Engineering biosensors with extended, narrowed, or arbitrarily edited dynamic range.
Engineering biosensors with extended, narrowed, or arbitrarily edited dynamic range.
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DOI：
10.1021/ja209850j
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发表时间：
2012-02-15
影响因子：
15
通讯作者：
Plaxco, Kevin W.
中科院分区：
文献类型：
--
作者：
Vallee-Belisle, Alexis;Ricci, Francesco;Plaxco, Kevin W.
生物分子识别长期以来一直是人工传感技术的重要主题。然而，基于蛋白质和核酸的识别的当前限制是，单位点结合的有用动态范围通常跨越靶浓度的81倍变化，这一效应限制了生物传感器在要求高灵敏度（靶浓度和输出信号之间的更陡峭的关系）或要求更宽范围浓度的定量的应用中的效用。作为回应，我们已经调整了自然界采用的策略来调节其生物识别系统的输入-输出响应，以合理地编辑人工生物传感器的有用动态范围。通过设计一种结构转换机制，我们首先产生了一组表现出相似特异性的受体变体，但跨越了广泛的靶亲和力。然后，我们合理地组合这些变体的子集，以将我们的生物传感器的伪对数线性动态范围扩展到六个数量级。使用其他变体的组合，我们还制造了更精细的三态剂量响应传感器，仅当目标浓度福尔斯下降到高于或低于一些明确定义的中间状态时才敏感地响应。最后，通过结合信号和非信号受体变体，我们成功地将我们的生物传感器的动态范围压缩了一个数量级，并合理地调整了其对任何任意选择的目标浓度的窄阈值响应。鉴于它们在自然界中的广泛存在，这些相同的方法似乎可以显着提高许多基于生物分子的技术的性能。
Biomolecular recognition has long been an important theme in artificial sensing technologies. A current limitation of protein- and nucleic acid-based recognition, however, is that the useful dynamic range of single-site binding typically spans an 81-fold change in target concentration, an effect that limits the utility of biosensors in applications calling for either great sensitivity (a steeper relationship between target concentration and output signal) or for the quantification of more wide-ranging concentrations. In response, we have adapted strategies employed by nature to modulate the input-output response of its biorecognition systems to rationally edit the useful dynamic range of an artificial biosensor. By engineering a structure-switching mechanism, we first generated a set of receptor variants displaying similar specificity, but spanning a wide range of target affinities. We then rationally combined sub-sets of these variants to expand the pseudo-log-linear dynamic range of our biosensor to six orders of magnitude. Using other combinations of variants we have also fabricated more elaborate, three-state dose-response sensors that respond sensitively only when the target concentration falls above or below some well-defined intermediate regime. Finally, by combining signaling and non-signaling receptor variants, we have succeeded in both compressing the dynamic range of our biosensor by an order of magnitude, and in rationally tuning its narrowed threshold response to any arbitrarily selected target concentrations. Given their widespread occurrence in nature, it would appear that these same approaches could significantly enhance the performance of many biomolecule-based technologies.
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