High-Performance Bioinstrumentation for Real-Time Neuroelectrochemical Traumatic Brain Injury Monitoring

Traumatic brain injury (TBI) has been identified as an important cause of death and severe disability in all age groups and particularly in children and young adults. Central to TBIs devastation is a delayed secondary injury that occurs in 30–40% of TBI patients each year, while they are in the hospital Intensive Care Unit (ICU). Secondary injuries reduce survival rate after TBI and usually occur within 7 days post-injury. State-of-art monitoring of secondary brain injuries benefits from the acquisition of high-quality and time-aligned electrical data i.e., ElectroCorticoGraphy (ECoG) recorded by means of strip electrodes placed on the brains surface, and neurochemical data obtained via rapid sampling microdialysis and microfluidics-based biosensors measuring brain tissue levels of glucose, lactate and potassium. This article progresses the field of multi-modal monitoring of the injured human brain by presenting the design and realization of a new, compact, medical-grade amperometry, potentiometry and ECoG recording bioinstrumentation. Our combined TBI instrument enables the high-precision, real-time neuroelectrochemical monitoring of TBI patients, who have undergone craniotomy neurosurgery and are treated sedated in the ICU. Electrical and neurochemical test measurements are presented, confirming the high-performance of the reported TBI bioinstrumentation

Design and construction of a distributed sensor NET for biotelemetric monitoring of brain energetic metabolism using microsensors and biosensors

Neurochemical pathways involved in brain physiology or disease pathogenesis are mostly unknown either in physiological conditions or in neurodegenerative diseases. Nowadays the most frequent usage for biotelemetry is in medicine, in cardiac care units or step-down units in hospitals, even if virtually any physiological signal could be transmitted (FCC, 2000; Leuher, 1983; Zhou et al., 2002). In this chapter we present a wireless device connected with microsensors and biosensors capable to detect real-time variations in concentrations of important compounds present in central nervous system (CNS) and implicated in brain energetic metabolism (Bazzu et al., 2009; Calia et al., 2009)

Dopamiinin hapettumisen lukija-anturirajapinta 65 nm CMOS teknologialla

Sensing and monitoring of neural activities within the central nervous system has become a fast-growing area of research due to the need to understand more about how neurons communicate. Several neurological disorders such as Parkinson’s disease, Schizophrenia, Alzeihmers and Epilepsy have been reported to be associated with imbalance in the concentration of neurotransmitters such as glutamate and dopamine [1] - [5]. Hence, this thesis proposes a solution for the measurement of dopamine concentration in the brain during neural communication. The proposed design of the dopamine oxidation readout sensor interface is based on a mixed-signal front-end architecture for minimizing noise and high resolution of detected current signals. The analog front-end is designed for acquisition and amplification of current signals resulting from oxidation and reduction at the biosensor electrodes in the brain. The digital signal processing (DSP) block is used for discretization of detected dopamine oxidation and reduction current signals that can be further processed by an external system. The results from the simulation of the proposed design show that the readout circuit has a current resolution of 100 pA and can detect minimum dopamine concentration of 10 μMol based on measured data from novel diamond-like carbon electrodes [6]. Higher dopamine concentration can be detected from the sensor interface due to its support for a wide current range of 1.2 μA(±600 nA). The digital code representation of the detected dopamine has a resolution of 14.3-bits with RMS conversion error of 0.18 LSB which results in an SNR of 88 dB at full current range input. However, the attained ENOB is 8-bits due to the effect of nonlinearity in the oscillator based ADC. Nonetheless, the achieved resolution of the readout circuit provides good sensitivity of released dopamine in the brain which is useful for further understanding of neurotransmitters and fostering research into improved treatments of related neurodegenerative diseases.Keskushermoston aktiivisuuden havainnointi ja tarkkailu on muodostunut tärkeäksi tutkimusalaksi, sillä tarve ymmärtää neuronien viestintää on kasvanut. Monien hermostollisten sairauksien kuten Parkinsonin taudin, skitsofrenian, Alzheimerin taudin ja epilepsian on huomattu aiheuttavan muutoksia välittäjäaineiden, kuten glutamaatin ja dopamiinin, pitoisuuksissa [1] - [5]. Aiheeseen liittyen tässä työssä esitetään ratkaisu dopamiinipitoisuuden mittaamiseksi aivoista. Esitetty dopamiinipitoisuuden lukijapiiri perustuu sekamuotoiseen etupäärakenteeseen, jolla saavutetaan matala kohinataso ja hyvä tarkkuus signaalien ilmaisemisessa. Suunniteltu analoginen etupää kykenee lukemaan ja vahvistamaan dopamiinipitoisuuden muutosten aiheuttamia virran muutoksia aivoihin asennetuista elektrodeista. Digitaalisen signaalinkäsittelyn avulla voidaan havaita dopamiinin hapettumis-ja pelkistymisvirtasignaalit, ja välittää ne edelleen ulkoisen järjestelmän muokattavaksi. Simulaatiotulokset osoittavat, että suunniteltu piiri saavuttaa 100 pA virran erottelukyvyn. Simuloinnin perustuessa hiilipohjaisiin dopamiinielektrodeihin piiri voi havaita 10 μMol dopamiinipitoisuuden [6]. Myös suurempia dopamiinipitoisuuksia voidaan havaita, sillä etupäärajapinta tukee 1.2 μA(±600 nA) virta-aluetta. Digitaalinen esitysmuoto tukee 14.3 bitin esitystarkkuutta 0.18 bitin RMS virheellä saavuttaen 88 dB dynaamisen virta-alueen. Saavutettu ENOB (tehollinen bittimäärä) on kuitenkin 8 bittiä oskillaattoripohjaisen ADC:n (analogia-digitaalimuuntimen) epälineaarisuuden takia. Saavutettu tarkkuus tuottaa hyvän herkkyyden dopamiinin havaitsemiseksi ja hyödyttää siten välittäjäainetutkimusta ja uusien hoitomuotojen kehittämistä hermostollisiin sairauksiin

