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A label-free optical sensor system on silicon: Determining the thermodynamic and kinetic quantities of protein-ligand interactions

硅上无标记光学传感器系统：确定蛋白质-配体相互作用的热力学和动力学量

基本信息

批准号：
257184830
负责人：
Professor Dr. Klaus Petermann, Ph.D.
金额：
--
依托单位：
Arbeitsgruppe Organische Chemie (AK Rück-Braun)
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2014
资助国家：
德国
起止时间：
2013-12-31 至 2017-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/257184830?language=en
关键词：
label free optical sensor system

项目摘要

Optical label-free biosensors using free-space optics like surface plasmon resonance devices have successfully entered the market. Meanwhile it becomes clear that chip-integrated solutions for optical label-free biosensing feature many advantages like significant size reduction enabling a large number of sensor elements on a small chip, highly parallel operation and a minimal demand of biomaterial. In this proposal a multidisciplinary approach brings together the expertise in silicon photonics, chemistry and biochemistry. The overall goal is to develop a silicon based optical biosensor system for highly parallel assays and the necessary chemistry to get a real world biosensor system for parallel real time measurements of several kinds of biological protein-ligand interactions.The group of Petermann/Bruns brings in their knowledge on silicon photonics, the group of Rück-Braun the expertise on silicon surface chemistry including analysis, and the group of Volkmer brings in the biological models on which the biosensor can be optimized and tested extensively.The sensor itself will be realized in SOI (silicon-on-insulator). We combine well known ring resonators as sensing elements with a new approach for massive parallel sensing based on thermo-optical modulation. To maximize the applicability of the sensor, a new structure for large dynamic sensing will be developed. Furthermore, to achieve the best solution for our applications, several variations of the sensor structure like waveguide type and ring shape will be performed.On the biochemical side, established silicon surface chemistry and well described protein-ligand interactions will be used to functionalize and verify the sensor system.Using microfluidics, parallel quantitative affinity measurements of the biological interactions under investigation will be performed. Temperature dependent measurements will be established to determine the thermodynamic parameters such as Gibbs free energy, enthalpy, entropy and reaction activation energy. Finally, the very challenging determination of the protein-protein interaction stoichiometry will be investigated. We will try to determine the oligomeric state of a protein complex using our label-free biosensor system. This biosensor system will give us the possibility to determine the thermodynamic, kinetic and stoichiometric parameters of protein-ligand interactions with a single experimental run.

使用自由空间光学的光学无标记生物传感器，如表面等离子体共振装置，已成功进入市场。同时，很明显，用于光学无标记生物传感的芯片集成解决方案具有许多优点，如显著的尺寸减小，使大量的传感器元件能够在小芯片上，高度并行操作和最小的生物材料需求。在这项提案中，多学科方法汇集了硅光子学，化学和生物化学方面的专业知识。总体目标是开发一种基于硅的光学生物传感器系统，用于高度并行的分析和必要的化学反应，以获得一个真实的世界生物传感器系统，用于并行真实的时间测量几种生物蛋白质-配体相互作用。Petermann/Bruns小组带来了他们在硅光子学方面的知识，Rück-Braun小组带来了硅表面化学方面的专业知识，包括分析，生物传感器的优化和测试将基于生物模型，传感器本身将在SOI（silicon-on-insulator）中实现。我们结合联合收割机众所周知的环形谐振器作为传感元件的大规模并行传感的热光调制的基础上的新方法。为了最大限度地提高传感器的适用性，将开发一种用于大动态传感的新结构。此外，为了实现最佳的解决方案，我们将对传感器结构进行多种变化，如波导类型和环形。在生物化学方面，将使用已建立的硅表面化学和良好描述的蛋白质-配体相互作用来功能化和验证传感器系统。使用微流体，将对正在研究的生物相互作用进行并行定量亲和力测量。将建立温度依赖性测量以确定热力学参数，例如吉布斯自由能、焓、熵和反应活化能。最后，非常具有挑战性的确定蛋白质-蛋白质相互作用的化学计量将进行研究。我们将尝试使用我们的无标记生物传感器系统来确定蛋白质复合物的寡聚状态。这种生物传感器系统将使我们有可能确定热力学，动力学和化学计量参数的蛋白质配体相互作用与一个单一的实验运行。