Insertion of Flexible Neural Probes Using Rigid Stiffeners Attached with Biodissolvable Adhesive

Summary

Insertion of flexible neural microelectrode probes is enabled by attaching probes to rigid stiffeners with polyethylene glycol (PEG). A unique assembly process ensures uniform and repeatable attachment. After insertion into tissue, the PEG dissolves and the stiffener is extracted. An in vitro test method evaluates the technique in agarose gel.

Abstract

Microelectrode arrays for neural interface devices that are made of biocompatible thin-film polymer are expected to have extended functional lifetime because the flexible material may minimize adverse tissue response caused by micromotion. However, their flexibility prevents them from being accurately inserted into neural tissue. This article demonstrates a method to temporarily attach a flexible microelectrode probe to a rigid stiffener using biodissolvable polyethylene glycol (PEG) to facilitate precise, surgical insertion of the probe. A unique stiffener design allows for uniform distribution of the PEG adhesive along the length of the probe. Flip-chip bonding, a common tool used in microelectronics packaging, enables accurate and repeatable alignment and attachment of the probe to the stiffener. The probe and stiffener are surgically implanted together, then the PEG is allowed to dissolve so that the stiffener can be extracted leaving the probe in place. Finally, an in vitro test method is used to evaluate stiffener extraction in an agarose gel model of brain tissue. This approach to implantation has proven particularly advantageous for longer flexible probes (>3 mm). It also provides a feasible method to implant dual-sided flexible probes. To date, the technique has been used to obtain various in vivo recording data from the rat cortex.

Introduction

Microelectrode arrays are an essential tool in neuroscience as well as emerging clinical applications such as prosthetics. In particular, penetrating micro-electrode probes enable stimulation and recording of neuronal activity through close contact with cells in the brain, spinal cord, and peripheral nerves. A major challenge for implanted neural probes is stability and longevity of the stimulation and recording functions. Modeling and experimental studies of the interaction between microelectrode probes and neural tissue have suggested that one mechanism for degradation is micro-tearing of neural tissue due to slight relative motion between the probe and tissue

Protocol

1. Assembly of Probe to Stiffener

This section of the protocol describes fabrication of a silicon stiffener, and the assembly of a thin-film polymer probe to the stiffener. Figure 1 illustrates a typical polymer neural probe along with the proposed stiffener. The details of the stiffener design are shown in Figure 2. The novel feature of this design is the shallow "wicking" channel running along its length which is used to distribute liquid adhesive during assembly. The wider portion of the stiffener is a tab for handling during assembly and surgical insertion. A reservoir on the tab connects to the chann....

Results

This insertion technique was used in conjunction with LLNL thin-film polyimide probes, which have passed ISO 10993 biocompatibility standards and are intended for chronic implantation. A typical thin-film polyimide probe is illustrated in Figure 1 along with a silicon stiffener that is approximately 10 mm long in the narrow region. This stiffener has one wicking channel running along its length, as shown in Figure 2. Figure 3 illustrates the mimcrofabrication process u.......

Discussion

The method described here provides a well-controlled process to attach thin-film polymer probes to separate stiffeners with a biodissolvable adhesive. Also presented is the recommended surgical procedure to implement these removable stiffeners and a technique to validate the procedure in vitro for a given probe-stiffener configuration. Since the stiffener can be made arbitrarily rigid, the method can facilitate insertion of relatively long probes (>3 mm). As such, the insertion method is expected to be an e.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Polyethylene glycol, 10,000 g/mol	Sigma Aldrich	309028
Agarose	Sigma Aldrich	A9539
Flexible Sub-micron Die Bonder	Finetech	Fineplacer lambda
Micromanipulator	KOPF	1760-61
Digital Microscope	Hirox	KH-7700
Dual Illumination Revolver Zoom Lens	Hirox	MXG-2500REZ
Precision Motorized Actuator	Newport	LTA-HS	w/ CONEX-CC controller