- Starts: 10:00 am on Tuesday, February 11, 2025
- Ends: 12:00 pm on Tuesday, February 11, 2025
Title: Advancing Mid-Infrared Photothermal Spectroscopic Imaging from Bench to Bedside
Presenter: Mingsheng Li
Advisor: Professor Ji-Xin Cheng
Chair: TBA
Committee: Professor Jerome Mertz, Professor Irving Bigio, Professor Darren Roblyer, Professor Ji-Xin Cheng.
Google Scholar Profile: https://scholar.google.com/citations?user=HlGqX34AAAAJ&hl=en
Abstract: Providing molecular fingerprint information, infrared (IR) spectroscopy has found extremely broad biomedical applications. However, In vivo IR spectroscopy faces challenges due to poor sensitivity in reflection mode and low resolution at micrometer scale. To break this barrier, we report an oblique photothermal microscope (OPTM) to enable ultrasensitive IR spectroscopic imaging of live subjects at sub-micron resolution. Classic photothermal measurement captures only a small fraction of probe photons through a pinhole to extract the photothermal signal. Instead, OPTM uses a differential split detector placed on the sample surface to collect 500-fold more photons and suppress the laser noise by 12 fold via balanced detection. Leveraging its improved sensitivity, OPTM enables low-dose IR imaging of skin without photodamage. Depth-resolved in vivo OPTM imaging of metabolic markers beneath mouse and human skin is shown. Furthermore, we demonstrate in vivo OPTM tracking of topical drug contents within mouse and human skin. OPTM presents a highly sensitive imaging platform for in vivo and in situ molecular analysis.
OPTM utilizes photothermal-modulated phase gradients as a readout for IR absorption, providing high sensitivity to local microstructural environments. However, when measuring the bulk thermal lensing effect of diffuse molecules in skin, such as glucose, photon propagation becomes scrambled, resulting in a speckle pattern in the far-field plane. Due to destructive interference within the speckle pattern, traditional single-element photon detectors are ineffective for measuring average intensity changes. To overcome this challenge, we propose speckle-detected photothermal (SDP) spectroscopy, which leverages a virtual lock-in camera to capture the far-field speckle pattern. By computationally analyzing the speckle correlation coefficient, SDP significantly enhances sensitivity in detecting bulk thermal lensing effects. This approach enables highly sensitive measurements of glucose molecular signatures in the interstitial fluid of human skin, presenting a promising tool for long-term, noninvasive blood glucose monitoring. SDP has the potential to facilitate diabetes diagnosis and clinical management, offering a breakthrough in metabolic health monitoring.
Collectively, innovations like the OPTM and SDP approaches promise transformative applications in molecular diagnostics and precision medicine, offering powerful platforms to track biochemical changes and therapeutic interventions from bench to bedside.
- Location:
- PHO 428