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.

聚焦胶相成像技术是下一代生物传感器，可实时可视化特定的生物分子相互作用。它将传感器表面的亲和力调制转换为由目标分子引起的折射率调制，这些目标分子与精确识别的分子识别位点的纳米图案结合，称为“分子图”。对分子图进行设计，以使激光在特定结合的分子处散射，并通过相长干涉在分子图的焦点处生成一个强信号，而在非特定结合的分子处的散射则不起作用。我们介绍了在光敏整体接枝共聚物层上通过亚微米级近场反应性浸没式光刻技术在芯片上实现摩尔图。我们展示了对生物分子的选择性和灵敏检测，在各种复杂的生物样品中，它们与分子图的识别位点结合。这无需复杂的样品制备即可对复杂的生物样品中的非共价相互作用进行无标签分析，并为执行和开发用于诊断测试的免疫分析提供了节省时间和成本的新颖方法。