Spatially resolved, quantitative measurement tools for complex, three-dimensional nanoporous systems

Spatial measurements can provide invaluable insight into complex, multidimensional systems by highlighting heterogeneities and/or features otherwise masked by bulk measurements. However, workflows designed to quantify spatial information require a multidisciplinary approach that includes meticulous consideration of the optics governing the system and spatial readout method to generate data that accurately represent the system of interest. Consequently, there is a need for robust workflows that quantify not only spatially resolved measurements, but also the accuracy of those measurements. To address this need, we sought to design spatially resolved quantification workflows to characterize salient properties of two distinct nanoporous systems: (1) equilibrium distribution of solutes between hydrogel and free solution, which can guide hydrogel design for specific functionalities, and (2) ultraviolet-C (UV-C) dose distribution across N95 filtering facepiece respirators, a metric that underpins the implementation of safe and effective decontamination protocols during crisis-capacity N95 shortages such as that observed during the COVID-19 pandemic./nWe will first explore how three-dimensional quantification of equilibrium solute distributions between a nanoporous hydrogel and free solution (thermodynamic partitioning) can highlight important functional hydrogel properties. We will discuss the advantages and disadvantages of optical sectioning microscopy techniques to quantify thermodynamic partitioning, emphasizing the impact of measurement artefacts caused by refractive index mismatches in the optical path. To address these measurement artefacts, we will introduce and validate “aberration-compensated laser scanning confocal microscopy” (AC-LSCM), a dual technique and analytical pipeline that robustly quantifies spatially resolved thermodynamic partitioning in situ. Using AC-LSCM, we will examine how various structural changes introduced to the hydrogel influence not only the spatial partitioning behavior of solutes as compared to unmodified hydrogels, but also hydrogel-induced artefacts that can confound quantification./nNext, we will transition from studying three-dimensional nanoporous materials filled with water (hydrogels) to those filled with air (N95 filtering facepiece respirators). We will explore the importance of spatial resolution for UV-C dose measurements, especially on complex three-dimensional targets such as multilayered N95 respirators. To elucidate the underlying causes and effects of common UV-C dose measurement errors, we will review important optics principles governing UV-C spatial distribution and detection that reveal existing incompatibilities between the design of UV-C decontamination systems and UV-C sensors. To inform and validate safe and effective UV-C decontamination protocols of N95s, we apply principles from optics, physics, and colorimetry to convert UV-C photochromic indicators (PCIs) into robust quantitative UV-C dosimeters for on-N95 dose characterization. Using PCIs, we will characterize the impact of N95 shape on UV-C dose distribution and discuss important considerations associated with UV-C dose quantification using PCIs related to accuracy, UV-C specificity, dynamic range, and color readout./nWe will then discuss how we can apply PCI quantification to perform simultaneous spatially resolved measurements of UV-C dose and viral inactivation across N95 respirator surfaces. By harnessing high resolution and modular optical simulations, we will examine how in situ PCI measurements synergize with in silico optical simulation results to rapidly inform design of dual UV-C dose/viral inactivation experiments. The results of these experiments highlight how N95 respirator shape substantially narrows the range between effective and N95-damaging UV-C treatments./nFinally, we explore the use of planar optical attenuators to extend PCI dynamic range and investigate how additional material in the optical path impacts measurement accuracy. Through an analytical model, we discuss the difference between diffuse and specular materials and material properties that influence both attenuation and measurement accuracy. For two example materials, we observe an inherent tradeoff between extending the dynamic range and maintaining measurement accuracy through angle-independent transmission./nIn total, we introduce quantitative workflows to scrutinize, with spatial resolution, two complex, three-dimensional nanoporous systems: hydrogels (where nanopores are filled with water), and N95 filtering facepiece respirators (where nanopores are filled with air). Using a multidisciplinary framework, we discuss the origin of common measurement artefacts that can be captured during data acquisition and how we sought to address such artefacts. While careful consideration of the limitations of any measurement tool are paramount, we anticipate these measurement tools will continue to support and advance understanding of three-dimensional nanoporous systems by incorporating spatial information as part of the measurement readout.

Advisor: Herr, Amy E.