Karsten Seidl

Fabrication technology for silicon-based microprobe arrays used in acute and sub-chronic neural recording

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.

ENHANCING THE YIELD OF HIGH-DENSITY ELECTRODE ARRAYS THROUGH AUTOMATED ELECTRODE SELECTION

Recently developed CMOS-based microprobes contain hundreds of electrodes on a single shaft with inter-electrode distances as small as 30 μm. So far, neuroscientists needed to select electrodes manually from hundreds of electrodes. Here we present an electronic depth control algorithm that allows to select electrodes automatically, hereby allowing to reduce the amount of data and locating those electrodes that are close to neurons. The electrodes are selected according to a new penalized signal-to-noise ratio (PSNR) criterion that demotes electrodes from becoming selected if their signals are redundant with previously selected electrodes. It is shown that, using the PSNR, interneurons generating smaller spikes are also selected. We developed a model that aims to evaluate algorithms for electronic depth control, but also generates benchmark data for testing spike sorting and spike detection algorithms. The model comprises a realistic tufted pyramidal cell, non-tufted pyramidal cells and inhibitory interneurons. All neurons are synaptically activated by hundreds of fibers. This arrangement allows the algorithms to be tested in more realistic conditions, including backgrounds of synaptic potentials, varying spike rates with bursting and spike amplitude attenuation.

CMOS-Based High-Density Silicon Microprobe Arrays for Electronic Depth Control in Intracortical Neural Recording

This paper reports on a novel high-density CMOS-based silicon microprobe array for intracortical recording applications. In contrast to existing systems, CMOS multiplexing units are integrated directly on the slender, needle-like probe shafts. Single-shaft probes and four-shaft combs have been realized with 188 and 752 electrodes, respectively, with a pitch of 40 μm arranged in two columns along 4-mm-long probe shafts. Rather than performing a mechanical translation of the probe shaft relative to the brain tissue to optimize the distance between electrodes and neurons, the electrode position is adjusted by electronically switching between the different electrodes along the shaft. The paper presents the probe concept, the CMOS circuitry design, the applied post-CMOS fabrication process, and the assembled probe systems.

Microprobe Array with Low Impedance Electrodes and Highly Flexible Polyimide Cables for Acute Neural Recording

This paper reports on a novel type of silicon- based microprobes with linear, two and three dimensional (3D) distribution of their recording sites. The microprobes comprise either single shafts, combs with multiple shafts or 3D arrays combining two combs with 9, 36 or 72 recording sites, respectively. The electrical interconnection of the probes is achieved through highly flexible polyimide ribbon cables attached using the MicroFlex Technology which allows a connection part of small lateral dimensions. For an improved handling, probes can be secured by a protecting canula. Low-impedance electrodes are achieved by the deposition of platinum black. First in vivo experiments proved the capability to record single action potentials in the motor cortex from electrodes close to the tip as well as body electrodes along the shaft.

In-plane silicon probes for simultaneous neural recording and drug delivery

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 µm2. 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 µm2. 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 kΩ at 1 kHz.

Two-Dimensional Multi-Channel Neural Probes With Electronic Depth Control

This paper presents multi-electrode arrays for in vivo neural recording applications incorporating the principle of electronic depth control (EDC), i.e., the electronic selection of recording sites along slender probe shafts independently for multiple channels. Two-dimensional (2D) arrays were realized using a commercial 0.5- μm complementary-metal-oxide-semiconductor (CMOS) process for the EDC circuits combined with post-CMOS micromachining to pattern the comb-like probes and the corresponding electrode metallization. A dedicated CMOS integrated front-end circuit was developed for pre-amplification and multiplexing of the neural signals recorded using these probes.

