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Investigating Complex Samples with Molograms of Low-Affinity Binders
ACS Sensors ( IF 8.9 ) Pub Date : 2021-02-25 , DOI: 10.1021/acssensors.0c02346
Andreas M. Reichmuth 1 , Katharina Kübrich 1 , Yves Blickenstorfer 1 , Andreas Frutiger 1 , Dmitry Momotenko 1 , Volker Gatterdam 1 , Fridolin Treindl 1 , Christof Fattinger 2 , János Vörös 1
Affiliation  

In vitro diagnostics relies on the quantification of minute amounts of a specific biomolecule, called biomarker, from a biological sample. The majority of clinically relevant biomarkers for conditions beyond infectious diseases are detected by means of binding assays, where target biomarkers bind to a solid phase and are detected by biochemical or physical means. Nonspecifically bound biomolecules, the main source of variation in such assays, need to be washed away in a laborious process, restricting the development of widespread point-of-care diagnostics. Here, we show that a diffractometric assay provides a new, label-free possibility to investigate complex samples, such as blood plasma. A coherently arranged sub-micron pattern, that is, a peptide mologram, is created to demonstrate the insensitivity of this diffractometric assay to the unwanted masking effect of nonspecific interactions. In addition, using an array of low-affinity binders, we also demonstrate the feasibility of molecular profiling of blood plasma in real time and show that individual patients can be differentiated based on the binding kinetics of circulating proteins.

中文翻译:

用低亲和力粘合剂的摩尔图研究复杂的样品

体外诊断依赖于对生物样品中微量的特定生物分子(称为生物标志物)的定量。通过结合测定法可检测出大多数传染性疾病以外的临床相关生物标记物,其中靶标生物标记物与固相结合,并通过生化或物理手段进行检测。非特异性结合的生物分子是此类分析方法的主要变化来源,需要在费力的过程中冲洗掉,这限制了广泛的即时诊断的发展。在这里,我们显示了衍射测定法提供了一种新的,无标签的可能性来研究复杂的样本,例如血浆。相干排列的亚微米图案,即肽摩尔图,创建了用于证明该衍射测定法对非特异性相互作用的有害掩盖作用不敏感的化合物。此外,使用一系列低亲和力结合剂,我们还证明了实时进行血浆分子谱分析的可行性,并表明可以根据循环蛋白的结合动力学来区分个别患者。
更新日期:2021-03-26
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