Quantum cascade laser-based mid-infrared spectroscopic imaging systems with polarization capabilities

Infrared (IR) imaging is an emerging field that seeks to image the molecular world by combining the spatial specificity of digital imaging with the chemical sensitivity of spectroscopic measurements. As opposed to extrinsic contrast-enhancement techniques, the origin of contrast in IR imaging is inherent to the specimen’s molecular composition and is dependent upon interaction of the specimen with light. Specifically, IR microscopy seeks to measure the molecular content of biological samples by probing fundamental vibrational modes optically, thereby providing a reagent-free, nondestructive tool with wide applications such as early disease detection and diagnosis. However, some crucial barriers to achieving this goal are the long acquisition times, limited spatial detail, and limited understanding of light-matter interactions. Moreover, efficient techniques to map the molecular organization, still remain sparse. Building upon the recent advances in quantum cascade lasers (QCLs), this thesis research is centered around developing advanced IR spectroscopic imaging platforms to address these three paramount challenges. The research work can be divided into two parts. The first part emphasizes the design and mathematical modeling of fast optical systems. Chapter 1 focuses on the limitations of existing hardware configurations and lays the groundwork for systematically addressing each of the aforementioned problems through optical design considerations. Next, in Chapter 2, using a decision theory framework, we demonstrate that a combination of spatial and spectral information improves the perceived spatial resolution limit. We also utilize a similar rationale of likelihood approach to show an improved performance in the detection limits of a representative IR instrument. The demonstrated ability to detect minute quantities of biomolecules, such as proteins, is of crucial interest to a wide variety of applications, including forensic studies, regulatory monitoring, and contaminant residue detection. As with standard microscopy techniques, the optical configuration plays a critical role in ascertaining the overall system performance. Towards the goal of reducing the biopsy to diagnosis latency, we develop the first instance of a laser scanning microscope enabling ten-fold improvement in speed. In Chapter 3, we present the design and complete performance characterization of a mid-infrared laser scanning microscope. The spectral performance is characterized using a variety of metrics, including the signal-to-noise ratio, spatial resolution, and chromatic focal shift. The developed technique facilitates label-free classification of surgical tissue sections within minutes as opposed to hours with state-of-the-art objective or stage scanning designs. Chapter 4 marks the transition to the second family of topics in this dissertation. The applicability of the developed rapid laser-based design spans beyond measuring molecular contrast to enable polarized measurements of the biomolecules and polymers. However, effects of focusing optics, detector configurations, and reflective elements are often overlooked and could have crucial effects on polarized measurements. Hence, in Chapter 4, the optical design considerations are revisited to reduce polarization aberration effects in a typical QC laser (QCL)-based spectroscopic system. The approach then demonstrates polarization IR imaging, in Chapter 5, and the first instance of imaging site-specific chirality of molecules in Chapter 6. The developed paradigm can elucidate the secondary structures in a sub-microliter sample volume of biomolecules such as proteins and amino acids. Together, these measurements are not only faster than the state-of-the-art measurements but also provide the ability to visualize microscale distribution of molecular chirality for the first time. Taken altogether, my research encompasses a combination of fundamental information theory approach and optical design that pushes the spatial and spectral limits of mid-IR imaging.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Electrical & Computer Engr

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2023

Author dc:creator

• Phal, Yamuna Dilip

Contributors dc:contributor

• Bhargava, Rohit
• Eden, J. Gary
• Gruev, Viktor
• Dragic, Peter
• Zhao, Yang

• Mid-infrared Imaging
• Spatial Resolution
• Resolution Limit
• Laser Scanning Microscopy
• Polarization
• Vibrational Circular Dichroism
• Chirality
• Quantum Cascade Lasers
• Spectroscopy
• Spectral Imaging

Statement dc:rights

• © 2023 Yamuna Phal

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/121239

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F121239