Advanced Microscopy Methods

🔬✨ Revolutionizing Fluorescence Microscopy with Physics-Informed Neural Networks ✨🔬 Thrilled to share the innovative work by Zitong Ye, Yuran Huang, Jinfeng Zhang, Yunbo Chen, Hanchu Ye, Cheng Ji, Luhong Jin, Yanhong Gan, Yile Sun, Wenli Tao, Yubing Han, Xu Liu, Youhua Chen, Cuifang Kuang, and Wenjie Liu! Their study introduces a Physics-Informed Sparse Neural Network (DPS) that significantly extends the resolution of fluorescence microscopy while maintaining high fidelity. 📈 Why it matters: Traditional super-resolution microscopy often faces trade-offs between spatial resolution, imaging depth, and universality. This groundbreaking DPS framework seamlessly integrates deep learning with physics-based imaging models to overcome these limitations. Here are the key takeaways: ✅ Universal Application: A single training dataset enables application across multiple imaging modalities (SIM, confocal, STED). ✅ High Fidelity: Achieved ~1.67x resolution enhancement with precise structural integrity, even in low-signal scenarios. ✅ Efficiency: No need for ground-truth datasets, fine-tuning, or hardware modifications. ✅ Biological Insights: DPS unveiled previously unseen details in biological structures like microtubules, mitochondria, and nuclear pore complexes. 💡 Innovation: The DPS framework employs a synergistic approach, integrating sparsity constraints, forward optics models, and a novel Res-U-DBPN architecture. This design ensures both structural fidelity and computational efficiency. 📖 Explore the research: Check out their publication: https://lnkd.in/duVed2nK Source code is available on GitHub: https://lnkd.in/dFxE7WHs. Let’s discuss—how do you envision physics-informed AI shaping the future of imaging and microscopy? 🚀 #PhysicsInformedNeuralNetworks #FluorescenceMicroscopy #SuperResolution #DeepLearning #BiomedicalInnovation

Quantum Sensors Enable a Revolutionary New Type of Microscopy Overview Researchers at the Technical University of Munich (TUM) have developed nuclear spin microscopy, a groundbreaking imaging technique that leverages quantum sensors to visualize magnetic signals at an unprecedented microscopic scale. This new approach, published in Nature Communications, enables high-resolution optical imaging of nuclear magnetic resonance (NMR) signals, expanding the capabilities of traditional magnetic resonance imaging (MRI). How It Works • The method uses quantum sensors to convert magnetic resonance signals into optical signals, which are then captured by a camera to produce images. • A diamond chip serves as the quantum sensor, detecting nuclear spin interactions at extremely high resolution. • The technique achieves a resolution of ten-millionths of a meter, fine enough to visualize cellular structures—a level of detail previously unattainable with conventional MRI technology. Implications for Science and Medicine This breakthrough could revolutionize biomedical imaging, allowing researchers to study cellular processes, diseases, and molecular interactions with unprecedented precision. Beyond medicine, nuclear spin microscopy may have applications in materials science, quantum computing research, and nanoscale engineering. As quantum technology advances, this novel microscopy technique could unlock entirely new possibilities for imaging and diagnostics at the atomic and molecular level.

