🥳 30 years since one of the pioneering single-molecule FRET papers transformed biomolecular dynamics research. Join our special seminar with Prof. Taekjip Ha, who made the first smFRET measurement, to explore 3 decades of progress - and what's next. 🔬 us06web.zoom.us/meeting/regi… #smFRET #seminar #singlemolecule #biophysics

🥳 30 years ago, one of the pioneering papers in single-molecule FRET helped transform how we study biomolecular dynamics. To mark this milestone, we're hosting a special Exciting Seminar exploring the evolution of smFRET over the last three decades - and where the field is heading next. We're delighted to be joined by Prof. Taekjip Ha, who made the very first smFRET measurement, to discuss the past, present, and future of the technique. Plus in this month's newsletter: 🔬 New application note on pH-sensitive DNA nanoswitches 📖 Practical guide to FCS/FCCS 🌍 Upcoming events across Europe and the US 🎉 Customer installation success at Technion ❓ Application FAQs Register for the seminar > us06web.zoom.us/meeting/regi… Read the newsletter > excitinginstruments.com/wp-c… Subscribe to the newsletter > share-eu1.hsforms.com/2tB-S9… #smFRET #singlemolecule #biophysics #structuralbiology #fluorescencespectroscopy #birthday

👋 Hands up who's at the Machines on Genes @BiochemSoc conference this week! Roman is looking forward to discussing how our easy-to-use tools allow you to assess the conformational dynamics and interactions of individual molecular machines. Say hello to him if you want to: - unravel the structural dynamics in your favourite molecular machines - understand the molecular mechanisms underlying transcription, replication and genome maintenance - detect when higher-order protein-nucleic acid complexes form 👀 Especially if directly in solution, on your benchtop. Don't miss his talk on Tuesday morning (10:20 am) to learn more about how our platform can help your research. #smFRET #DNArepair #chromatin #crete #machinesongenes #FCS

🐮 What lies between the ‘spherical cow’ of purified proteins and the technical complexity of live cell imaging? While this does sound like the start of a terrible joke, the punchline is something quite Exciting. The compromise between the sterile test tube and the living cell offers a messy middle ground, whereby single-molecule biophysics is performed directly in cell lysates and serum. In our latest article, we discuss how to get the most out of your single-molecule spectroscopy studies, backed up by case studies showing these techniques in action and proving that modern biophysics can thrive with ‘messy’, physiologically relevant samples. Read on for: -    How in-cell labelling and direct analysis of cell lysates can be achieved to preserve native folding and post-translational modification -    The use of alternating laser excitation and background correction to detect proteins of interest through the noise of ‘messy’ samples -    Case studies that exemplify these workflows, from developing a universal protein ladder for FRET, to calculating the binding affinity of antibodies to proteins produced via cell-free expression  Ready to embrace the chaos? > excitinginstruments.com/reso… #biophysics #singlemolecule #incelllabelling

🤔 Interested in performing smFRET experiments but unsure how to label your samples? Or feeling stuck when deciding which dyes you should use? Labelling your samples is a crucial part of any smFRET experiment and can have a profound impact on the resultant data. To support your experimental design, we’ve put together a technical note to guide you through these practical considerations and provided recommended protocols to help you prepare your own samples. 📖 Inside you'll find: •    Discussion of various commercially available dye pairs and ideal characteristics for FRET •    Methods for site-specific labelling for proteins and nucleic acids •    Important considerations that influence how a dye pair may behave in different biomolecular environments or distances from one another Ready to explore labelling strategies for smFRET? Download the technical note here > excitinginstruments.com/reso… #smfret #biophysics #biochemistry #singlemolecule #howto

