Department of Chemistry and Chemical Biology and ‡John A. Paulson School of Engineering and Applied Science, Harvard University , Cambridge, Massachusetts 02138, United States.
Nano Lett. 2015 Oct 14;15(10):6979-84. doi: 10.1021/acs.nanolett.5b02987. Epub 2015 Sep 2.
Syringe-injectable mesh electronics with tissue-like mechanical properties and open macroporous structures is an emerging powerful paradigm for mapping and modulating brain activity. Indeed, the ultraflexible macroporous structure has exhibited unprecedented minimal/noninvasiveness and the promotion of attractive interactions with neurons in chronic studies. These same structural features also pose new challenges and opportunities for precise targeted delivery in specific brain regions and quantitative input/output (I/O) connectivity needed for reliable electrical measurements. Here, we describe new results that address in a flexible manner both of these points. First, we have developed a controlled injection approach that maintains the extended mesh structure during the "blind" injection process, while also achieving targeted delivery with ca. 20 μm spatial precision. Optical and microcomputed tomography results from injections into tissue-like hydrogel, ex vivo brain tissue, and in vivo brains validate our basic approach and demonstrate its generality. Second, we present a general strategy to achieve up to 100% multichannel I/O connectivity using an automated conductive ink printing methodology to connect the mesh electronics and a flexible flat cable, which serves as the standard "plug-in" interface to measurement electronics. Studies of resistance versus printed line width were used to identify optimal conditions, and moreover, frequency-dependent noise measurements show that the flexible printing process yields values comparable to commercial flip-chip bonding technology. Our results address two key challenges faced by syringe-injectable electronics and thereby pave the way for facile in vivo applications of injectable mesh electronics as a general and powerful tool for long-term mapping and modulation of brain activity in fundamental neuroscience through therapeutic biomedical studies.
具有类似组织机械性能和开放大孔结构的可注射式注射器电子设备是一种新兴的强大范例,可用于映射和调节大脑活动。事实上,这种超灵活的大孔结构在慢性研究中表现出了前所未有的最小/非侵入性和促进与神经元的吸引力相互作用。这些相同的结构特征也为在特定脑区进行精确靶向输送以及为可靠的电测量所需的定量输入/输出(I/O)连接提供了新的挑战和机遇。在这里,我们描述了以灵活的方式解决这两个问题的新结果。首先,我们开发了一种控制注射方法,该方法在“盲目”注射过程中保持扩展的网格结构,同时实现了约 20μm 的空间精度的靶向输送。在类似于组织水凝胶、离体脑组织和体内脑组织中的注射的光学和微计算机断层扫描结果验证了我们的基本方法,并证明了其通用性。其次,我们提出了一种通用策略,使用自动化导电油墨印刷方法来实现高达 100%的多通道 I/O 连接,将网格电子产品和柔性扁平电缆连接起来,作为测量电子产品的标准“插件”接口。对电阻与打印线宽的研究用于确定最佳条件,而且,频率相关噪声测量表明,柔性印刷工艺产生的值可与商业倒装芯片键合技术相媲美。我们的研究结果解决了可注射电子设备所面临的两个关键挑战,从而为可注射网格电子设备作为一种通用且强大的工具在基础神经科学中进行长期映射和调节大脑活动的简便体内应用铺平了道路,通过治疗性生物医学研究。