Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes

Extracellular electrode arrays can reveal the neuronal network correlates of behavior with single-cell, single-spike, and sub-millisecond resolution. However, implantable electrodes are inherently invasive, and efforts to scale up the number and density of recording sites must compromise on device size in order to connect the electrodes. Here, we report on silicon-based neural probes employing nanofabricated, high-density electrical leads. Furthermore, we address the challenge of reading out multichannel data with an application-specific integrated circuit (ASIC) performing signal amplification, band-pass filtering, and multiplexing functions. We demonstrate high spatial resolution extracellular measurements with a fully integrated, low noise 64-channel system weighing just 330 mg. The on-chip multiplexers make possible recordings with substantially fewer external wires than the number of input channels. By combining nanofabricated probes with ASICs we have implemented a system for performing large-scale, high-density electrophysiology in small, freely behaving animals that is both minimally invasive and highly scalable

Neonatal seizure detection based on single-channel EEG: instrumentation and algorithms

Seizure activity in the perinatal period, which constitutes the most common neurological emergency in the neonate, can cause brain disorders later in life or even death depending on their severity. This issue remains unsolved to date, despite the several attempts in tackling it using numerous methods. Therefore, a method is still needed that can enable neonatal cerebral activity monitoring to identify those at risk. Currently, electroencephalography (EEG) and amplitude-integrated EEG (aEEG) have been exploited for the identification of seizures in neonates, however both lack automation. EEG and aEEG are mainly visually analysed, requiring a specific skill set and as a result the presence of an expert on a 24/7 basis, which is not feasible. Additionally, EEG devices employed in neonatal intensive care units (NICU) are mainly designed around adults, meaning that their design specifications are not neonate specific, including their size due to multi-channel requirement in adults - adults minimum requirement is ≥ 32 channels, while gold standard in neonatal is equal to 10; they are bulky and occupy significant space in NICU. This thesis addresses the challenge of reliably, efficiently and effectively detecting seizures in the neonatal brain in a fully automated manner. Two novel instruments and two novel neonatal seizure detection algorithms (SDAs) are presented. The first instrument, named PANACEA, is a high-performance, wireless, wearable and portable multi-instrument, able to record neonatal EEG, as well as a plethora of (bio)signals. This device despite its high-performance characteristics and ability to record EEG, is mostly suggested to be used for the concurrent monitoring of other vital biosignals, such as electrocardiogram (ECG) and respiration, which provide vital information about a neonate's medical condition. The two aforementioned biosignals constitute two of the most important artefacts in the EEG and their concurrent acquisition benefit the SDA by providing information to an artefact removal algorithm. The second instrument, called neoEEG Board, is an ultra-low noise, wireless, portable and high precision neonatal EEG recording instrument. It is able to detect and record minute signals (< 10 nVp) enabling cerebral activity monitoring even from lower layers in the cortex. The neoEEG Board accommodates 8 inputs each one equipped with a patent-pending tunable filter topology, which allows passband formation based on the application. Both the PANACEA and the neoEEG Board are able to host low- to middle-complexity SDAs and they can operate continuously for at least 8 hours on 3-AA batteries. Along with PANACEA and the neoEEG Board, two novel neonatal SDAs have been developed. The first one, termed G prime-smoothed (G ́_s), is an on-line, automated, patient-specific, single-feature and single-channel EEG based SDA. The G ́_s SDA, is enabled by the invention of a novel feature, termed G prime (G ́) and can be characterised as an energy operator. The trace that the G ́_s creates, can also be used as a visualisation tool because of its distinct change at a presence of a seizure. Finally, the second SDA is machine learning (ML)-based and uses numerous features and a support vector machine (SVM) classifier. It can be characterised as automated, on-line and patient-independent, and similarly to G ́_s it makes use of a single-channel EEG. The proposed neonatal SDA introduces the use of the Hilbert-Huang transforms (HHT) in the field of neonatal seizure detection. The HHT analyses the non-linear and non-stationary EEG signal providing information for the signal as it evolves. Through the use of HHT novel features, such as the per intrinsic mode function (IMF) (0-3 Hz) sub-band power, were also employed. Detection rates of this novel neonatal SDA is comparable to multi-channel SDAs.Open Acces

