Free-standing nanowire transistor bio-probes for intracellular and implanted recording

 描述(申请人提供)：生物电子接口是生物研究和生物医学应用中的关键部件。由于记录电极和活细胞之间的尺寸和机械失配，现有技术面临着许多内在的挑战，这导致其性能、生物兼容性和寿命受到限制，特别是在植入应用方面。根本的问题是：我们能否重新审视这种接口的基本单元，自下而上地开发生物探针，使人工电子和生物网络能够以更自然的方式连接起来？纳米线基场效应晶体管(FET)传感器由于其纳米尺度的尺寸和结构，在检测生物信号以及与活细胞的丰富相互作用方面表现出高灵敏度。这使得它们非常有希望成为构建高性能、微创生物探针的基础，用于体外和体内应用。这一R21项目的总体目标是开发超小型独立纳米线晶体管生物探针，用于细胞内多路研究和植入型生物医学应用。在我们正在进行的实验中，我们发现可以将纳米场效应晶体管(NanFET)人工集成到扭结的硅纳米线(SiNW)中，构建一个三维(3D)纳米传感器，它可以无创地进入活的心肌细胞，获得完整的细胞内动作电位。我们假设这种方法可以发展成一个通用的平台，用于与不同类型的细胞接口，更重要的是，通过结合可生物降解的牺牲层来构建与活细胞具有独特相互作用的可植入生物探针，该牺牲层允许植入后原位形成灵活的3D结构，以促进与更坚硬的支撑体以外的活性细胞的更紧密的相互作用。这一总体假设将在以下具体目标的实验中得到解决：(1)开发促进纳米FET与细胞之间强烈相互作用的通用协议，以及(2)开发针对细胞内记录和植入应用而优化的超小独立纳米FET探针。这一系统的研究将对纳米线-细胞相互作用有深刻的理解和控制，并为将基于纳米线的探针用于生理研究和生物医学应用提供可靠的协议。此外，植入后原位形成的具有三维(3D)柔性结构的独立探头的独特设计，使纳米FET在3D自由空间中呈现，而没有笨重的支撑衬底，由于探头尺寸显著减小，与组织的机械匹配更好，导致组织反应更少，与细胞更自然地耦合，因此可以极大地提高信号质量和重复性，并扩展纳米电子传感器的功能。我们的研究将发现辅助设备、假肢和脑机接口在生物医学上的广泛应用。

 DESCRIPTION (provided by applicant): The bio-electronic interface is a key component in biological research and biomedical applications. Existing techniques face many intrinsic challenges due to the size and mechanical mismatch between recording electrodes and live cells, which leads to limitations in their performance, biocompatibility and lifetime, especially fr implanted applications. The fundamental question is: can we re-examine the basic unit of such interface to develop bio-probes from bottom-up, so that the artificial electronics and the biological network can be bridged in a more natural way? Nanowire-based field-effect transistor (FET) sensors have shown high sensitivity in detecting biological signals as well as rich interactions with live cells, owing to their nanoscale size and structure. This makes them very promising building blocks for constructing high-performance, minimally-invasive bio-probes for in vitro and in vivo applications. The overall goal of this proposed R21 project is to develop ultra-small free-standing nanowire transistor bio-probes for multiplexed intracellular study and implanted biomedical applications. In our on-going experiments, we discovered that a nanoscale field-effect transistor (nanoFET) can be synthetically integrated in a kinked Si nanowire (SiNW) to build a three-dimensional (3D) nano-sensor, which can non-invasively enter live cardiomyocytes to obtain full intracellular action potentials. We hypothesize that this method can be developed into a general platform for interfacing with different types of cells, and more importantly, for building implantable bio-probes with unique interplay with live cells, by incorporating biodegradable sacrificial layers that allow post-implantation in situ formation of flexible 3D structures to promote tighter interactions with active cells away from the more rigid supportive body. This overall hypothesis will be addressed in the experiments of the following Specific Aims: (1) to develop general protocols for promoting strong nanoFET-cell interaction and (2) to develop ultra-small free- standing nanoFET probes optimized for intracellular recording and implanted applications. The systematic study here would bring insightful understanding and control of the nanowire-cell interaction, and provide robust protocols for using nanowire-based probes for physiological study and biomedical applications. In addition, the unique design of free-standing probe with three-dimensional (3D) flexible structure formed in situ after implantation, which presents the nanoFET in 3D free space without bulky supporting substrates, could greatly enhance signal quality and reproducibility, and expand the functionality of the nanoelectronic sensors, due to the significantly reduced probe size and better mechanical matching with the tissue, leading to less tissue reaction, and more natural coupling with cells. Our study would find broad biomedical applications for assistive devices, prosthesis and brain-machine interface.