It is challenging to tune the response of biosensors to a set of ligands, for example, cross-reactivity to a given target family while maintaining high specificity against interferents, due to the lack of suitable bioreceptors. We present a novel approach for controlling the cross-reactivity of biosensors by employing defined mixtures of aptamers that have differing binding properties. As a demonstration, we develop assays for the specific detection of a family of illicit designer drugs, the synthetic cathinones, with customized responses to each target ligand and interferent. We first use a colorimetric dye-displacement assay to show that the binding spectra of dual-aptamer mixtures can be tuned by altering the molar ratio of these bioreceptors. Optimized assays achieve broad detection of synthetic cathinones with minimal response toward interferents and generally demonstrate better sensing performance than assays utilizing either aptamer alone. The generality of this strategy is demonstrated with a dual-aptamer electrochemical sensor. Our approach enables customization of biosensor responsiveness to an extent that has yet to be achieved through any previously reported aptamer engineering techniques such as sequence mutation or truncation. Since multiple aptamers for the designated target family can routinely be identified via high-throughput sequencing, we believe our strategy offers a generally applicable method for generating near-ideal aptamer biosensors for various analytical applications, including medical diagnostics, environmental monitoring, and drug detection.

中文翻译：

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使用适体混合物调节生物传感器交叉反应性。

由于缺乏合适的生物受体，调整生物传感器对一组配体的响应（例如与给定目标家族的交叉反应性，同时保持针对干扰物的高特异性）具有挑战性。我们提出了一种通过采用具有不同结合特性的特定适体混合物来控制生物传感器交叉反应性的新方法。作为演示，我们开发了用于特异性检测一系列非法设计药物（合成卡西酮）的检测方法，并对每种目标配体和干扰物进行定制响应。我们首先使用比色染料置换测定来证明双适体混合物的结合光谱可以通过改变这些生物受体的摩尔比来调节。优化的测定可实现合成卡西酮的广泛检测，同时对干扰物的反应最小，并且通常表现出比单独使用任一适体的测定更好的传感性能。该策略的通用性通过双适体电化学传感器得到了证明。我们的方法使得生物传​​感器响应能力的定制达到了通过任何先前报道的适体工程技术（例如序列突变或截断）尚未实现的程度。由于指定目标家族的多个适体通常可以通过高通量测序来鉴定，因此我们相信我们的策略提供了一种普遍适用的方法，用于生成近乎理想的适体生物传感器，用于各种分析应用，包括医疗诊断、环境监测和药物检测。