A floating 3D silicon microprobe array for neural drug delivery compatible with electrical recording

This paper reports on the design, fabrication, assembly and characterization of a three-dimensional silicon-based floating microprobe array for localized drug delivery to be applied in neuroscience research. The microprobe array is composed of a silicon platform into which up to four silicon probe combs with needle-like probe shafts can be inserted. Two dedicated positions in the array allow the integration of combs for drug delivery. The implemented comb variants feature 8 mm long probe shafts with two individually addressable microchannels incorporated in a single shaft or distributed to two shafts. Liquid supply to the array is realized by a highly flexible 250 µm thick multi-lumen microfluidic cable made from polydimethylsiloxane (PDMS). The specific design concept of the slim-base platform enables floating implantation of the array in the small space between brain and skull. In turn, the flexible cable mechanically decouples the array from any microfluidic interface rigidly fixed to the skull. After assembly of the array, full functionality is demonstrated and characterized at infusion rates from 1 to 5 µL min−1. Further, the effect of a parylene-C coating on the water vapour and osmotic liquid water transport through the PDMS cable walls is experimentally evaluated by determining the respective transmission rates including the water vapour permeability of the used PDMS type.

Ultracompact optrode with integrated laser diode chips and SU-8 waveguides for optogenetic applications

This paper reports on the design, fabrication and characterization of an innovative silicon-based neural probe with optical functionality. This so-called optrode is intended as an ultracompact tool for optogenetic applications in neuroscientific research. Beside platinum microe-lectrodes for electrical recording applications, bare laser diode (LD) chips combined with waveguides (WGs) implemented in the negative photoresist SU-8 are integrated on the probe. The assembly of the bare LD chips applies flip-chip and wire bonding and benefits of a lateral alignment accuracy better ±5 μm required for the efficient coupling of light into the 15-μm-wide and 13-μm-high WGs. Undesired tissue illumination due to stray light is effectively blocked using a micromachined cover chip adhesively bonded to the probe base. Probe shafts with a length of up to 8 mm and a thickness of 50 μm carrying four electrodes and two WGs each have been realized. The maximum optical output power per WG was measured to be 29.7 mW/mm2 for LDs with a center wavelength of 650 nm.

CMOS-Based High-Density Silicon Microprobe Arrays for Electronic Depth Control in Intracortical Neural Recording–Characterization and Application

This paper reports on the characterization and intracortical recording performance of high-density complementary-metal-oxide-semiconductor (CMOS)-based silicon microprobe arrays. They comprise multiplexing units integrated on the probe shafts being part of the signal transmission path. Their electrical characterization reveals a negligible contribution on the electrode impedances of 139 ±11 kΩ and 1.2 ±0.1 MΩ and on the crosstalks of 0.12% and 0.98% for iridium oxide ( IrOx) and platinum (Pt) electrodes, respectively. The power consumption of the single-shaft probe was found to be 57.5 μW during electrode selection. The noise voltage of the switches was determined to be 5.6 nV/√Hz; it does not measurably affect the probe performance. The recording selectivity of the electrode array is demonstrated by electrical potential measurements in saline solution while injecting a stimulating current using an external probe. In-vivo recordings in anesthetized rats using all 188 electrodes with a pitch of 40.7 μm are presented and analyzed in terms of single neural activity and signal-to-noise ratio. The concept of electronic depth control is proven by performing mechanical translation of the probe shaft while electronically switching to adjacent electrodes to compensate the mechanical shift.

CMOS-Based High-Density Silicon Microprobe Array for Electronic Depth Control in Neural Recording

This paper reports on a novel CMOS-based high-density silicon microprobe array for intracortical recording applications. In contrast to existing systems, CMOS multiplexing units are integrated on the slender, needle-like probe shaft 160 ¿m in width. In the present implementation an unequaled number of 188 electrodes (diameter 20 ¿m, pitch 40 ¿m) are arranged in two columns along the 4-mm-long probe shaft. The on-shaft integration of electronics is motivated by the requirement to discriminate single action potentials in extracellular recordings necessitating a close proximity between the neuron of interest and the recording electrode. Instead of a mechanical movement of the probe shaft carrying the electrode, the position adjustment during long-term recordings is performed by switching between different electrodes arranged in a dense array. The paper presents the probe concept, the post-CMOS fabrication process and initial measurements evaluating electrode impedance and probe performance during measurements in saline solution.