Zhao Chuanzhen, Cheung Kevin M, Huang I-Wen, Yang Hongyan, Nakatsuka Nako, Liu Wenfei, Cao Yan, Man Tianxing, Weiss Paul S, Monbouquette Harold G, Andrews Anne M
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Sci Adv. 2021 Nov 26;7(48):eabj7422. doi: 10.1126/sciadv.abj7422. Epub 2021 Nov 24.
While tools for monitoring in vivo electrophysiology have been extensively developed, neurochemical recording technologies remain limited. Nevertheless, chemical communication via neurotransmitters plays central roles in brain information processing. We developed implantable aptamer–field-effect transistor (FET) neuroprobes for monitoring neurotransmitters. Neuroprobes were fabricated using high-throughput microelectromechanical system (MEMS) technologies, where 150 probes with shanks of either 150- or 50-μm widths and thicknesses were fabricated on 4-inch Si wafers. Nanoscale FETs with ultrathin (~3 to 4 nm) InO semiconductor films were prepared using sol-gel processing. The InO surfaces were coupled with synthetic oligonucleotide receptors (aptamers) to recognize and to detect the neurotransmitter serotonin. Aptamer-FET neuroprobes enabled femtomolar serotonin detection limits in brain tissue with minimal biofouling. Stimulated serotonin release was detected in vivo. This study opens opportunities for integrated neural activity recordings at high spatiotemporal resolution by combining these aptamer-FET sensors with other types of Si-based implantable probes to advance our understanding of brain function.
虽然用于监测体内电生理学的工具已经得到了广泛开发,但神经化学记录技术仍然有限。然而,通过神经递质进行的化学通讯在大脑信息处理中起着核心作用。我们开发了用于监测神经递质的可植入适体 - 场效应晶体管(FET)神经探针。神经探针是使用高通量微机电系统(MEMS)技术制造的,在4英寸硅片上制造了150根探针,其柄的宽度和厚度分别为150μm或50μm。使用溶胶 - 凝胶工艺制备了具有超薄(约3至4nm)氧化铟半导体薄膜的纳米级FET。将氧化铟表面与合成寡核苷酸受体(适体)偶联,以识别和检测神经递质血清素。适体 - FET神经探针能够在脑组织中实现飞摩尔级血清素检测限,且生物污染最小。在体内检测到了刺激引起的血清素释放。这项研究通过将这些适体 - FET传感器与其他类型的基于硅的可植入探针相结合,为以高时空分辨率进行综合神经活动记录提供了机会,从而增进我们对脑功能的理解。