Chemical Imaging, Spectroscopy, and Theory
We develop next generation Chemical Imaging instrumentation for conducting biomedical investigations at micro- and nano- length scales. Furthermore, we enhance the analytical capabilities of our instrument with phase and dichroism capabilities. With the in-house design of optics, electronics, mechanics, and software, our custom-built microscopes are instrumental in bridging the gap between theoretical predictions, experimentation, and real-world technological translation.
Infrared Laser Microscopy
We develop advanced infrared microscopes powered by quantum cascade lasers (QCLs) to capture detailed images quickly, with low noise and high spatial resolution. Our custom-designed optical system enables precise scanning of laser light over large areas using specially engineered lenses. This allows us to create clear, speckle-free images of entire tissue slides without the need for dyes or extensive processing, making label-free imaging of biological samples faster and more practical.
Recommended publications:
Nano-scale Infrared Imaging
We combine atomic force microscopy (AFM) with infrared spectroscopy to create detailed chemical maps at the nanoscale, overcoming the traditional resolution limits of infrared light. This unique approach allows us to visualize structures within cells while simultaneously revealing their chemical composition.
Recommended publications:
Vibrational Circular Dichroism Spectroscopy
Vibrational circular dichroism (VCD) is a powerful technique that provides detailed information about molecular structure and shape. Many pharmaceutical and biological molecules exist as pairs of mirror-image forms, called enantiomers, which can behave very differently in the body. Our lab designs and builds highly sensitive VCD spectrometers using quantum cascade lasers to map molecular chirality and better understand these important differences.
Recommended publications:
Image Formation Theory
We study how images are formed by simulating the behavior of electromagnetic fields, considering diffraction, scattering, and interference effects to improve imaging techniques.
Recommended publication:
- Large Fluorescence Enhancement via Lossless All-Dielectric Spherical Mesocavities – ACS Nano 2023 [link]
Quantitative Phase Imaging
We develop label-free quantitative phase imaging techniques to capture high-resolution details of cell and tissue structures. We pioneer single-shot quantitative phase gradient imaging (ss-QPGM) to simultaneously capture multiple polarization components and reconstruct detailed phase images in real time.
AI-Enhanced Chemical Imaging for Clinical Translation
Our lab is pioneering AI-enhanced chemical imaging techniques to accelerate clinical translation. We develop deep-learning algorithms that streamline the analysis of chemical images acquired by our custom instruments, with two primary objectives: first, to transform stain-free chemical imaging data into a format interpretable by pathologists—a process we call “virtual staining,” based on image-to-image translation into realistic histological stains; and second, to build autonomous pathology models that directly predict specific disease states from raw chemical images. Throughout our work, we integrate tools to quantify model uncertainty and detect potential hallucinations, coupling these with mitigation strategies to ensure our algorithms are both robust and safe for deployment in clinical settings.
Recommended publications:
- Stain-less staining for computed histopathology – Technology, 2015, DOI: [link]
- Deepfake Histologic Images for Enhancing Digital Pathology – Laboratory Investigation, 2023, DOI: [link]
- INSTRAS: INfrared Spectroscopic imaging-based TRAnsformers for medical image Segmentation – Machine Learning with Applications, 2024, DOI: [link]
Systems Pathology: Bioengineered Tumor and Disease Models
Bioengineered Tumor and Disease Models serve as powerful tools to investigate complex biological processes by recreating human tissues in controlled environments. One of our flagship efforts is MASCOT (Manufacturing Agile and SCalable Organoid Tumor models), which leverages digital manufacturing to produce uniform, high-throughput tumor constructs for studying cancer dynamics and therapeutic responses. Beyond MASCOT, we also bioprint diverse tissue models, enabling the exploration of development, regeneration, and disease in physiologically relevant 3D systems.
Biological & Micro-Fabrication
The micro-fabrication subgroup utilizes 3D printing to create complex and physiologically relevant models. Specifically, we create complex vascular networks inside cell-laden hydrogels to achieve larger and more complex tissues constructs. These intricate models may find application in accurate disease modeling and regenerative medicine.
Tailored Nanosensors
The development of nanoparticle probes and small molecules labels enables the rapid identification and quantification of molecular species using infrared spectroscopy. Specifically, we develop probes and methods to produce them in a tunable manner using microfluidic technology. These tailored molecular sensors may find use in the detection of biomarkers with clinical significance and address the lack of specific probes for infrared microscopy.