This work presents a new fabrication technology for silicon-based neural probe devices and their assembly into two-dimensional (2D) as well as three-dimensional (3D) microprobe arrays for neural recording. The fabrication is based on robust double-sided deep reactive ion etching of standard silicon wafers and allows full 3D control of the probe geometry. Wafer level electroplating of gold pads was performed to improve the 3D assembly into a platform. Lithography-based probe-tracking features for quality management were introduced. Probes for two different assembly methods, namely direct bonding to a flexible micro-cable and platform-based out-of-plane interconnection, were produced. Systems for acute and sub-chronic recordings were assembled and characterized. Recordings from rats demonstrated the recording capability of these devices.
This paper reports on the design, fabrication and characterization of silicon-based microprobes for simultaneous neural recording and drug delivery. The fabrication technology is based on two-stage deep reactive ion etching combined with silicon wafer bonding and grinding to realize channel structures integrated in needle-like probe shafts. Liquids can be supplied to microfluidic devices via in-plane and out-of-plane ports. The liquid is dispensed at circular out-of-plane ports with a diameter of 25 μm and rectangular in-plane ports with dimensions of 50 × 50 μm 2. Two-shaft probes with a pitch between shafts of 1.0 and 1.5 mm were realized. The probe shafts have a length of 8 mm and rectangular cross-sections of w × h (w = 250 μm and h = 200 or 250 μm). Each shaft contains one or two fluidic channels with a cross-section of 50 × 50 μm 2. In addition, each probe shaft comprises four recording sites with diameters of 20 μm close to the outlet ports. Mechanical and fluidic characterization demonstrated the functionality of the probes. Typical infusion rates of 1.5 μL min −1 are achieved at a differential pressure of 1 kPa. The Pt-gray electrodes have an average electrode impedance of 260 ± 59 k at 1 kHz.
Extracellular recordings from the brain are the basis for the fundamental understanding of the complex interaction of electrical signals in neural information transfer. Going beyond wire electrodes and bundles of electrode wires such as tetrodes, multielectrode arrays based on silicon technologies are receiving growing attention, since they enable a pronounced increase in the number of recording sites per probe shaft. In this paper, recent innovations contributed by the authors to the development of probe arrays based on microelectromechanical system (MEMS) technologies within the EU-funded research project NeuroProbes are described. The resulting structures include passive electrode arrays based on single-shaft and four-shaft probes comprising nine planar electrodes per shaft with lengths of up to 8 mm. Further, active probe arrays with complementary metal-oxide-semiconductor (CMOS) circuitry integrated on the probe shaft, enabling the arrangement of 188 electrodes in two columns along a 4-mm-long probe shaft with an electrode pitch of only 40 µm, are described. These active probes were developed for an electronic depth control. Further, the paper reports assembly technologies for combining the probe arrays with highly flexible ribbon cables. Applications of the probes in in vivo experiments are summarized.
processes to destroy microorganisms. The concentration of the released substances changes spatially and temporally and is a biochemical fingerprint of the biological state. However, such biologically relevant processes occur on temporal (ms) and spatial (nm) scales that are difficult to access using established methods. [3] For example, electrochemical methods, such as amperometry or voltammetry, lack the required spatial resolution determined by the number of electrodes and are invasive as the microelectrodes penetrate the tissue. [4] On the other hand, optical methods provide often only indirect information, for example, by labeling cellular components [5,6] or suffering from photobleaching. [7] In this context, nanomaterials, such as single-wall carbon nanotubes (SWCNTs), have emerged as promising building blocks to capture these dynamics. [3,8] In addition to a high surface-to-volume ratio that makes them sensitive to single-molecule detection, [9][10][11][12] their surface can be chemically tailored. [13][14][15][16][17] Thus, SWCNTs have already been used for several bioimaging studies [18,19] and the detection of numerous analytes such as reactive oxygen species, [20][21][22][23] small molecules like nitroaromatics [24,25] or neurotransmitters, [26,27] proteins, [28][29][30] sugars, [31] enzymes, [32] or bacteria. [33] Due to their fluorescence in the near-infrared (NIR, 850-1700 nm), which shows no bleaching or blinking, they represent stable fluorophores, whose emission falls within the biological transparency window. [34] Here, Biochemical processes are fast and occur on small-length scales, which makes them difficult to measure. Optical nanosensors based on singlewall carbon nanotubes (SWCNTs) are able to capture such dynamics. They fluoresce in the near-infrared (NIR, 850-1700 nm) tissue transparency window and the emission wavelength depends on their chirality. However, NIR imaging requires specialized indium gallium arsenide (InGaAs) cameras with a typically low resolution because the quantum yield of normal Si-based cameras rapidly decreases in the NIR. Here, an efficient one-step phase separation approach to isolate monochiral (6,4)-SWCNTs (880 nm emission) from mixed SWCNT samples is developed. It enables imaging them in the NIR with high-resolution standard Si-based cameras (>50× more pixels). (6,4)-SWCNTs modified with (GT) 10 -ssDNA become highly sensitive to the important neurotransmitter dopamine. These sensors are 1.7× brighter and 7.5× more sensitive and allow fast imaging (<50 ms). They enable high-resolution imaging of dopamine release from cells. Thus, the assembly of biosensors from (6,4)-SWCNTs combines the advantages of nanosensors working in the NIR with the sensitivity of (Si-based) cameras and enables broad usage of these nanomaterials.
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