A high-performance 8 nV/root Hz 8-channel wearable and wireless system for real-time monitoring of bioelectrical signals

Background: It is widely accepted by the scientific community that bioelectrical signals, which can be used for the identification of neurophysiological biomarkers indicative of a diseased or pathological state, could direct patient treatment towards more effective therapeutic strategies. However, the design and realisation of an instrument that can precisely record weak bioelectrical signals in the presence of strong interference stemming from a noisy clinical environment is one of the most difficult challenges associated with the strategy of monitoring bioelectrical signals for diagnostic purposes. Moreover, since patients often have to cope with the problem of limited mobility being connected to bulky and mains-powered instruments, there is a growing demand for small-sized, high-performance and ambulatory biopotential acquisition systems in the Intensive Care Unit (ICU) and in High-dependency wards. Finally, to the best of our knowledge, there are no commercial, small, battery-powered, wearable and wireless recording-only instruments that claim the capability of recording electrocorticographic (ECoG) signals. Methods: To address this problem, we designed and developed a low-noise (8 nV/√Hz), eight-channel, battery-powered, wearable and wireless instrument (55 × 80 mm2). The performance of the realised instrument was assessed by conducting both ex vivo and in vivo experiments. Results: To provide ex vivo proof-of-function, a wide variety of high-quality bioelectrical signal recordings are reported, including electroencephalographic (EEG), electromyographic (EMG), electrocardiographic (ECG), acceleration signals, and muscle fasciculations. Low-noise in vivo recordings of weak local field potentials (LFPs), which were wirelessly acquired in real time using segmented deep brain stimulation (DBS) electrodes implanted in the thalamus of a non-human primate, are also presented. Conclusions: The combination of desirable features and capabilities of this instrument, namely its small size (~one business card), its enhanced recording capabilities, its increased processing capabilities, its manufacturability (since it was designed using discrete off-the-shelf components), the wide bandwidth it offers (0.5 – 500 Hz) and the plurality of bioelectrical signals it can precisely record, render it a versatile and reliable tool to be utilized in a wide range of applications and environments

Wired, wireless and wearable bioinstrumentation for high-precision recording of bioelectrical signals in bidirectional neural interfaces

It is widely accepted by the scientific community that bioelectrical signals, which can be used for the identification of neurophysiological biomarkers indicative of a diseased or pathological state, could direct patient treatment towards more effective therapeutic strategies. However, the design and realisation of an instrument that can precisely record weak bioelectrical signals in the presence of strong interference stemming from a noisy clinical environment is one of the most difficult challenges associated with the strategy of monitoring bioelectrical signals for diagnostic purposes. Moreover, since patients often have to cope with the problem of limited mobility being connected to bulky and mains-powered instruments, there is a growing demand for small-sized, high-performance and ambulatory biopotential acquisition systems in the Intensive Care Unit (ICU) and in High-dependency wards. Furthermore, electrical stimulation of specific target brain regions has been shown to alleviate symptoms of neurological disorders, such as Parkinson’s disease, essential tremor, dystonia, epilepsy etc. In recent years, the traditional practice of continuously stimulating the brain using static stimulation parameters has shifted to the use of disease biomarkers to determine the intensity and timing of stimulation. The main motivation behind closed-loop stimulation is minimization of treatment side effects by providing only the necessary stimulation required within a certain period of time, as determined from a guiding biomarker. Hence, it is clear that high-quality recording of local field potentials (LFPs) or electrocorticographic (ECoG) signals during deep brain stimulation (DBS) is necessary to investigate the instantaneous brain response to stimulation, minimize time delays for closed-loop neurostimulation and maximise the available neural data. To our knowledge, there are no commercial, small, battery-powered, wearable and wireless recording-only instruments that claim the capability of recording ECoG signals, which are of particular importance in closed-loop DBS and epilepsy DBS. In addition, existing recording systems lack the ability to provide artefact-free high-frequency (> 100 Hz) LFP recordings during DBS in real time primarily because of the contamination of the neural signals of interest by the stimulation artefacts. To address the problem of limited mobility often encountered by patients in the clinic and to provide a wide variety of high-precision sensor data to a closed-loop neurostimulation platform, a low-noise (8 nV/√Hz), eight-channel, battery-powered, wearable and wireless multi-instrument (55 × 80 mm2) was designed and developed. The performance of the realised instrument was assessed by conducting both ex vivo and in vivo experiments. The combination of desirable features and capabilities of this instrument, namely its small size (~one business card), its enhanced recording capabilities, its increased processing capabilities, its manufacturability (since it was designed using discrete off-the-shelf components), the wide bandwidth it offers (0.5 – 500 Hz) and the plurality of bioelectrical signals it can precisely record, render it a versatile tool to be utilized in a wide range of applications and environments. Moreover, in order to offer the capability of sensing and stimulating via the same electrode, novel real-time artefact suppression methods that could be used in bidirectional (recording and stimulation) system architectures are proposed and validated. More specifically, a novel, low-noise and versatile analog front-end (AFE), which uses a high-order (8th) analog Chebyshev notch filter to suppress the artefacts originating from the stimulation frequency, is presented. After defining the system requirements for concurrent LFP recording and DBS artefact suppression, the performance of the realised AFE is assessed by conducting both in vitro and in vivo experiments using unipolar and bipolar DBS (monophasic pulses, amplitude ranging from 3 to 6 V peak-to-peak, frequency 140 Hz and pulse width 100 µs). Under both in vitro and in vivo experimental conditions, the proposed AFE provided real-time, low-noise and artefact-free LFP recordings (in the frequency range 0.5 – 250 Hz) during stimulation. Finally, a family of tunable hardware filter designs and a novel method for real-time artefact suppression that enables wide-bandwidth biosignal recordings during stimulation are also presented. This work paves the way for the development of miniaturized research tools for closed-loop neuromodulation that use a wide variety of bioelectrical signals as control signals.Open Acces

