Shih-Rung Yeh

Flexible carbon nanotubes electrode for neural recording.

This paper demonstrates a novel flexible carbon nanotubes (CNTs) electrode array for neural recording. In this device, the CNTs electrode arrays are partially embedded into the flexible Parylene-C film using a batch microfabrication process. Through this fabrication process, the CNTs can be exposed to increase the total sensing area of an electrode. Thus, the flexible CNTs electrode of low impedance is realized. In application, the flexible CNTs electrode has been employed to record the neural signal of a crayfish nerve cord for in vitro recording. The measurements demonstrate the superior performance of the presented flexible CNTs electrode with low impedance (11.07 kohms at 1 kHz) and high peak-to-peak amplitude action potential (about 410 microV). In addition, the signal-to-noise ratio (SNR) of the presented flexible CNTs electrode is about 257, whereas the SNR of the reference (a pair of Teflon-coated silver wires) is only 79. The simultaneous recording of the flexible CNTs electrode array is also demonstrated. Moreover, the flexible CNTs electrode has been employed to successfully record the spontaneous spikes from the crayfish nerve cord. The amplitude of the spontaneous peak-to-peak response is about 25 microV.

A flexible hydrophilic-modified graphene microprobe for neural and cardiac recording.

UNLABELLED A graphene-based flexible microprobe developed by microelectromechanical system technology shows high resolution for the detection of electrophysiological signals from various bio-objects. The hydrophilization post-treatment using steam plasma was performed on the graphene surface to decrease the interfacial impedance between graphene and electrolyte, and thus improve the signal-to-noise ratio during neural and cardiac recording. The signal-to-noise ratio of the action potentials from axons of a crayfish measured by hydrophilic-modified graphene microprobe (27.8±4.0dB) is higher than that of untreated device (20.3±3.3dB). Also, the form of the QRS complex and T wave in the electrocardiogram of the zebrafish heart can be clearly distinguished using the modified device. The total measured noise levels of the overall stability of the system were 4.2μVrms (hydrophilic graphene) and 7.64μVrms (hydrophobic graphene). The graphene-based implant can be further used for in vivo, long-term recording and retina prosthesis. FROM THE CLINICAL EDITOR In this study a graphene-based flexible microprobe developed using microelectromechanical system technology was demonstrated to enable high resolution detection of electrophysiological signals, including EKG in zebrafish models. Both hydrophilic and hydrophobic graphene were studied, paving the way to potential future clinical applications of this new technology.

A three-dimensional flexible microprobe array for neural recording assembled through electrostatic actuation

We designed, fabricated and tested a novel three-dimensional flexible microprobe to record neural signals of a lateral giant nerve fiber of the escape circuit of an American crayfish. An electrostatic actuation folded planar probes into three-dimensional neural probes with arbitrary orientations for neuroscientific applications. A batch assembly based on electrostatic forces simplified the fabrication and was non-toxic. A novel fabrication for these three-dimensional flexible probes used SU-8 and Parylene technology. The mechanical strength of the neural probe was great enough to penetrate into a bio-gel. A flexible probe both decreased the micromotion and alleviated tissue encapsulation of the implant caused by chronic inflammation of tissue when an animal breathes or moves. The cortex consisted of six horizontal layers, and the neurons of the cortex were arranged in vertical structures; the three-dimensional microelectrode arrays were suitable to investigate the cooperative activity for neurons in horizontal separate layers and in vertical cortical columns. With this flexible probe we recorded neural signals of a lateral giant cell from an American crayfish. The response amplitude of action potentials was about 343 µV during 1 ms period; the average recorded data had a ratio of signal to noise as great as 30.22 ± 3.58 dB. The improved performance of this electrode made feasible the separation of neural signals according to their distinct shapes. The cytotoxicity indicated a satisfactory biocompatibility and non-toxicity of the flexible device fabricated in this work.

A cone-shaped 3D carbon nanotube probe for neural recording

A novel cone-shaped 3D carbon nanotube (CNT) probe is proposed as an electrode for applications in neural recording. The electrode consists of CNTs synthesized on the cone-shaped Si (cs-Si) tip by catalytic thermal chemical vapor deposition (CVD). This probe exhibits a larger CNT surface area with the same footprint area and higher spatial resolution of neural recording compared to planar-type CNT electrodes. An approach to improve CNT characteristics by O(2) plasma treatment to modify the CNT surface will be also presented. Electrochemical characterization of O(2) plasma-treated 3D CNT (OT-CNT) probes revealed low impedance per unit area (∼64.5 Ω mm(-2)) at 1 kHz and high specific capacitance per unit area (∼2.5 mF cm(-2)). Furthermore, the OT-CNT probes were employed to record the neural signals of a crayfish nerve cord. Our findings suggest that OT-CNT probes have potential advantages as high spatial resolution and superb electrochemical properties which are suitable for neural recording applications.