🔬 Field Emission Scanning Electron Microscopy (FESEM): Seeing Materials Beyond the Microscale In materials science and catalysis research, understanding surface morphology, particle size, and textural features is just as important as knowing chemical composition. Field Emission Scanning Electron Microscopy (FESEM) is a powerful characterization technique that enables high-resolution imaging at the nanometer scale, providing insights that conventional SEM often cannot. 🔹 What makes FESEM special? FESEM uses a field emission gun (FEG) as an electron source, which produces a highly coherent and focused electron beam. This results in: • Higher spatial resolution (down to ~1–2 nm) • Improved image clarity at low accelerating voltages • Minimal beam damage, especially for sensitive materials 🔹 Working principle (in brief): A focused electron beam scans the sample surface, and the interaction of electrons with surface atoms generates: • Secondary electrons (SE): Reveal surface morphology and topography • Backscattered electrons (BSE): Provide compositional contrast (atomic number dependent) The emitted signals are collected and converted into high-resolution images, allowing detailed surface analysis. 🔹 Why FESEM is crucial in catalyst and zeolite research: FESEM plays a vital role in understanding: ✔ Particle size and shape distribution ✔ Surface roughness and crystal habit ✔ Agglomeration and dispersion of active phases ✔ Structural integrity after modification, calcination, or reaction For ZSM-5 and modified zeolites, FESEM helps correlate morphology changes with catalytic performance, diffusion behavior, and selectivity (e.g., in toluene methylation or shape-selective catalysis). 🔹 FESEM + EDX = Structural + Elemental Insight When coupled with Energy Dispersive X-ray (EDX) analysis, FESEM enables: • Elemental composition analysis • Spatial distribution of modifiers (Mg, Ca, B, P, etc.) • Verification of successful ion exchange or impregnation 🔹 Key advantages of FESEM: ✔ Ultra-high resolution imaging ✔ Excellent depth of field ✔ Low-voltage operation for non-conductive samples ✔ Ideal for nanomaterials, catalysts, polymers, and thin films 🔹 Limitations to keep in mind: ⚠ Requires high vacuum ⚠ Non-conductive samples often need coating (Au/Pt/C) ⚠ Provides surface information only (not bulk structure) 🔬 In summary: FESEM is not just an imaging tool—it is a bridge between structure and performance. Whether you are designing advanced catalysts, studying morphology–activity relationships, or validating material synthesis, FESEM remains an indispensable technique in modern research. 📌 “If you can see it clearly, you can understand it better—and FESEM helps us do exactly that.” Happy learning! Warm regards Kanchan Guru DST INSPIRE Fellow || SRF Manipal University Jaipur #FESEM #EDX #morphology #electron #research #researcher #phd #career

🚨 New Publication from Our Lab 🚨 "A New Method for Cancer Pathology in 3D – No Staining, No Sectioning!" 🧾 Revealing 3D microanatomical structures of unlabeled thick cancer tissues using holotomography and virtual H&E staining Now published in Nature Communications 📣 Traditional histopathology relies on thin, stained 2D tissue sections viewed under a microscope. But this method is inherently limited—it misses the full 3D architecture of tissues, introduces irreversible damage during sectioning, and is both time- and labor-intensive. In this study, we present a novel approach that combines holotomography (label-free 3D imaging) with deep learning-based virtual H&E staining to visualize cancer tissues up to 50 μm thick—without any slicing or chemical staining. 🧠 Why is this important? Preserve tissue integrity for analysis without physical damage Reconstruct entire pathology slides in 3D Enable more quantitative analysis than traditional staining Compatible with advanced techniques like spatial transcriptomics This method unlocks new potential for cancer diagnostics, immunotherapy response prediction, and collaborative multicenter research. We believe this is a transformative step toward computational, quantitative, and truly 3D pathology. ▶ Read the paper: https://lnkd.in/g5jhG9v3 ▶ Collaborating institutions: Biomedical Optics Lab @ KAIST, Prof. Tae Hyun Hwang’s Group (VUMC, formerly Mayo Clinic), TOMOCUBE, Gangnam Severance Hospital (Dr. Su-Jin Shin, Dr. Nam Hoon Cho) ▶ For technology inquiries: www.tomocube.com 📌 "AI + Holotomography = A New Method for 3D Digital Pathology." #3DPathology #VirtualStaining #Holotomography #AIinMedicine #CancerResearch #Tomocube #KAIST #DeepLearningPathology #DigitalPathology #PrecisionMedicine

