POINT-OF-CARE CLINICAL DIAGNOSIS USING MASS SPECTROMETRY SYSTEM

2019-01-16T20:47:32Z (GMT) by Ran Zou

Point of care (POC) diagnosis is essential in personalized treatment to obtain effective clinical outcomes when the patient is on site. And Mass spectrometry (MS) system promotes the applications of rapid sampling ionization, which could be a tool for fast disease determination. In this thesis, a miniature MS system was firstly developed for POC tissue analysis. Lipid profile in rat organs were demonstrated. By coupling with online Paternò–Büchi (PB) reaction, fast determination of lipid C=C bond location isomers was realized. The system was applied to quantitatively analyze the change of lipid C=C location isomers between mouse normal and cancerous samples. The intensity ratio of fatty acid 18:1 (D9) and 18:1 (D11) in wild type breast tissue was calculated to be 2.881, while the ratio in tumor breast tissue was 0.667. The direct sampling-based miniature MS system is potential for POC analysis of lipid profiles and lipid biomarkers discovery.

Secondly, an integration of paper-capillary spray and MS make it possible to analyze dried blood samples instantly in clinical laboratory and hospital. Quantitation of ratio between deuterate Phenylalanine and deuterate Tyrosine was achieved by using paper spray and paper-capillary spray MS directly, without any pretreatment of blood samples. Furthermore, these methods could generate calibration curves which enable the calculation of Phenylalanine concentration in whole human blood within 60 seconds. This disposable design is a promising application for point-of-care (POC) PKU analysis in newborn screening.

At last, an increased in free fatty acids (FFAs) of cereals was observed during storage, and a simple and direct rice quality assessment was performed using nanoESI (Nano-Electrospray Ionization) mass spectrometry method. Six fatty acids including palmitic, oleic, and linoleic acids were compared between different rice species, growth regions and harvest years. 2D and 3D linear discriminant analysis (LDA) methods were deployed and a good sample separation was achieved. This direct sampling method of extracting FAs from rice surface combined with MS is suitable for industrial use in rapid identification for large number of samples.