Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, the Netherlands.
Nat Commun. 2022 Oct 13;13(1):6052. doi: 10.1038/s41467-022-33487-3.
There is a need for sensing technologies that can continuously monitor concentration levels of critical biomolecules in applications such as patient care, fundamental biological research, biotechnology and food industry, as well as the environment. However, it is fundamentally difficult to develop measurement technologies that are not only sensitive and specific, but also allow monitoring over a broad concentration range and over long timespans. Here we describe a continuous biomolecular sensing methodology based on the free diffusion of biofunctionalized particles hovering over a sensor surface. The method records digital events due to single-molecule interactions and enables biomarker monitoring at picomolar to micromolar concentrations without consuming any reagents. We demonstrate the affinity-based sensing methodology for DNA-based sandwich and competition assays, and for an antibody-based cortisol assay. Additionally, the sensor can be dried, facilitating storage over weeks while maintaining its sensitivity. We foresee that this will enable the development of continuous monitoring sensors for applications in fundamental research, for studies on organs on a chip, for the monitoring of patients in critical care, and for the monitoring of industrial processes and bioreactors as well as ecological systems.
需要能够持续监测关键生物分子浓度的传感技术,这些技术可应用于患者护理、基础生物学研究、生物技术和食品工业以及环境等领域。然而,开发不仅敏感、特异,而且还能够在宽浓度范围和长时间内进行监测的测量技术在根本上具有挑战性。在这里,我们描述了一种基于在传感器表面上方悬停的生物功能化颗粒的自由扩散的连续生物分子感测方法。该方法记录由于单分子相互作用而产生的数字事件,并能够在皮摩尔到微摩尔浓度范围内进行生物标志物监测,而无需消耗任何试剂。我们展示了基于 DNA 的夹心和竞争测定以及基于抗体的皮质醇测定的基于亲和力的感测方法。此外,该传感器可干燥,便于在数周内储存,同时保持其灵敏度。我们预计,这将能够开发用于基础研究、器官芯片研究、重症监护患者监测、工业过程和生物反应器以及生态系统监测的连续监测传感器。