Engineered Microneedle Patches for Biomarker Quantification and Interstitial Fluid Collection

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Kim, Youngeun
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School of Chemical and Biomolecular Engineering
School established in 1901 as the School of Chemical Engineering; in 2003, renamed School of Chemical and Biomolecular Engineering
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https://hdl.handle.net/1853/76819
Abstract
Interstitial fluid (ISF) is a fluid that surrounds cells and tissues of the body. ISF can be collected in a minimally invasive manner using microneedle patches (MNPs) for diagnostic application. Different types of MNPs can be used to collect ISF or directly quantify biomarkers in ISF. Here, we developed two different types of MNPs – antibody-coated and hydrogel MNPs for quantifying biomarkers in ISF. First, we fabricated mechanically strong polystyrene MNPs and successfully coated the surface of the MNPs with antibodies via passive adsorption. Then, the MNPs were used to quantify two protein biomarkers of tuberculosis (TB) in vitro via enzyme-linked immunosorbent assay (ELISA) with optimized sensitivity. With our work, we demonstrated that MNP-based ELISA can potentially be used to diagnose different stages of TB. Second, we developed hydrogel MNPs that can be applied to the skin to collect ISF and then removed to quantify the biomarker of interest. With formulation optimization, we developed mechanically strong crosslinked carboxymethylcellulose (xCMC) hydrogel MNPs that could collect ~4 μl of ISF in 20 minutes in a safe and simple manner. To demonstrate the utility of the collected fluid, we collected ISF from ex vivo skin that was incubated with lidocaine, our topical drug of interest. We specifically characterized lidocaine partitioning behavior in skin, ISF, and xCMC-MNP to enable quantitative relationships between concentrations measured in xCMC-MNP and concentrations expected in skin and ISF. Then, we topically delivered lidocaine using a commercially available ointment product and measured lidocaine concentration in xCMC-MNP and skin using the developed approach. Overall, our work shows that antibody-coated solid MNPs and hydrogel MNPs can be used to quantify biomarkers in ISF, thereby further broadening the utility of ISF for immunodiagnostic application and topical drug bioavailability studies.
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2023-12-12
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Dissertation
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