“Ultimately, in the core facility, we see a real broad range of use cases for the EI-FLEX, from basic physics all the way up to biomedicine.” We had the pleasure of sitting down with Alex Payne-Dwyer, Senior Technical Specialist in the Bioscience Technology Facility at the University of York, who shared his experiences of running an EI-FLEX in a core facility. We are also grateful to Facility Director Peter O'Toole for his input in the discussion. 🙌 From training new students in a matter of hours to discussing the EI-FLEX publications that have already emerged from the facility, Alex describes the possibilities that democratised biophysics now brings to the institute and how you can make the most of having an EI-FLEX in your own facility. Read the interview here: excitinginstruments.com/reso… #corefacility #biophysics #singlemolecule #smfret #researchtechnology

Curious to see how Doxsey and Shen used the EI-FLEX to resolve ligand-induced conformational changes in Rag GTPase? Specifically, they collected smFRET measurements across a range of conditions to discern how the global structure of Rag GTPase changes and drives downstream signalling in response to cellular amino acid sensing. Overview of this application note: 🔄 Rag GTPase binding of guanine diphosphate (GDP) and/or guanine triphosphate (GTP) drives global conformational changes that differ depending on the combination of bound nucleotides 🤝 Dual binding of GTP induces inter-subunit cross-talk that stabilises Rag GTPase in order for hydrolysis to occur 🧬 Mutations in the nucleotide-binding domain that hyperactivate or inhibit mTORC signalling can be linked to Rag GTPase structural changes, independent of correct nucleotide binding 🔓 Binding of the mTORC subunit Raptor causes Rag GTPase to adopt an open, bound conformation Ready to see how you could apply these techniques to your own protein-ligand systems? Read the full application now: excitinginstruments.com/reso… #smfret #raggtpase #proteinconformation #proteindynamics

You know your molecules are binding - but do you understand how they interact? In targeted protein degradation, binding affinity is only part of the story. Researchers also need to know whether proteins come together in the right orientation, whether cooperativity exists, and whether those interactions are likely to drive degradation. As therapeutic mechanisms become more sophisticated, our analytical approaches need to evolve alongside them. That's exactly what we'll explore in this week's Exciting Seminar with Dr Stefan Mueller, where he'll demonstrate how fluorescence cross-correlation spectroscopy (FCCS) enables direct characterisation of ternary complexes and higher-order protein interactions. 📅 20th August Register here: us06web.zoom.us/meeting/regi… #drugdiscovery #TPD #targetedproteindegradation #PROTAC #molecularglues #FCCS #singlemolecule

🧬 The biological world exists across energy landscapes, involving transient intermediates, rate-limiting conformational shifts, and complex binding equilibria. In order to derive understanding from this energetic chaos, we have perfected observing biology in snapshots, from frozen or crystalline structures to averaged readouts of our cells fixed in a moment in time. This has provided a wealth of information, but omits a key component of life, from the subcellular to the macroscopic: biology is dynamic. To truly understand these systems, we need to view them as they are, in solution and in motion, observing individual molecules to find the rare intermediates that would otherwise be lost amongst the average. In this article, we explore three techniques (smFRET, FCS, and FCCS) that capture these vital in-solution dynamics, highlighting case studies where these methods revealed mechanistic insights, linking structure to function: 🔄 How smFRET captures the global conformational changes induced by nucleotide binding of Rag GTPase and the allosteric impact of mutations in the nucleotide binding domain 🦠 The use of smFRET and FCS to investigate the mechanism of action of two distinct antiviral drugs against SARS-CoV-2 RNA-dependent RNA polymerase 🔗 How FCCS characterises ternary complex formation and kinetics, from cooperativity to stability Curious to see the data? Access the full article here > excitinginstruments.com/reso… #smfret #fcs #fccs #biophysics #mechanisticinsights #article

👀 Does your compound show excellent binding affinity but still fail as a degrader? That's a common challenge in targeted protein degradation. PROTACs and molecular glues rely on more than target binding. Their success depends on forming a productive ternary complex between the target protein, degrader and E3 ligase. A compound can perform well in binding assays yet fail in cells if binding doesn't translate to degradation. The key question is no longer just whether it binds - it's whether it forms a productive complex. Join our upcoming Exciting Seminar with Dr Stefan Mueller to learn how fluorescence cross-correlation spectroscopy (FCCS) on the EI-FLEX Pro HT enables direct, solution-phase measurement of ternary complex formation and cooperativity. Using HER2-targeting antibodies trastuzumab and pertuzumab as a model system, Stefan will show how FCCS provides molecular insights that can accelerate next-generation therapeutic discovery. 📅 20th August Register here > us06web.zoom.us/meeting/regi… #drugdiscovery #targetedproteindegradation #PROTAC #molecularglues #biophysics #lifesciences #FCCS

