Laboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, ETH Zurich, 8092 Zurich, Switzerland.
Roche Diagnostics GmbH, 82377 Penzberg, Germany.
Nat Nanotechnol. 2017 Nov;12(11):1089-1095. doi: 10.1038/nnano.2017.168. Epub 2017 Sep 25.
Focal molography is a next-generation biosensor that visualizes specific biomolecular interactions in real time. It transduces affinity modulation on the sensor surface into refractive index modulation caused by target molecules that are bound to a precisely assembled nanopattern of molecular recognition sites, termed the 'mologram'. The mologram is designed so that laser light is scattered at specifically bound molecules, generating a strong signal in the focus of the mologram via constructive interference, while scattering at nonspecifically bound molecules does not contribute to the effect. We present the realization of molograms on a chip by submicrometre near-field reactive immersion lithography on a light-sensitive monolithic graft copolymer layer. We demonstrate the selective and sensitive detection of biomolecules, which bind to the recognition sites of the mologram in various complex biological samples. This allows the label-free analysis of non-covalent interactions in complex biological samples, without a need for extensive sample preparation, and enables novel time- and cost-saving ways of performing and developing immunoassays for diagnostic tests.
焦点分子光谱学是一种下一代生物传感器，可实时可视化特定的生物分子相互作用。它将传感器表面上的亲和力调制转换为目标分子结合到精确组装的分子识别位点纳米图案（称为“分子光谱”）引起的折射率调制。分子光谱的设计方式使得激光在特定结合的分子上散射，通过相长干涉在分子光谱的焦点处产生强信号，而在非特异性结合的分子上散射则不会产生影响。我们通过在光敏整体接枝共聚物层上进行亚微米近场反应性浸入光刻来实现芯片上的分子光谱。我们证明了在各种复杂生物样品中对与分子光谱的识别位点结合的生物分子的选择性和灵敏检测。这允许对复杂生物样品中的非共价相互作用进行无标记分析，而无需进行广泛的样品制备，并为诊断测试的免疫分析提供了新颖的省时和节省成本的方法。
