DEEP BRAIN TARGETING STRATEGY FOR BARE PARYLENE NEURAL PROBE ARRAYS

We present a Parylene neural microprobe array and the first demonstration of deep brain (> 5 mm) implantation of bare polymer probes, enabled by a novel micropackaging technique. Targeting brain sites below the surface of the cortex with soft polymer probes typically requires bulky overcoats or insertion shuttles, which greatly increase probe dimensions and tissue damage, negating advantages of the flexible polymers. We achieved deep brain implantation of bare polymer probes by temporarily shortening their effective length using a biodegradable brace, thereby achieving the required transient increase in stiffness (Figure 1). This surgical approach solves a key technical obstacle preventing the widespread adoption of polymer microprobes. Here, we present mechanical, histological, and electrochemical evidence to support this approach. Figure 1: (a) Buckling force threshold of bare probes is lower than that required for insertion, resulting in deformation. (b) PEG brace reduces the effective length of probes, increasing the buckling force threshold and enabling successful implantation. Buckling force F is modeled by the equation above in which k is the column effective length factor, E is the Young’s modulus, I is the moment of inertia, and L is the probe’s length. (c) Exposed probes are inserted to brain, PEG brace is dissolved in saline, and probes inserted to desired depth (5.5 mm). INTRODUCTION Soft polymers offer an appealing alternative to silicon, glass, or metal materials for the creation of neural probes. Rigid probes suffer inevitable signal degradation over time as chronic tissue irritation leads to an immune cascade that eventually may wall off of the implant [1, 2]. Rigid probes have successfully achieved high-quality recordings on the scale of a few months, but this falls short of long-term goals desired to produce effective, life-long brain machine interfaces [3, 4]. Whereas metals and silicon have Young’s moduli on the order of hundreds of GPa, the stiffness of brain tissue is orders of magnitudes softer, at around 10 GPa. This disparity between the stiffness of brain tissue and implantable neural probes can lead to tissue damage as micro-motion of the brain causes chronic tissue irritation. It is speculated that the use of soft probes might mitigate this damage and attenuate the immune response and the glial cell sheath that impact achievable signal-to-noise ratios over time [5]. In one study, soft Parylene probes were shown to induce only a 12-17% neuronal loss around the implantation site compared to rigid silicon probes which incurred 40% neuronal loss at 4 weeks post-implantation [6]. The reduced stiffness of polymers, however, presents a technical challenge for surgical insertion into brain tissue. Polymer probes must be temporarily stiffened in order to penetrate brain tissue and for accurate surgical placement, typically via bulky biodegradable overcoats or insertion shuttles [1, 7, 8] which can increase probe cross-section by 1.2-3,900x’s thereby significantly adding to acute tissue injury [1, 9]. The use of coatings or stiffeners can lead to other difficulties as well. Coatings may dull probe tips [9], cover electrode recording sites during surgery [7], or cause the probes to curl as the coating dries [10]. Retraction of a stiffener post-insertion may lead to the movement of a probe away from its target site, interfering with proper probe placement [8]. The need for temporary stiffening of probes during implantation has limited development of polymer probes to designs with short shanks (typically 1-2 mm), as shorter probes have larger buckling force thresholds, and has constrained recording sites to superficial cortical structures [1, 11, 12]. Our strategy overcomes these issues, and opens the door for the large scale acquisition of neural recordings from deep brain structures such as the cornu ammonis (CA1, CA3) and dentate gyrus (DG) in the hippocampus.