"In the past, my team spent more time troubleshooting open source software packages than actually looking at their data." That was the reality for Dr Janice Pata, Director at the Wadsworth Centre, New York State Department of Health. After adopting PhotonFit, she says: "PhotonFit has completely removed that friction. The interface is intuitive, and the sliding scales for real-time parameter tuning give us immediate confidence in our results. It has turned complex, manual analysis into a same-day discovery session, allowing us to focus on the biology instead of the code." This is exactly why we built PhotonFit. Researchers shouldn't have to spend hours stitching together software, troubleshooting scripts, or wrestling with analysis before they can start interpreting their data. PhotonFit brings smFRET, FCS, and FCCS analysis into a single intuitive workspace, making it easier to move from raw photon streams to publication-ready results. Key capabilities include: 🔬 Unified analysis for smFRET, FCS, and FCCS ⚡ Real-time parameter adjustment with instant visual feedback 📊 Side-by-side sample comparison 📈 Publication-ready figures and rapid data export If you'd like to see how PhotonFit - and the wider EI-FLEX platform - can simplify your single-molecule workflow, watch our 90-second walkthrough > youtube.com/watch?v=_8S7KjQi… #smfret #fcs #fccs #singlemolecule #lifesciences #biophysics

Are you trying to characterise higher-order protein complexes, but finding it difficult to quantify their affinity, cooperativity, and kinetic stability directly? Many biological processes and emerging therapeutic modalities - including multispecific antibodies, molecular glues, and targeted protein degraders - depend on higher-order protein complexes whose behaviour cannot be understood from binary interactions alone. Join Dr Stefan Mueller in our upcoming Exciting Seminar, where he will show how fluorescence cross-correlation spectroscopy (FCCS) on the EI-FLEX Pro HT enables direct, solution-phase characterisation of multicomponent protein interactions. Using the HER2-targeting antibodies trastuzumab and pertuzumab as a model system, he will demonstrate how FCCS can quantify binary binding, directly measure ternary complex formation, and reveal cooperative interactions that stabilise the complex - providing new molecular insight into the success of dual HER2-targeted therapies. He'll also explore how this approach can help accelerate the discovery and characterisation of next-generation therapeutics built on higher-order protein assemblies. Join us on the 20th August to see how FCCS is expanding what's possible in ternary complex analysis. Register here > us06web.zoom.us/meeting/regi… #ternarycomplex #fccs #proteininteractions #drugdiscovery

For decades, Surface Plasmon Resonance (SPR) has been the gold standard for real-time kinetic profiling. However, as discovery pipelines focus increasingly on transient, intrinsically disordered, or multi-component assemblies, surface immobilisation can introduce technical bottlenecks. By contrast, solution-phase Fluorescence Cross-Correlation Spectroscopy (FCCS) offers a direct, immobilisation-free alternative. By measuring the co-diffusion of fluorescently labelled binding partners, FCCS delivers absolute measurements of affinity, cooperativity, and dissociation kinetics directly in native solution. Whether you’re looking to validate hits from high-throughput screens or gain more confidence in your degrader candidates as you progress towards cell-based studies, FCCS provides direct proof of ternary complex formation without the need to establish binary kinetics first. Curious to discover how easy direct analysis of ternary complex formation and kinetics can be? Read our new application note to see the data in more detail > excitinginstruments.com/reso… #spr #fccs #ternarycomplex #kinetics

Curious to see smFRET data on ssDNA? In our latest application note, fantastic work from the Antony lab at St Louis University School of Medicine showcases ssDNA smFRET data collected on the EI-FLEX. Here, Chadda et al. clarify conflicting data from crystal structures and bulk methods that failed to reach consensus on whether binding causes DNA wrapping or stretching. Read the application note to discover how: •    End-to-end distances of a variety of ssDNA molecules were calculated from FRET efficiency values, showing linear relationships between number of bases and distance •    Data captured on the EI-FLEX was in good agreement with distances calculated using the Picoquant MT-200 instrument •    A reduction of end-to-end distance of 2.6 Å was observed upon addition of RPA, which was maintained irrespective of ssDNA length, indicating that DNA wraps around RPA, rather than being stretched Interested? Read here > excitinginstruments.com/reso… #appnote #dna #smfret