Electrical Properties of Carbon Fiber Support Systems

Carbon fiber support structures have become common elements of detector designs for high energy physics experiments. Carbon fiber has many mechanical advantages but it is also characterized by high conductivity, particularly at high frequency, with associated design issues. This paper discusses the elements required for sound electrical performance of silicon detectors employing carbon fiber support elements. Tests on carbon fiber structures are presented indicating that carbon fiber must be regarded as a conductor for the frequency region of 10 to 100 MHz. The general principles of grounding configurations involving carbon fiber structures will be discussed. To illustrate the design requirements, measurements performed with a silicon detector on a carbon fiber support structure at small radius are presented. A grounding scheme employing copper-kapton mesh circuits is described and shown to provide adequate and robust detector performance.Comment: 20 pages, 11 figures, submitted to NI

Problems in assessment of novel biopotential front-end with dry electrode:A brief review

Developers of novel or improved front-end circuits for biopotential recordings using dry electrodes face the challenge of validating their design. Dry electrodes allow more user-friendly and pervasive patient-monitoring, but proof is required that new devices can perform biopotential recording with a quality at least comparable to existing medical devices. Aside from electrical safety requirement recommended by standards and concise circuit requirement, there is not yet a complete validation procedure able to demonstrate improved or even equivalent performance of the new devices. This short review discusses the validation procedures presented in recent, landmark literature and offers interesting issues and hints for a more complete assessment of novel biopotential front-end

Generalized Parity-Time Symmetry Condition for Enhanced Sensor Telemetry

Wireless sensors based on micro-machined tunable resonators are important in a variety of applications, ranging from medical diagnosis to industrial and environmental monitoring.The sensitivity of these devices is, however, often limited by their low quality (Q) factor.Here, we introduce the concept of isospectral party time reciprocal scaling (PTX) symmetry and show that it can be used to build a new family of radiofrequency wireless microsensors exhibiting ultrasensitive responses and ultrahigh resolution, which are well beyond the limitations of conventional passive sensors. We show theoretically, and demonstrate experimentally using microelectromechanical based wireless pressure sensors, that PTXsymmetric electronic systems share the same eigenfrequencies as their parity time (PT)-symmetric counterparts, but crucially have different circuit profiles and eigenmodes. This simplifies the electronic circuit design and enables further enhancements to the extrinsic Q factor of the sensors