Multisite monitoring of choline using biosensor microprobe arrays in combination with CMOS circuitry

A miniature device enabling parallel in vivo detection of the neurotransmitter choline in multiple brain regions of freely behaving rodents is presented. This is achieved by combining a biosensor microprobe array with a custom-developed CMOS chip. Each silicon microprobe comprises multiple platinum electrodes that are coated with an enzymatic membrane and a permselective layer for selective detection of choline. The biosensors, based on the principle of amperometric detection, exhibit a sensitivity of 157±35 µA mM-1 cm-2, a limit of detection of below 1 µM, and a response time in the range of 1 s. With on-chip digitalization and multiplexing, parallel recordings can be performed at a high signal-to-noise ratio with minimal space requirements and with substantial reduction of external signal interference. The layout of the integrated circuitry allows for versatile configuration of the current range and can, therefore, also be used for functionalization of the electrodes before use. The result is a compact, highly integrated system, very convenient for on-site measurement

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

Imaging striatal dopamine release using a nongenetically encoded near infrared fluorescent catecholamine nanosensor.

Neuromodulation plays a critical role in brain function in both health and disease, and new tools that capture neuromodulation with high spatial and temporal resolution are needed. Here, we introduce a synthetic catecholamine nanosensor with fluorescent emission in the near infrared range (1000-1300 nm), near infrared catecholamine nanosensor (nIRCat). We demonstrate that nIRCats can be used to measure electrically and optogenetically evoked dopamine release in brain tissue, revealing hotspots with a median size of 2 µm. We also demonstrated that nIRCats are compatible with dopamine pharmacology and show D2 autoreceptor modulation of evoked dopamine release, which varied as a function of initial release magnitude at different hotspots. Together, our data demonstrate that nIRCats and other nanosensors of this class can serve as versatile synthetic optical tools to monitor neuromodulatory neurotransmitter release with high spatial resolution

High-Density Neurochemical Microelectrode Array to Monitor Neurotransmitter Secretion

Neuronal exocytosis facilitates the propagation of information through the nervous system pertaining to bodily function, memory, and emotions. Using amperometry, an electrochemical technique that directly detects electroactive molecules, the sub-millisecond dynamics of exocytosis are revealed and the modulation of neurotransmitter secretion due to neurodegenerative diseases or pharmacological treatments can be studied. The method of detection using amperometry is the exchange of electrons due to a redox reaction at an electrochemically sensitive electrode. As electroactive molecules, such as dopamine, undergo oxidation, electrons are released from the molecule to the electrode and an oxidation current is generated and recorded. Despite the significance of traditional single-cell amperometry, it is a costly, labor-intensive, and low-throughput, procedure. The focus of this dissertation is the development of a monolithic CMOS-based neurochemical sensing system that can provide a high-throughput of up to 1024 single-cell recordings in a single experiment, significantly reducing the number of experiments required for studying the effects of neurodegenerative diseases or new pharmacological treatments on the exocytosis process. The neurochemical detection system detailed in this dissertation is based on a CMOS amplifier array that contains 1024 independent electrode-amplifier units, each of which contains a transimpedance amplifier with comparable noise performance to a high-quality electrophysiology amplifier that is used for traditional single-cell amperometry. Using this novel technology, single exocytosis events are monitored simultaneously from numerous single-cells in experiments to reveal the secretion characteristics from groups of cells before and after pharmacological treatments which target the modulation of neurotransmitters in the brain, such as drugs for depression or Parkinson\u27s disease

A 16 x 16 CMOS amperometric microelectrode array for simultaneous electrochemical measurements

There is a requirement for an electrochemical sensor technology capable of making multivariate measurements in environmental, healthcare, and manufacturing applications. Here, we present a new device that is highly parallelized with an excellent bandwidth. For the first time, electrochemical cross-talk for a chip-based sensor is defined and characterized. The new CMOS electrochemical sensor chip is capable of simultaneously taking multiple, independent electroanalytical measurements. The chip is structured as an electrochemical cell microarray, comprised of a microelectrode array connected to embedded self-contained potentiostats. Speed and sensitivity are essential in dynamic variable electrochemical systems. Owing to the parallel function of the system, rapid data collection is possible while maintaining an appropriately low-scan rate. By performing multiple, simultaneous cyclic voltammetry scans in each of the electrochemical cells on the chip surface, we are able to show (with a cell-to-cell pitch of 456 μm) that the signal cross-talk is only 12% between nearest neighbors in a ferrocene rich solution. The system opens up the possibility to use multiple independently controlled electrochemical sensors on a single chip for applications in DNA sensing, medical diagnostics, environmental sensing, the food industry, neuronal sensing, and drug discovery