Ultra-miniature ultra-compliant neural probes with dissolvable delivery needles: design, fabrication and characterization
Ultra-miniature ultra-compliant neural probes with dissolvable delivery needles: design, fabrication and characterization
复制标题
DOI：
10.1007/s10544-016-0125-4
复制
发表时间：
2016-12-01
影响因子：
2.8
通讯作者：
Ozdoganlar, O. Burak
中科院分区：
文献类型：
--
作者：
Khilwani, Rakesh;Gilgunn, Peter J.;Ozdoganlar, O. Burak
皮质内探针的稳定慢性功能对于实现脑机接口的临床应用至关重要。脑组织对神经探针的持续免疫反应是阻碍稳定慢性功能的主要挑战之一。文献中越来越多的证据表明，具有亚细胞尺寸的高度顺应性神经探针可以显着减少异物反应，从而增强皮质内记录的长期稳定性。由于目前的商业探针比神经元大得多，刚度高，需要新的方法来开发具有高顺应性的微型探针。在本文中，我们提出了设计，制造，并在体外评价超微型（2.7 μ m x 10 μ m横截面），超兼容（轴向为1.4 × 10（-2）μ N/μ m，和2.6 × 10（-5）μ N/μ m和1.8 × 10（-6）μ N/μ m）神经探针和相关探针。封装可生物溶解的输送针以解决上述挑战。通过聚对二甲苯-C绝缘铂布线的微米级横截面和曲折形状获得探针的高顺应性。通过有限元分析比较了超柔顺弯折探针与刚性硅探针在微动过程中组织内的应变。标准的批量微制造技术用于创建探针。包裹探头的可溶解输送针有助于无故障插入和精确放置超顺应性探头。在完成植入后，针逐渐溶解，留下超顺应性神经探针。基于旋转铸造的微成型方法用于制造针。为了证明该过程的多功能性，制造了来自不同生物可溶性材料的针以及具有不同几何形状和尺寸的二维针阵列。此外，结合抗炎药物的针被创建以显示针的共同递送潜力。开发了一种自动插入装置，用于将针包裹的探针可重复且精确地植入脑组织中。证明了针的插入没有机械故障，并且其随后的溶解。它的结论是，超小型，超顺应性探针和相关的生物可溶解的输送针可以成功地制造，和使用的超顺应性曲折的探针的结果在急剧减少施加在组织中的应变相比，刚性探针，从而显示出对慢性应用的希望。
Stable chronic functionality of intracortical probes is of utmost importance toward realizing clinical application of brain-machine interfaces. Sustained immune response from the brain tissue to the neural probes is one of the major challenges that hinder stable chronic functionality. There is a growing body of evidence in the literature that highly compliant neural probes with sub-cellular dimensions may significantly reduce the foreign-body response, thereby enhancing long term stability of intracortical recordings. Since the prevailing commercial probes are considerably larger than neurons and of high stiffness, new approaches are needed for developing miniature probes with high compliance. In this paper, we present design, fabrication, and in vitro evaluation of ultra-miniature (2.7 mu m x 10 mu m cross section), ultra-compliant (1.4 x 10(-2) mu N/mu m in the axial direction, and 2.6 x 10(-5) mu N/mu m and 1.8 x 10(-6) mu N/mu m in the lateral directions) neural probes and associated probe-encasing biodissolvable delivery needles toward addressing the aforementioned challenges. The high compliance of the probes is obtained by micron-scale cross-section and meandered shape of the parylene-C insulated platinum wiring. Finite-element analysis is performed to compare the strains within the tissue during micromotion when using the ultra-compliant meandered probes with that when using stiff silicon probes. The standard batch microfabrication techniques are used for creating the probes. A dissolvable delivery needle that encases the probe facilitates failure-free insertion and precise placement of the ultra-compliant probes. Upon completion of implantation, the needle gradually dissolves, leaving behind the ultra-compliant neural probe. A spin-casting based micromolding approach is used for the fabrication of the needle. To demonstrate the versatility of the process, needles from different biodissolvable materials, as well as two-dimensional needle arrays with different geometries and dimensions, are fabricated. Further, needles incorporating anti-inflammatory drugs are created to show the co-delivery potential of the needles. An automated insertion device is developed for repeatable and precise implantation of needle-encased probes into brain tissue. Insertion of the needles without mechanical failure, and their subsequent dissolution are demonstrated. It is concluded that ultra-miniature, ultra-compliant probes and associated biodissolvable delivery needles can be successfully fabricated, and the use of the ultra-compliant meandered probes results in drastic reduction in strains imposed in the tissue as compared to stiff probes, thereby showing promise toward chronic applications.