Two decades have passed since the development of the first calcium indicator based on the green fluorescent protein (GFP) and the principle of Förster resonance energy transfer (FRET). During this period, researchers have advanced many novel ideas for the improvement of such genetically encoded FRET biosensors, which have allowed them to expand their targets from small molecules to signaling proteins and physicochemical properties. Although the merits of "genetically encoded" FRET biosensors became clear once various cell lines were established and several transgenic organisms were generated, the road to these developments was not necessarily a smooth one. Moreover, even today the development of new FRET biosensors remains a very labor-intensive, trial-and-error process. Therefore, at this junction, it may be worthwhile to summarize the progress of the FRET biosensor and discuss the future direction of its development and application.Key words: FRET, biosensor, fluorescent protein.

中文翻译：

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基于福斯特共振能量转移的两个十年的遗传编码生物传感器。

自第一个基于绿色荧光蛋白（GFP）和Förster共振能量转移原理（FRET）的钙指示剂开发以来已经过去了二十年。在此期间，研究人员提出了许多改进此类遗传编码FRET生物传感器的新颖思路，从而使他们能够将靶标从小分子扩展到信号蛋白和理化特性。尽管一旦建立了多种细胞系并产生了几种转基因生物，“遗传编码的” FRET生物传感器的优点就变得清晰起来，但这些发展的道路并不一定是一条平坦的道路。而且，即使在今天，新的FRET生物传感器的开发仍然是一个劳动密集型，反复试验的过程。因此，在这个路口，