An active, flexible carbon nanotube microelectrode array for recording electrocorticograms

A variety of microelectrode arrays (MEAs) has been developed for monitoring intra-cortical neural activity at a high spatio-temporal resolution, opening a promising future for brain research and neural prostheses. However, most MEAs are based on metal electrodes on rigid substrates, and the intra-cortical implantation normally causes neural damage and immune responses that impede long-term recordings. This communication presents a flexible, carbon-nanotube MEA (CMEA) with integrated circuitry. The flexibility allows the electrodes to fit on the irregular surface of the brain to record electrocorticograms in a less invasive way. Carbon nanotubes (CNTs) further improve both the electrode impedance and the charge-transfer capacity by more than six times. Moreover, the CNTs are grown on the polyimide substrate directly to improve the adhesion to the substrate. With the integrated recording circuitry, the flexible CMEA is proved capable of recording the neural activity of crayfish in vitro, as well as the electrocorticogram of a rat cortex in vivo, with an improved signal-to-noise ratio. Therefore, the proposed CMEA can be employed as a less-invasive, biocompatible and reliable neuro-electronic interface for long-term usage.

A Battery-Less, Implantable Neuro-Electronic Interface for Studying the Mechanisms of Deep Brain Stimulation in Rat Models

Although deep brain stimulation (DBS) has been a promising alternative for treating several neural disorders, the mechanisms underlying the DBS remain not fully understood. As rat models provide the advantage of recording and stimulating different disease-related regions simultaneously, this paper proposes a battery-less, implantable neuro-electronic interface suitable for studying DBS mechanisms with a freely-moving rat. The neuro-electronic interface mainly consists of a microsystem able to interact with eight different brain regions bi-directionally and simultaneously. To minimize the size of the implant, the microsystem receives power and transmits data through a single coil. In addition, particular attention is paid to the capability of recording neural activities right after each stimulation, so as to acquire information on how stimulations modulate neural activities. The microsystem has been fabricated with the standard 0.18 μm CMOS technology. The chip area is 7.74 mm 2, and the microsystem is able to operate with a single supply voltage of 1 V. The wireless interface allows a maximum power of 10 mW to be transmitted together with either uplink or downlink data at a rate of 2 Mbps or 100 kbps, respectively. The input referred noise of recording amplifiers is 1.16 μVrms, and the stimulation voltage is tunable from 1.5 V to 4.5 V with 5-bit resolution. After the electrical functionality of the microsystem is tested, the capability of the microsystem to interface with rat brain is further examined and compared with conventional instruments. All experimental results are presented and discussed in this paper.

Flexible UV-Ozone-Modified Carbon Nanotube Electrodes for Neuronal Recording

Adv. Mater. 2010, 22, 2177–2181 2010 WILEY-VCH Verlag G Neurophysiologists have used sharpened metal electrodes to electrically stimulate neuronal activities to investigate the physiological functions of the brain. Moreover, they employed this electrical stimulation to treat diseases such as Parkinson’s disease, dystonia, and chronic pain. As neurons utilize electrical potential difference between their cell membranes to transmit electrical signals, this particular way of communication enables us to record the neuronal activity extracellularly or intracellularly. For the extracellular recording approach, the electrodes are positioned intimately next to neuron cells to record and to stimulate their electrical activity by capacitive coupling. The coupling efficacy of these electrical recordings or interventions depends significantly on the selectivity, sensitivity, charge-transfer characteristics, long-term chemical stability, and interfacial impedance between electrodes and target tissue. The most common approach to further investigate the functional behavior of neurons, is using Si-based multimicroelectrode probes fabricated by the micro-electromechanical system (MEMS) method to replace the conventional electrodes (Ag/AgCl) in the aspect of device-structure improvement and scaling down device sizes. However, Si-based MEMS electrodes are extremely rigid and cannot be deformed inside the organs; therefore, the recorded positions are easily shifted and the target tissues are consequently damaged when the animals are in motion. This will become an obstacle in future long-term implantation and real-time recording applications. An alternative method is the use of flexible electrodes presented by several groups. The authors utilized soft materials, such as poly(dimethylsiloxane), SU-8 epoxy-based negative photoresist, and polyimides, to fabricate microelectrodes that can deform while being attached to the tissues and that can also be fabricated into small-scale devices using MEMS methods. Not only would rigid Si-based MEMS probes damage target tissues, the reduced electrode size also resulted in a significantly increase in impedance that may degrade recording sensitivity and limit the stimulating current deliverable through an electrode. In order to resolve above issues, the impedance of the electrodemust be as low as possible. Carbon nanotubes (CNTs) exhibit intrinsically large surface areas (700–1000m g ), high electrical conductivity, and intriguing physicochemical properties. Most importantly, CNTs are chemically inert and biocompatible. Based on the above, the promising advantages of flexible substrates and CNTs lead the attempt of fabricating CNTs directly on flexible substrates as microelectrodes for neuronal recording. In this work, the feasibilities of growing CNTs on flexible polyimide substrates at low temperatures (400 8C) by catalyst-assisted chemical vapor deposition (CVD) and utilizing the above devices (see the schematic image in Fig. 1a and the photo in Fig. 1b) as electrodes for extracellularly neuronal recording were investigated. The electrical enhancement (by UV-ozone exposure), biocompatibility (by neuron cell cultures), long-term usage and adhesion, and the detection of action-potential signals on crayfish (using flexible UV-ozone-modified CNTelectrodes) were examined. After a series of process optimizations, the 5-nm Ni-catalyst layer and C2H2 (60 sccm)/H2 (10 sccm) process gases at 5 Torr were found to be the optimum CNT growth parameters in this work. Besides, the Au layer could facilitate CNTgrowth. Figure 1c shows that CNTs have been grown on the polyimide substrate with Au layer, while not on that without Au layer (the inset). The high-resolution transmission electron microscopy (HRTEM) image (Fig. 1d) further confirms the successful syntheses of multi-walled carbon nanotubes (MWCNTs) at 400 8C or even down to 350 8C with H2 plasma pretreatment prior to the CVD processing. As shown in the Supporting Information (Fig. S1a),