🙌 Exciting new data from us here at Exciting Instruments HQ! In a brand new preprint, we demonstrate the use of FCCS for solution-phase characterisation of ternary complexes, namely HER2-targeting antibodies trastuzumab and pertuzumab with HER2 itself. Here, these data directly capture the formation of the HER2–trastuzumab–pertuzumab complex, alongside the quantification of binding affinity, cooperativity, and dissociation rates of these ternary complexes - all without needing to establish binary interactions first. 👀 You can read the full preprint here: excitinginstruments.com/reso… Interested in finding out more? Get in touch to explore how you could use FCCS to characterise your own ternary complex systems – all in solution, on the benchtop, and with guided, bespoke workflows designed for all scientists. #fccs #preprint #ternarycomplex

If you work in molecular biology, biophysics, genomics, or biotechnology, this Exciting Seminar is well worth adding to your watch list! In this fascinating seminar, Professor Taekjip Ha explores: 🔬 How single-molecule FRET has transformed our understanding of molecular dynamics 🧬 What we've learned about DNA-processing enzymes and molecular machines ✂️ How these insights are improving CRISPR and Prime Editing technologies 💡 Why understanding biological mechanisms at the single-molecule level is key to developing the next generation of biotech tools One of the biggest takeaways is a simple but powerful idea: When you can watch biology one molecule at a time, you can engineer better solutions. Whether you're already using fluorescence microscopy, interested in genome editing, or simply want to hear from one of the pioneers who helped shape the field, this talk offers a unique blend of scientific history, cutting-edge research, and practical innovation. Grab a coffee, set aside an hour, and discover how single-molecule science continues to influence the future of biotechnology. 📺 youtu.be/w0Idz5AoW4E?si=Ht7A… #singlemolecule #biotechnology #smfret #innovation #biophysics

Heading to the British Biophysical Society and Deutsche Gesellschaft für Biophysik conference in Glasgow this week? Our Dr Roman Renger will be there and is happy to chat about: 🧬 Unravelling the structural dynamics in your favourite biomolecules (proteins, nucleic acids) directly in solution 🧩 Detecting when (higher-order) protein-protein or protein-nucleic acid complexes form 💡The possibilities of single-molecule FRET and Fluorescence Correlation Spectroscopy in your own research Don't miss his talk on Wednesday afternoon (3:30pm) to learn more about how our platform can help your research. If you would like to have a conversation, please let Roman know via [email protected], visit him at our booth or check out our poster in Poster Session 2B on Wednesday, 15 July. See you there! #DGfB #BBS #biophysics #smfret #fcs

📢 Today's the day! Join Tim Craggs and Prof. Taekjip Ha in this afternoon's Exciting Seminar. • Share in the celebration of 30 years of smFRET, hearing directly from the scientist behind the first smFRET measurement • Feel inspired by what's possible - see how one pioneering discovery evolved into technologies transforming biology today • Be part of a milestone and feel connected to a defining moment in the history of single-molecule science • Leave with excitement about where smFRET and related technologies are heading next • Step away from the day-to-day and remember how fundamental discoveries can lead to world-changing innovations We hope to see you there. Register here > us06web.zoom.us/meeting/regi… #biophysics #smfret #singlemolecule #virtualevent

🔬Cell-free expression of proteins offers a wide range of benefits, from speed and ease to high control over the reaction conditions. Real-time quantification of protein concentration can be measured using FCS in a purification-free method, as demonstrated in new data from Laurence et al. from the Lawrence Livermore National Laboratory. In an application note produced in collaboration with the authors, we demonstrate how FCS was performed on the EI-FLEX to characterise cell-free protein synthesis of YFP-CopB, a fusion of Chlamydia Outer Protein (Cop) B and Yellow Fluorescent Protein (YFP). Key messages from this work: • Cell-free synthesis of the YFP-CopB fusion protein was measured using FCS on the EI-FLEX over a 10-hour period • Calculation of the confocal volume was performed using Cy3B, a common dye with a known diffusion coefficient • Autofluorescence of the cell-free lysate can be distinguished from the photons emitted by the YFP-CopB fusion protein under 520 nm laser excitation Interested in seeing how you could apply FCS to quantify protein production in your own cell-free systems? Access the application note and preprint on our website now > excitinginstruments.com/reso…

📢 Upcoming Exciting Seminar | Conformational control: From single molecule FRET to novel biotechnologies 🗓️ 13th July | Virtual ⏱️ 11:00am EDT | 8:00am PDT | 4:00pm BST | 5:00pm CEST Explore the past, present and future capabilities of single-molecule FRET with our CEO and founder, Tim, and Prof. Taekjip Ha, who made the first ever smFRET measurement 30 years ago. His talk will cover smFRET to next-generation genome engineering and imaging technologies. Check out the abstract for his presentation in the newsletter here > linkedin.com/pulse/upcoming-… Register now 🔗 us06web.zoom.us/meeting/regi… #smfret #singlemoleculefret #biophysics #webinar #seminar