Three-photon imaging is opening a new window into the living brain. To truly move the Parkinson’s and neurodegenerative disease field forward, we need tools that let us see what was previously invisible. Three-photon microscopy or 3PM is one of those potentially transformative technologies. By reaching deep into brain circuits without disrupting them, 3PM may help us better understand disease mechanisms and speed the path to new therapies. Robert Prevedel and colleagues bring us up to speed in their latest Nature Reviews Neuroscience paper. Key Points: - 3PM enables minimally invasive, high-resolution imaging of deep cortical and subcortical structures, overcoming the depth limits of two-photon microscopy. - The technology has already revealed new insights into neural circuits, glial biology, tumor invasion and immune responses in previously inaccessible brain regions. - Advances in adaptive optics, laser design, and AI-based image restoration are rapidly improving imaging depth, speed and quality. My take: We interviewed Ed Boyden for our new book and I was struck by his comments about building the tools we need to get to the next level. Here are 5 points that resonated w/ me about this article and approach. 1- Deep brain access matters because many key Parkinson’s circuits lie far below the surface. 2- Better imaging tools can help us track changes in neurons, glia and blood vessels in real time 3- Three-photon imaging allows us to study disease processes w/o invasive surgery that alters brain function. 4- These advances could lead to earlier diagnosis, better biomarkers and improved treatment strategies 5- Investment in cutting-edge tools like 3PM will be essential to unlock the next era of discovery for Parkinson’s and all neurodegenerative diseases. https://lnkd.in/ezWrSS_b Parkinson's Foundation Society for Neuroscience Springer Nature Norman Fixel Institute for Neurological Diseases

Scientists have captured real images of molecules using powerful quantum microscopes, allowing us to see structures that were once completely invisible to human eyes. For decades, molecules were only shown as drawings in textbooks. Scientists knew their shapes from calculations and experiments, but they could not actually see them directly. With modern quantum microscopes, that has changed. These tools are so sensitive that they can detect the position of individual atoms inside a molecule. The blurry images you see are not ordinary photographs. They are created using extremely precise scanning techniques that measure how electrons behave around atoms. By scanning the surface point by point, the microscope builds a map of the molecule’s structure. The clearer diagrams next to the images help show what scientists believe the real atomic arrangement looks like. This technology helps researchers study chemistry in ways that were impossible before. They can watch how molecules bond, how reactions begin, and how tiny changes in structure affect materials. These insights help scientists design better medicines, stronger materials, and more efficient electronics. Seeing molecules directly also reminds us how small the building blocks of nature really are. Everything around us, from the air we breathe to the devices we use, is built from these tiny structures. Yet they are so small that billions could fit across the width of a human hair. Quantum microscopes are opening a new window into this hidden world. As the technology improves, scientists will be able to observe even more complex molecules and reactions. Each new image brings us closer to understanding how matter works at its most fundamental level.

Microscopes that are designed to image reflective objects work differently than those used for viewing biological specimens. Rather than shining light through a thin, semi-transparent sample, they use 'epi-illumination', which delivers light through the objective lens itself to evenly illuminate the object surface. Reflected light then returns back through the same lens and on to the image sensor. Building upon this concept, we recently designed a compact epi-illumination microscope array (the "epi-MCAM"): 24 fully synchronized microscopes that epi-illuminate and stream video from reflective samples all at once. We've used it to rapidly image large reflective objects like full 30 cm semiconductor wafers and large printed circuit boards — objects that are slow and difficult to capture with a single microscope. We hope to scale up to even bigger arrays soon to create a new genre of high-throughput optical inspection! Please see our new paper below for more details about the epi-MCAM: https://lnkd.in/eBpTEFMU