THE ENHANCEMENT OF NEURAL GROWTH BY AMINO-FUNCTIONALIZATION ON CARBON NANOTUBES AS A NEURAL ELECTRODE

This paper reports the success of amino-functionalization on multi-walled carbon nanotubes (MWCNTs) to promote neuronal cells growth on MWCNT electrode for extracellular recording, attributed to the formation of positive charge of NH(2) molecules on their surfaces. Besides, the surface of MWCNT electrode becomes hydrophilic after amino-functionalization (AF-MWCNTs) which can enhance electrical conductivity because of lower MWCNT/electrolyte interfacial impedance and higher interfacial capacitance. Durability tests show that electrical characteristics of the MWCNTs treated by 2 wt% 1,4-diaminobutane solution (2 wt%-AF-MWCNTs) can last for at least six months in air ambient. The neural recording of crayfish shows that 2 wt%-AF-MWCNTs can provide better capability on detecting action potentials of caudal photoreceptor (CPR) interneuron compared to suction glass pipette from the evidence of a higher S/N ratio (126 versus 23). The amino-functionalized MWCNT electrode is feasible for long-term recording application according to the results of biocompatibility tests. As the MWCNTs were directly synthesized on Si-based substrates by catalyst-assisted thermal chemical vapor deposition (CVD) at a low temperature (400 °C), these self-aligned MWCNT electrodes could be friendly implemented in integrated circuits fabrications.

Interfacing Neurons both Extracellularly and Intracellularly Using Carbon—Nanotube Probes with Long-Term Endurance

This study demonstrates that carbon nanotubes (CNTs) can be fabricated into probes directly, with which neural activity can be monitored and elicited not only extracellularly but also intracellularly. Two types of CNT probes have been made and examined with the escape neural circuit of crayfish, Procambarus clarkia. The CNT probes are demonstrated to have comparable performance to conventional Ag/AgCl (silver/silver cloride) electrodes. Impedance measurement and cyclic voltammetry further indicate that the CNT probes transmit electrical signals through not only capacitive coupling but also resistive conduction. The resistive conduction facilitates the recording of postsynaptic potentials and equilibrium membrane potentials intracellularly as well as the delivery of direct-current stimulation. Furthermore, delivering current stimuli for a long term is found to enhance rather than to degrade the recording capability of the CNT probes. The mechanism of this fruitful result is carefully investigated and discussed. Therefore, our findings here support the suggestion that CNTs are suitable for making biocompatible, durable neural probes of various configurations for diverse applications.

A pseudo 3D glass microprobe array: glass microprobe with embedded silicon for alignment and electrical interconnection during assembly

This study presents a process for the assembling of a pseudo 3D glass microprobe array. A glass microprobe with embedded silicon (ES) is batch fabricated by a glass reflow process. The silicon fixture and carrier for the assembly are also batch fabricated by silicon micromachining processes. First, the chips with a glass microprobe array are bonded by parylene-C to form the pseudo 3D glass microprobe array. The pseudo 3D microprobe array is then mounted on the silicon carrier. ES is employed for alignment during the assembly, and also acts as the electrical routing for signal recording. In application, the impedance of this glass microprobe is measured, and at 1 kHz it is 1.1 MΩ. Action potentials from rat brain cortex are also successfully recorded.