Abstract

Detection, preservation, and quantification of biomolecules in biological fluids and tissues are fundamental to biomedical research, clinical diagnostics and long-term health monitoring. However, most clinically relevant analytes such as protein biomarkers, antigens and antibody are structurally fragile and exist over wide dynamic ranges in complex matrices such as plasma, serum, and interstitial fluid. Their accurate measurement is often compromised by pre-analytical instability, proteolytic degradation, and the practical constraints of cold-chain storage and centralized laboratory infrastructure. These challenges are more pronounced in minimally invasive sampling routes such as interstitial fluid, where biomarker concentrations are lower and accessible sample volumes are limited. Simple and effective material-based strategies that simultaneously stabilize biomolecules, enrich analytes, and enhance detection sensitivity are therefore essential for advancing early diagnosis, therapeutic monitoring, and disease surveillance, particularly in at home care, rural clinics, and resource limited settings. In this thesis, we introduce a metal organic framework (MOF)-biohybrid platforms that address these challenges through molecular preservation, molecular trapping, and minimally invasive sampling. The first part focuses on zeolitic imidazolate frameworks such as ZIF-8 and ZIF-90 and shows that these materials can encapsulate fragile proteins and entire patient biofluids. Protein biomarkers in plasma, including prostate-specific antigen and panels of cancer-related proteins, as well as SARS-CoV-2 antigens and antibodies used in serologic assays, retain their structural integrity and immunoreactivity after storage at elevated temperatures when protected by these frameworks. Mechanistic design principles are established by quantifying how protein loading density influences ZIF-90 crystal morphology, crystallinity, thermal stability, and preservation efficacy. In the second part, we extend MOF functionality to three dimensional plasmonic biohybrid aerogels, where in situ MOF growth on bacterial nanocellulose and collagen scaffolds, combined with plasmonic nanostructures, yields multifunctional porous materials that analyte pre-concentration with surface enhanced Raman scattering and photothermal antibacterial activity. The final part focuses on microneedle-based devices for in vivo and human interstitial fluid monitoring. Here, conformal MOF coatings on antibody-functionalized microneedles stabilize capture reagents under prolonged thermal stress and ambient transport, while fluorescence amplification restores sensitivity in the face of low analyte concentrations and limited sample volumes. Validated in animal models and human volunteers, these MOF@MN platforms enable quantitative, minimally invasive detection of clinically important protein biomarkers and demonstrate a path toward cold-chain-independent, patient-centric monitoring. Take together, these studies proposed general design principles for MOF-biohybrid systems by relating biomolecule loading, crystal morphology, pore architecture and interfacial engineering to preservation efficacy and sensing performance. By connecting fundamental MOF chemistry with the design of diagnostic assays, three-dimensional sensing materials, environmental monitoring platforms and microneedle devices, it shows how MOF-based biohybrid systems can be engineered to enable environmental monitoring, decentralized diagnostics and continuous health monitoring without strict dependence on the cold-chain.

Committee Chair

Srikanth Singamaneni

Committee Members

Guy Genin; Jai Rudra; Jianjun Guan; Ying Chen

Degree

Doctor of Philosophy (PhD)

Author's Department

Interdisciplinary Programs

Author's School

McKelvey School of Engineering

Document Type

Dissertation

Date of Award

12-19-2025

Language

English (en)

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Available for download on Saturday, December 18, 2027

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