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ECE PhD Thesis Defense: Danchen Jia

Title: Mid-Infrared Photothermal Imaging: from Cellular Volumes to Nanostructured Interfaces

Presenter: Danchen Jia

Advisor: Professor Ji-Xin Cheng

Chair: TBA

Committee: Professor Ji-Xin Cheng, Professor Siddharth Ramachandran, Professor Jerome Mertz, Professor Lei Tian

Google Scholar Link: https://scholar.google.com/citations?user=LnNn-oYAAAAJ&hl=en

Abstract: Mid-infrared photothermal (MIP) microscopy enables subcellular chemical imaging of key metabolites in life science. However, three-dimensional (3D) chemical imaging speed is not sufficient for live cell studies. This dissertation developed two methods for volumetric chemical imaging at video rates. Firstly, by exploiting thermo-sensitive fluorescence, we demonstrate fluorescence-detected mid-infrared photothermal Fourier light field (FMIP-FLF) microscopy, achieving double-shot 3D chemical imaging. FMIP-FLF visualized protein in bacteria and revealed altered lipid metabolism in drug-resistant pancreatic cancer cells. Secondly, we present photothermal relaxation intensity diffraction tomography (PRIDT) that encodes IR-induced refractive index changes through photothermal relaxation and reconstructs them via intensity diffraction tomography. PRIDT achieves 15 Hz volumetric chemical imaging, enabling label-free, video-rate visualization of lipid and protein metabolism in live cells.

Beyond imaging speed, MIP sensitivity is limited by the weak interaction between IR photons and molecules. To address this, two ultrasensitive infrared photothermal spectroscopy methods were developed. We first report mid-infrared encoded plasmonic scattering (MIREPS) spectroscopy, which leverages a nanoparticle-on-film cavity as a spectroscopic sensor for the analyte molecules inside the nanogap to detect nitrile or nitro groups in ~130 molecules. Next, we introduce metasurface-enhanced infrared photothermal (MEIP) microscope, which achieved a detection limit as low as 0.24 monolayer surface coverage of bovine serum albumin with mid-infrared-resonant metasurface.

Together, these strategies for high-speed, high-throughput, high-sensitivity and 3D-resolved infrared photothermal imaging open pathways for quantitative chemical analysis of low-abundance molecules in living systems.