efflux towards the extracellular space. This work sets a basis for the development of novel approaches in the detection of malfunction in synaptic transmission. Future perspectives of this technology include new methods enabling earlier diagnosis of neurodegenerative diseases and more efficient treatments based on a closed-loop adjustment of electrical stimulation.

EPFL2017

Development of a Transient Neural Interface for Minimally Invasive Recording and Stimulation

Adele Fanelli

Transient electronics enabling devices to safely disappear in the environment can be applied not only in green electronics, but also in bioelectronic medicine. Neural implants able to degrade harmlessly inside the body eliminate the need for removal surgery, allow for safe tissue remodelling, and potentially reduce inflammation responses and the chronic adverse reactions hindering device functionality and putting patients' health at risk. Sadly, current transient neurotechnology can be used only for very short-term applications. Fast degrading metals generally used to build these interfaces allow in fact for operations rarely longer than a few days, strongly limiting the available time window for collecting information or for a therapy to be finished.To solve this problem, we propose a transient, all-polymeric neural interface able to work for longer time scales. This would enable new applications of transient neurotechnology, such as recording of brain activity for a prolonged and more useful period of time before resection of epilepsy foci or tumours. The device consists of a polycaprolactone (PCL) scaffold with patterned poly 3,4-ethylene dioxythiophene : polystyrene sulfonate (PEDOT:PSS) traces and electrodes. In vivo neural recording demonstrated low noise levels for twelve weeks and histological analysis highlighted the cellular infiltration inside the PCL scaffold over time, hinting to potential tissue remodelling processes, which would not occur with a non-degradable device. To increase the device potential for a clinical translation, a minimally invasive procedure for its implantation has been proposed. The blood vasculature supplying the brain and nerves can be used as an access route to the neural tissue, offering a close enough location without direct damage to the tissue. By re-shaping the all-polymeric transient neural probe using a stent-inspired design, the new interface can be navigated through a 5Fr catheter and deployed inside 2 mm-diameter channels. Characterization showed promising electrodes endurance to pulsatile flow and prolonged stimulation, together with a good safety profile. This device can be used for neural recording or stimulation from within a blood vessel, for either central or peripheral nervous system. By simplifying the implantation procedure of the neural interface and maintaining its transiency, physicians and patients could feel more confident in applying innovative neurotechnology-based treatments, widening for example the access to deep brain stimulation therapy. To enable crossing of complex vasculature without wall ruptures caused by current manual push of guidewires, a new navigation paradigm for endovascular devices has been designed and tested on thin polyimide strips. A physiological pulsatile flow can propel these probes, even at curvatures as high as 0.25 mm-1, and low amplitude magnetic fields can steer their direction. Electrodes and sensors for temperature and flow can be embedded onto these micro-probes, for unprecedented local interrogation of deep vasculature regions. In conclusion, this thesis introduces new neural interfaces in the field of minimally invasive neurotechnology, reducing adverse effects and complications of non-degradable implants and open surgery. These devices and their concepts have the potential one day to be new tools of the bioelectronic medicine toolbox, contributing to the advancement of innovative treatments for neurodegenerative disorders.

EPFL2022