2025 Label-Free Single Molecule Sensing Gordon Research Conference - Project Summary The ability to precisely detect biomolecules and measure their dynamics is central to our understanding of the origins of debilitating diseases such as Alzheimer’s and Parkinson’s and is a prerequisite for designing more effective treatments. However, biomolecules are typically a few nanometers in size, which makes them difficult to observe with optical methods. One of the primary ways to overcome this challenge is to add labels, such as fluorescent tags, that make them visible. This has opened the field of single molecule analysis, with the significant advantages of allowing rare events to be observed, solution heterogeneity to be understood, and molecular dynamics to be monitored without synchronization of molecular dynamics in an ensemble. At the same time, chemical tag or genetic modifications can alter a biomolecule’s function and how it interacts with its environment. Furthermore, fluorescent labels have limited lifetime (photobleaching), time-resolution (finite fluorescence lifetime) and require additional assay preparation steps that are time-consuming and costly. Given that this area of research is wide open for exploration, we believe that there is room for knowledge exchange and augmenting technologies that will evolve into a set of techniques that will become the new standard within academia, pharmaceutical industry alike. The aim of this inaugural Gordon Research Conference (GRC) is to maximize the exchange of ideas among these techniques, look at their common issues and solutions, and help with commercialization efforts so that the world can see their benefits faster. Specifically, we propose to implement the organization of this inaugural GRC through the following Specific Aims: (Aim 1) To create the first-ever forum that brings together the top scientists from across the globe in the field of label-free biomolecule sensing technologies, and (Aim 2) To educate and inspire the next generation of scientists that will move this field further, paying particular attention to creating opportunities for historically underrepresented students and postdocs. Through implementation of these Specific Aims, this 2025 GRC will bring together a broadly multidisciplinary community, including nanotechnology, plasmonics, biophysics, biochemistry, and biology to create new label- free technologies of single molecule sensors. Rather than focusing on applications, it will be focused on technology – how do you build new kinds of label-free single molecule sensors, and how do you improve their performance far beyond the state-of-the-art. We have also taken many steps to create a welcoming, inclusive community that removes barriers for historically underrepresented groups, women scientists, early career researchers and minorities. Data on trainee participation and feedback on how their participation helped their career post-conference will also be collected to ensure the long-term sustainability and impact of this new GRC.