👀 Does the answer to your scientific question depend on understanding how molecules truly interact in solution? 🙌 Fluorescence Correlation Spectroscopy (FCS) and Fluorescence Cross-Correlation Spectroscopy (FCCS) make these measurements possible, at single-molecule sensitivity and without surface immobilisation. Our new handbook provides a practical introduction to understanding the fundamentals of FCS and FCCS, and their applications in your research. Designed for both newcomers and experienced users looking to apply solution-based single-molecule techniques to their biological systems. 📘 Download the handbook here > excitinginstruments.com/fcs-… #fcs #fccs #fluorescencecorrelationspectroscopy #biophysics #biochemistry

🙌 Yesterday at #smbio26 was a shining example of cutting-edge single-molecule science in the UK, and it was brilliant to see so many talented and inspiring people come together in our hometown, Sheffield. Tim, Roman and Charlotte are on hand for day two to discuss all the Exciting things your molecules are doing, and - importantly - how our technology can help you see this! We're also welcoming guests over to our nearby HQ for demos of our system - if you're interested, just let the team know. 👏 Here's to another brilliant day ahead. #smbio26sheffield #singlemolecule #smfret #fcs

👀 X-ray crystallography provides structures in exquisite atomic detail, but doesn't always capture the whole conformational landscape of a protein. In our most recent application note, produced in collaboration with the Leake lab at the @UniOfYork , we explore how Howard et al. used single-molecule Förster Resonance Energy Transfer (smFRET) and fluorescence correlation spectroscopy (FCS) on the EI-FLEX to reveal two previously unknown, salt-influenced conformational states on the bacterial helicase Rep. In this application note, you'll discover how: • FCS identifies variations in hydrodynamic radius and diffusion time that are likely caused by salt-induced protein conformational changes •smFRET uncovers two conformational states that were not identified in crystal structures, which are influenced by salt concentration and DNA binding •Combining smFRET data with complementary techniques, such as ABEL trapping, resolves multiple interconversion conformational states that persisted on sub-millisecond to second timescales 🙌 Read the full application note here and discover how single-molecule tools can bring your static structures to life > excitinginstruments.com/reso… #biochemistry #singlemolecule #smfret #fcs

Who's heading to #smbio26 this week? We're proud sponsors of the event, plus this year it's being held in our home city - Sheffield 🍃 Catch up with @Craggs_Lab and Roman to discover next-generation single-molecule fluorescence technologies that are helping researchers reveal biomolecular interactions and dynamics with exceptional sensitivity and throughput. Let us know in the comments if you'll be there! #smbio2026sheffield #singlemolecules #sheffie

🤔 Is the ‘average’ molecule a liability in modern drug discovery? In the development of complex biologics and targeted protein degraders (TPDs), traditional bulk assays often provide an incomplete picture. They measure the ensemble average, which masks the real-time conformational changes and transient states that determine whether a candidate succeeds or fails in the clinic. Our latest article explores how single-molecule techniques (smFRET, FCS, and FCCS) are moving from academic niche to biopharma essential. Key takeaways include: •    Mapping IDPs: Resolving the conformational ensembles of ‘undruggable’ disordered proteins. •    TPD characterisation: Using FCCS to directly quantify ternary complex formation and ubiquitination of targets. •    Structural synergy: How single-molecule dynamics complement Cryo-EM’s high-resolution snapshots to bring structures to life. •    Lab-in-the-Loop: Integrating high-fidelity biophysical data into AI-driven discovery cycles. In an era of high-stakes modalities, the ability to resolve individual molecular behaviours is crucial for derisking pipelines and bringing complex therapeutics to the clinic. After all, there are no average molecules. Read the full article here > excitinginstruments.com/reso… #drugdiscovery #biopharma #labintheloop #tpds

