Optrode array for optical neural stimulation and recording

光学方法正在神经科学、医学成像和诊断学等领域得到确立。例如，光遗传学尽管是一个新兴的研究领域，但已被自然方法评为2010年年度方法。我们建议开发和测试一种新的器件结构，以促进三维深层组织光的穿透和收集，具有同时对不同波长进行时空调制的能力，以促进在光学神经刺激和记录方面的广泛应用。由光学透明针组成的3D光学电极阵列可以直接穿透组织1毫米，从而创建多个独立的光传播路径，从而避免由于组织吸收和散射而导致的衰减。我们将开发适用于可见光甚至近红外应用的二氧化硅阵列。这项研究的学术价值在于解决了几乎所有光激发模式的障碍，在这些模式中，穿透深度是由光电极长度而不是波长决定的。我们建议利用为穿透电极而开发的大量微制造方法，以实现与外部方法相比在光学传输和接收方面的相同优势。更广泛的影响：这项工作可能会产生多重、广泛的和潜在的变革性影响。虽然我们的重点是光遗传神经刺激和记录，但光电极阵列设备在基础神经科学研究、高选择性光动力疗法以及用于诊断和治疗的深层组织成像中都有应用。从应用神经科学和神经工程学的角度来看，光电极阵列设备将有助于更深入地进入神经组织，例如中枢或外周神经束中的轴突束。更深入地进入多个刺激/记录部位可能使神经系统紊乱或疾病后失去的运动或感觉功能得以恢复。潜在的代表性应用包括瘫痪后恢复手握力或站立，以及失去肢体后皮肤和本体感觉反馈的恢复。从教育角度来看，拟议研究的内在跨学科和互动性将为生物光子学、微制造、神经工程和基础神经科学方面的培训提供独特的机会，并将与犹他大学正在进行的主要研究和教育举措产生协同作用。从多样性和外展的角度来看，生物工程系在吸引和指导女性工程师方面取得的成功(PI是该系的兼职教员，而联席PI是终身教职跟踪成员)，加上最近加强的全学院和全大学的外联和招聘努力，将有助于将代表不足的人群带入新兴的神经工程增长领域。

Optical methods are becoming established in the fields of neuroscience, medical imaging and diagnostics, etc. Optogenetics, for example, despite being a nascent field of study, has been named the Method of the Year 2010 by Nature Methods. We propose to develop and test a novel device structure to facilitate three-dimensional deep-tissue light penetration and collection with capabilities for simultaneous spatiotemporal modulation of different wavelenghts to advance a broad range of applications in optical neural stimulation and recording. A 3D optrode array consisting of optically transparent needles can penetrate 1 mm directly into tissue, thereby creating multiple independent paths for light propagation that avoid attenuation due to tissue absorption and scattering. We will develop SiO2 arrays suitable for visible and even NIR applications. The intellectual merits of this research lie in the addressing the barrier for nearly all modes of optical excitation where penetration depth is determined by optrode length, not by wavelength. We propose to leverage off of the extensive body of microfabrication methods developed for penetrating electrodes to achieve the same advantages for optical delivery and reception as compared to external approaches. Broader Impact: Multiple, broadly enabling, and potentially transformative, impacts may emerge from this work. Although our focus is on optogenetic neural stimulation and recording, optrode array devices have application in basic neuroscience research, highly selective photodynamic therapy, and deep tissue imaging for diagnostics and therapy. From an applied neuroscience and neuroengineering perspective, the optrode array device will facilitate deeper access into neural tissue, such as axon bundles within the fasicles of central or peripheral nerves. Deeper access across multiple stimulation/recording sites may enable restoration of lost motor or sensory function after nervous system disorders or disease. Potential representative applications, among many, include restoration of hand grasp or stance after paralysis, and restoration of cutaneous and proprioceptive sensory feedback after limb loss. From an educational perspective, the inherently interdisciplinary and interactive nature of the proposed research will provide unique opportunities for training in biophotonics, microfabrication, neuroengineering, and basic neuroscience, and will interact synergistically with ongoing major research and educational initiatives at the University of Utah. From diversity and outreach perspectives, the established success of the Bioengineering Department (of which the PI is an adjunct-faculty member, and the co-PI a tenure-track member) in attracting and mentoring female engineers, along with recently enhanced College- and University-wide outreach and recruitment efforts, will help bring underrepresented populations into the emerging neuro-engineering growth area.