Investigating the binding interaction of small molecules to large ligands is a compelling task for the field of drug development, as well as agro-biotechnology, since a common trait of drugs and toxins is often a low molecular weight (MW). Here, we improve the limit of detection of the Interferometric Reflectance Imaging Sensor (IRIS), a label-free, highly multiplexed biosensor, to perform small-molecule screening. In this work, characterization of small molecules binding to immobilized probes in a microarray format is demonstrated, with a limit of detection of 1 pg/mm² in mass density. First, as a proof of concept to show the impact of spatial and temporal averaging on the system noise, detection of biotin (MW = 244.3 Da) binding to a streptavidin-functionalized chip is performed and the parameters are tuned to achieve maximum signal-to-noise ratio (SNR ≈ 34). The optimized system is then applied to the screening of a 20-multiplexed antibody chip against fumonisin B1 (MW = 721.8 Da), a mycotoxin found in cereal grains. The simultaneously recorded binding curves yield an SNR ≈ 8. Five out of twenty antibodies are also screened against the toxin in a lateral flow assay, obtaining consistent results. With the demonstrated noise characteristics, further sensitivity improvements are expected with the advancement of camera sensor technology.

中文翻译：

---

高度多路复用的无标记成像传感器，可准确定量小分子结合动力学

由于药物和毒素的共同特征通常是低分子量（MW），因此研究小分子与大配体的结合相互作用是药物开发以及农业生物技术领域的一项重要任务。在这里，我们提高了干涉反射成像传感器（IRIS）（一种无标签，高度复用的生物传感器）的检测极限，以进行小分子筛选。在这项工作中，证明了以微阵列形式结合固定探针的小分子的表征，检出限为1 pg / mm ²质量密度 首先，作为概念验证以显示时空平均对系统噪声的影响，执行了与链霉亲和素功能化芯片结合的生物素（MW = 244.3 Da）的检测，并调整了参数以实现最大的信号转导。噪声比（SNR≈34）。然后将优化的系统应用于针对葡萄球菌素B1（分子量= 721.8 Da）（一种谷物中发现的霉菌毒素）的20多重抗体芯片的筛选。同时记录的结合曲线产生SNR≈8。在侧向流动分析中，还针对毒素筛选了二十种抗体中的五种，获得了一致的结果。凭借已证明的噪声特性，随着相机传感器技术的发展，有望进一步提高灵敏度。