🔎 Understanding the molecular mechanism of action of therapeutics, not just the overall impact of their action, is crucial during the drug discovery and development process. Groves et al. developed a doubly labelled RNA hairpin that acts as a reporter for RNA extension by RdRp when analysed using smFRET. They used this, alongside FCS, to investigate the mechanism of action of two viral SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibitors: a nucleotide competitive inhibitor (remdesivir) and a non-nucleotide inhibitor (sumarin). Overview of this application note (produced in collaboration with the Robb Lab at the University of Warwick): • smFRET can distinguish non-extended from extended RNA species and the effect of RNA-dependent RNA polymerase inhibitors on this process • FCS provides further context in the form of identifying RdRp stalling on RNA • These techniques provide complementary data alongside gel-based assays, distinguishing the mechanisms of action for a nucleotide competitive inhibitor and a non-nucleotide inhibitor 👀 Interested in seeing the data? Access the application note here > excitinginstruments.com/reso… #smfret #fcs #RNA #proteinrnainteractions

🇺🇸 Heading to the Industrial Biostructures America #ProterosIBAConference next week? Visit Jake at our Exciting Instruments booth for an introduction to the EI-FLEX Pro! Understanding the conformational populations and dynamics of protein drug targets provides a powerful complement to static structural methods and computational approaches. 🙌 With the EI-FLEX Pro, biopharma labs can now use single-molecule FRET (smFRET) to distinguish individual conformers in solution and quantify biomolecular heterogeneity with ease. With automated setup, microplate compatibility, and intuitive software, the EI-FLEX Pro brings advanced smFRET into everyday drug discovery workflows. See you at the booth! #drugdiscovery #biopharma

🤔 Still wondering how single-molecule FRET works in practice and how it can complement your current techniques? Our practical handbook explains when - and why - smFRET is the method of choice to use alongside your existing methods by adding a layer of dynamic data that can quantify biomolecular conformations and complex formation. Download if you want to: ✓ introduce a simple, solution-based method into your existing workflows that rapidly resolves conformational changes at the single molecule level ✓ complement existing static workflows with dynamic data ✓ unlock deeper functional insights and novel biological questions 📖 > excitinginstruments.com/smfr… #smfret #biophysics #biochemistry #singlemolecul

👋 Do you lead a core facility offering powerful structural techniques like cryo-EM or X-ray crystallography? Many biological systems are dynamic in solution. Techniques like smFRET and FCS complement structural approaches by resolving conformational dynamics, heterogeneity, and interactions in real time. Add a solution-based, single-molecule layer to your facility’s capabilities - and help users connect structure to function. Learn how to complement your structural toolkit with dynamics using the EI-FLEX system: excitinginstruments.com/ei-f… #corefacility #biophysics #biochemistry #singlemolecule

How do we link atomic detail to molecular motion? With 250,000 structures in the Protein Data Bank, we’ve become experts at seeing what proteins look like. However, to truly understand catalysis, signalling, and drug binding, we need to bridge the gap between static coordinates and dynamic ensembles. In our latest article, we explore how single-molecule FRET (smFRET) provides dynamic insights for structures derived from common techniques such as X-ray, Cryo-EM, and AlphaFold predictions. Combining these techniques with smFRET opens a world of discoveries that have traditionally proved challenging: -    Mapping allosteric networks -    Resolving ‘dark’ regions in flexible loops and IDPs -    Identifying cryptic pockets in ‘undruggable’ targets 👀 Read the full article here: excitinginstruments.com/reso… #proteins #moleculardynamics #structuralbiology #smfret

🔬 Studying protein-DNA interactions and wondering how freely-diffusing single-molecule techniques like smFRET and FCS can support your research? Here are a couple of the most commonly asked questions we hear from scientists in this space. Find more frequently asked questions on our protein-DNA application page > excitinginstruments.com/appl… #proteindnainteractions #biophysics #biochemistry #singlemolecule

🙌 Proud to be sponsoring today's London Polymer Group 2026 meeting at @imperialcollege! Look out for Tim and Charlotte, who are ready and waiting to discuss how single-molecule data can complement your existing workflows to reveal polydispersity and polymer conformational dynamics, and confirm nanoparticle cargo loading or leakage in real-time. #LondonPolymerGroup2026 #LPG26 #polymers #singlemolecule