Parahydrogen-induced polarization in microfluidic devices

Abstract

Microfluidic lab-on-a-chip (LoC) systems hold greatpotential for the study of live microscopic cultures of cells, tissue samples,and small organisms. This is because the LoC microenvironment can be engineeredto precisely simulate the physiological or pathological state of an organism ina highly controlled, repeatable manner. High-resolution Nuclear MagneticResonance (NMR) spectroscopy is an ideal tool to follow chemical andbiochemical processes in LoC due to its non-invasive nature, chemicalspecificity and the ability to quantify metabolites, yet it is rarely used incombination with LoC due to its low sensitivity. Integration of hyperpolarizationmethods such as parahydrogen induced polarization (PHIP) enables NMR signals tobe enhanced by several orders of magnitude. This would enable quantitativestudies of a wider range of metabolites in such volume limited systems by NMR.This thesis presents the advances made to improve the efficiency of PHIP in LoCand to generalise the approach to ¹³C - hyperpolarization, a nucleus of choicefor biological applications. This is achieved by developing aspatially-resolved kinetic finite element model of a PHIP reaction in LoC. Themodel is then used to design an optimised micro-reactor that integrates theformation, sample transport, RF excitation and observation of¹³C-hyperpolarized metabolites onto one compact device at the microscale.

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