Finally got around to reading the "Ballistic Microscopy" paper, and it is really incredible. The paper opens with a compelling idea; one I hadn’t explicitly thought about before: “Light and electron microscopy utilizes interactions of either photons or electrons with matter to create images...” In other words, we see small objects by literally hurling things at them. Particles bounce off the object and reflect back into a lens, or scatter into a detector, which we then use to "see." The question asked in this paper, then, is thus: Can we hurl even larger things at cells to image them? The answer is yes. The gist of ballistic microscopy is that you first "bombard living cells with millions of nanoparticles traveling at ~1000 m/s." Each particle rips through the cell, picks up a tiny amount of cytoplasm, and comes out the other side. If you place a hydrogel film underneath the sample, the nanoparticles will crash into it and get stuck there; just like shooting a bullet into a ballistics dummy. Finally, you take out these nanoparticles and study the molecules they carry, like by using mass spectrometry or really anything else. This method preserves spatial information. The "nano-bullets" rip through the cell in a straight line, meaning that the pattern in the hydrogel corresponds with the nano-bullet's path through the cell. Nano-bullets embedded in the left side of the hydrogel will be carrying proteins, metabolites, and other "pieces" from the same side of the cell. So TL;DR, you're getting SPATIAL and MOLECULAR information, without having to label cells with anything. "This is akin to a 'physical image' being captures on a hydrogel 'film'," the authors write, "with physical material captured on these nano-bullets." Each bullet is between 50 to 1,000 nanometers in diameter. This is small but not exceptionally small. A typical E. coli bacterium measures about 2 micrometers long and 1 micrometer wide. Human cells are quite a bit larger. The next step will be to increase the resolution of this method, perhaps by using smaller nanoparticles. But then there is a tradeoff; if the nanoparticles are TOO small, they need to be accelerated at much higher speeds or they won't penetrate cleanly, or their path of travel will get deflected and mess up the spatial information. This first paper is just a proof-of-concept, of course. It reminds me a bit of Expansion Microscopy, at least in the narrow sense that it's a super creative, original solution to solving a problem. In expansion microscopy, you use a swellable polymer gel to physically ENLARGE a biospecimen, rather than try to make a microscope that can see smaller objects. It's an inverse solution to the microscopy resolution problem. In the original expansion microscopy paper (from 2015), samples were only expanded ~4.5x in each dimension. More recent papers have upped this to ~20x in each dimension; a huge improvement. I expect similar improvements for ballistic microscopy.

# Yogeshwar Nath Mishra's Role in Advanced Microscope Development Dr. Yogeshwar Nath Mishra, an Assistant Professor at the Indian Institute of Technology (IIT) Jodhpur, has played a pivotal role in the development of a groundbreaking microscope technology. This innovation stands out due to its unique integration of three advanced components: 1. Ultrafast Laser: Enables the generation of extremely short pulses of light, allowing the microscope to capture phenomena occurring at incredibly fast timescales (femtoseconds to picoseconds). 2. Streak Camera: A highly sensitive device capable of recording the temporal evolution of light signals with ultra-high time resolution. It essentially "stretches" time, making it possible to visualize ultrafast events that are otherwise invisible to conventional cameras. 3. Advanced Computational Algorithms: These algorithms process the vast and complex data collected by the laser and streak camera, reconstructing high-resolution images and enabling detailed analysis of ultrafast processes. # Significance of the Technological Leap: - Unprecedented Temporal Resolution: The combination allows scientists to observe and analyze processes at the atomic and molecular level in real time, such as chemical reactions, biological events, and material transformations. - Broad Applications: This technology has potential uses in physics, chemistry, biology, and materials science, opening new avenues for research and innovation. - Indian Contribution to Global Science: Dr. Mishra’s work highlights the growing role of Indian institutions and researchers in pushing the frontiers of scientific instrumentation and research. The combination of an ultrafast laser, a streak camera, and advanced computational algorithms significantly improves microscopy by enabling: - Extremely Fast Imaging: The ultrafast laser generates very short light pulses, allowing the capture of rapid molecular or atomic events that traditional microscopes miss - High Temporal Resolution: The streak camera records these events with sub-picosecond precision, translating ultrafast changes in light into spatial information for detailed analysis - Advanced Image Reconstruction: Computational algorithms process the massive data from the laser and camera, reconstructing sharp, high-resolution images and extracting meaningful information from complex signals - Wide-Field, Non-Invasive Imaging: This setup allows real-time, wide-area imaging (up to square centimeters) of molecular processes in their natural state—without special sample preparation—at speeds up to 125 billion frames per second - Improved Dynamic Range and Noise Reduction: Algorithms and optical techniques enhance the streak camera’s dynamic range and temporal resolution while reducing background noise, resulting in clearer, more accurate measurements.