A multichannel neural probe with embedded microfluidic channels for simultaneous in vivo neural recording and drug delivery

Abstract

Multi-functional neural probes integrated with various stimulation modalities are becoming essential tools in neuroscience to study the brain more effectively. In this paper, we present a new multi-functional neural probe that allows chemical stimulation through drug delivery and simultaneous recording of individual neuron signals through a microelectrode array. By embedding microchannels in silicon using a proposed glass reflow process, we successfully fabricated 40 μm thick silicon neural probes suitable for small animal experiments. The electrochemical impedance spectroscopy confirms that impedance of iridium microelectrodes is low enough (<1 MΩ at 1 kHz) to measure neural signals. Flow rate characterization in a 0.9% w/v agarose gel shows the capability to deliver a small volume of drugs (<1 μl) at a controlled flow rate. We demonstrate the viability and potential of this new probe by conducting in vivo experiments on mice. Because of the proposed compact structure, both action potentials of individual neurons and local field potentials (LFP) at the thalamus region of a mouse brain were successfully detected with a noise level of ~30 μVpp. Furthermore, we successfully induced absence seizure by injecting seizure-inducing drugs (baclofen) at a local target region and observed distinctive changes in neural signal patterns. Specifically, spike-wave discharge (SWD), which is an indicative signal pattern of absence seizure, was successfully recorded. These signals were also directly compared to SWD detected after inducing absence seizure through direct injection of baclofen through the abdomen. This work demonstrates the potential of our multi-functional neural probes for use in effective investigation of brain functions and disorders by using widely available mouse models.

Next-generation probes, particles, and proteins for neural interfacing

“…Early advances in this sense relied on fabrication schemes known from MEMS technology and wafer bonding to develop silicon probes with microfluidic channels ( 230 ). These approaches have been translated to, for example, SU-8, parylene, and elastomeric probes ( 58 , 231 , 232 ).…”

Neural probes with multi-drug delivery capability

“…1) was fabricated based on four major steps: 1) etching the cavities and creating a glass cover to form the embedded microfluidic channels in the silicon substrate, 2) patterning of a microelectrode array on top, 3) patterning an inlet and an outlet to provide an interface to the microfluidic channels, and 4) releasing the structure from the backside to create the final shape. 11 Design, fabrication, and packaging of 3-inlet SHM To achieve multi-drug delivery with our chemtrode, we designed and fabricated a SHM in a 3-inlet polydimethylsiloxane (PDMS) microfluidic chip (Fig. To improve the process yield during this step, multiple narrow cavities are first created to prevent the glass from completely filling the cavities (see the cross-section of the chemtrode shank in Fig.…”

“…When infusing various concentrations of TTX, we observed a decrease in the firing rates of the four sorted neural spike signals. 11 In addition, since neural probe systems are implanted directly above mouse heads, the size of the total system is critical for long- term chronic in vivo experiments. S5).…”

“…[9][10][11][12][13][14][15][16] More specifically, once implanted, neither concentrations nor types of drugs can be altered. [9][10][11][12][13][14][15][16] More specifically, once implanted, neither concentrations nor types of drugs can be altered.…”

Polymer SU-8-Based Microprobes for Neural Recording and Drug Delivery

“…Changes in the response properties of isolated neurons during drug delivery confirmed the validity of this approach. Since then, efforts have been devised toward precisely control and monitor fluid movements (Lin and Pisano, 1999;McAllister et al, 2000;Rathnasingham et al, 2004;Neeves et al, 2006;Papageorgiou et al, 2006;Foley et al, 2009;Rohatgi et al, 2009;Pongrácz et al, 2013;Lee et al, 2015). Recently, multi-shank fluidic silicon probes have been developed for neuroscientific applications (Seidl et al, 2010;Frey et al, 2011;John et al, 2011;Spieth et al, 2011).…”