Laboratory for Sensors, Department of Microsystems Engineering - IMTEK, University of Freiburg, Germany.
Laboratory for Sensors, Department of Microsystems Engineering - IMTEK, University of Freiburg, Germany.
Biosens Bioelectron. 2014 Nov 15;61:192-9. doi: 10.1016/j.bios.2014.05.014. Epub 2014 May 14.
We present a flexible microsensor, based on a polymer substrate, for multiparametric, electrochemical in vivo monitoring. The sensor strip with a microelectrode array at the tip was designed for insertion into tissue, for fast and localized online monitoring of physiological parameters. The microsystem fabrication on a wafer-level is based on a polyimide substrate and includes the patterning of platinum microelectrodes as well as epoxy and dry-film-resist insulation in a cost-effective thin-film and laminate process. A stable, electrodeposited silver/silver chloride reference electrode on-chip and a perm-selective membrane as an efficient interference rejection scheme are integrated on a wafer-level. Amperometric, electrochemical, enzyme-based biosensors for the neurotransmitter L-glutamate and the energy metabolite L-lactate have been developed. Hydrogel membranes or direct cross-linking as stable concepts for the enzyme immobilization are shown. Sensor performance including high selectivity, tailoring of sensitivity and long-term stability is discussed. For glutamate, a high sensitivity of 2.16 nAmm(-2) µM(-1) was found. For lactate, a variation in sensitivity between 2.6 and 32 nAmm(-2)mM(-1) was achieved by different membrane compositions. The in vivo application in an animal model is demonstrated by glutamate measurements in the brain of rats. Local glutamate alterations in the micromolar range and in nanoliter-range volumes can be detected and quantified with high reproducibility and temporal resolution. A novel, versatile platform for the integration of various electrochemical sensors on a small, flexible sensor strip for a variety of in vivo applications is presented.
我们提出了一种基于聚合物基底的灵活微传感器，用于多参数、电化学的体内监测。传感器带有尖端微电极阵列的条带被设计用于插入组织中，用于快速和局部在线监测生理参数。基于聚酰亚胺基底的晶片级微系统制造包括铂微电极的图案化以及在具有成本效益的薄膜和层压工艺中的环氧树脂和干膜抗蚀剂绝缘。在晶片级上集成了稳定的、电沉积的银/氯化银参比电极和作为有效干扰抑制方案的选择透过性膜。已经开发了用于神经递质 L-谷氨酸和能量代谢物 L-乳酸的安培、电化学、基于酶的生物传感器。展示了水凝胶膜或稳定的酶固定化的直接交联作为稳定的概念。讨论了传感器性能，包括高选择性、灵敏度调整和长期稳定性。对于谷氨酸，发现了 2.16 nAmm(-2) µM(-1)的高灵敏度。对于乳酸，通过不同的膜组成可以实现 2.6 到 32 nAmm(-2)mM(-1)之间的灵敏度变化。通过在大鼠的大脑中进行谷氨酸测量，展示了其在动物模型中的体内应用。可以以高重现性和时间分辨率检测和定量微摩尔范围内和纳升范围内的局部谷氨酸变化。提出了一种新颖的、通用的平台，用于在小型、灵活的传感器条带上集成各种电化学传感器，用于各种体内应用。
