Events Calendar

ECE Seminar: Qing Xia

Title: Mid-infrared Photothermal Microscopy: Unveiling Hidden Signatures with Single-Biomolecule Sensitivity

Abstract: Biomolecular imaging is central to precision diagnosis and treatment. Mid-infrared photothermal (MIP) microscopy, a recently developed super-resolution infrared technology, provides dye-free access to chemical fingerprints, bridging important gaps left by fluorescence microscopy. Yet, challenges in sensitivity, speed, and molecular selectivity limit its ability to probe single bio-nanoparticles and individual biomolecules.

In this talk, I will present our recent developments of MIP microscopy that address these challenges. I will begin with a click-free imaging strategy that employs azido photothermal probes (APPs) as a molecular “GPS” to track carbohydrates in living cells, enabling visualization of their trafficking and interactions with high specificity while minimizing perturbation. Then, I will present two innovations that extend label-free MIP from the cellular scale to single nanoparticles and biomolecules. First, WIDE-MIP, a wide-field interferometric photothermal approach, leverages defocus-enhanced photothermal contrasts to significantly improve sensitivity and throughput. This platform enables high-throughput fingerprinting of single viruses, distinguishing DNA and RNA viruses, and identifying β-sheet enrichment in viral proteins. Second, our latest work IR-AMES integrates orthogonal evanescent scattering with infrared absorbance modulation to achieve 187 nm spatial resolution and single-biomolecule sensitivity. Beyond detecting nanoparticles such as viral vectors, lipid nanoparticles, and extracellular vesicles, this development has been recognized by the BU Ignition Award for its translational potential in gene therapy and precision medicine. Moreover, IR-AMES enables secondary-structure analysis of individual proteins, and in Alzheimer’s disease patient samples it revealed distinct structural signatures of Tau oligomers and fibrils that may be associated with toxicity. Together, these advances establish MIP microscopy as a versatile framework for imaging chemicals and chemistry from cellular to molecular scales, opening new opportunities for both fundamental discovery and translation into medicine.

Bio: Qing Xia received her Ph.D. in Analytical Chemistry from Nanjing University in 2021 and is currently a postdoctoral associate in Professor Ji-Xin Cheng’s group at Boston University. Her research focuses on innovations and applications of mid-infrared photothermal microscopy for nanoscale chemical imaging and biomedical analysis, and her work has been published in Nature Communications and Science Advances.