Development of Novel Non-Invasive Extractive Probes for Diagnosis of Malignant Hyperthermia

Date

2025-2-28

Author

Kır, Ayşegül Şeyma

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Malignant hyperthermia (MH) is a genetic disorder that leads to uncontrolled calcium release from muscle cells and can be fatal if left untreated. A contracture test using a freshly cut muscle is performed for diagnosis, but the invasiveness of the test necessitates a novel test to diagnose MH in a minimally invasive way. This study aims to develop a sensitive analytical tool that can be used to identify MH susceptibility without biopsy. For this purpose, a low-invasive technique, solid phase microextraction was chosen. To determine the extractive phase that should be used, hydrophilic-lipophilic balanced (HLB) polymer, HLB with strong cation and anion exchangers, polydivinyl benzene, and polymethacrylic acid were synthesized, characterized and immobilized on micro-sized nitinol wires using dip-coating. To determine the best extractive phase, their extraction performances were investigated in two different scenarios using targeted analysis approach for model compounds in PBS and untargeted metabolomic approach in plasma. Both results showed that HLB is the most successful extractive phase. In addition, targeted studies showed that methanol containing 0.1% formic acid or 0.1% ammonia are the best eluants for nonpolar and polar analytes, respectively. Since the goal of this study is developing a sampler for sensitive in-vivo extraction, HLB was also coated on fiber using electrospinning to investigate if this might result in enhanced extraction kinetics. Extractions performed in agarose gel (mimicking tissue) with both types of fibers did not show an overall advantage for electrospun-coated fibers which could be associated with structural blockage of fibrous structure by used glue.

Subject Keywords

Solid-phase microextraction, Electrospinning, Targeted metabolomics, Untargeted metabolomics, Malignant hyperthermia

URI

https://hdl.handle.net/11511/114099

Collections

Graduate School of Natural and Applied Sciences, Thesis