Cavity-Enhanced Laser-Induced Fluorescence for Real-time Breath Acetone Monitoring

Abstract

Diabetic ketoacidosis (DKA) is a life threatening complication in children with type 1 diabetes. In DKA, the body breaks down fatty acids as an alternative energy source producing high concentrations of acidic blood ketones. Normally, DKA is treated by a ``guess'' dosage of intravenous insulin infusion following blood analysis. There is an unmet need for alternative, non-invasive methods to the inaccurate, untimely blood tests to monitor each patient's response to the treatment in real time. This will help in determining the optimum insulin dosage and adjusting the treatment protocol. Breath-acetone measurement is a promising non-invasive alternative as it is proportional to blood ketone concentrations.

This thesis describes building a device based on the cavity-enhanced laser-induced fluorescence (CELIF) technique for real-time, online, non-invasive breath acetone measurements. CELIF combines the sensitivity of laser-induced fluorescence (LIF) and the absolute measurement capabilities of cavity ring-down spectroscopy (CRDS) into one cross-correlated technique.


The device is capable of making an acetone CELIF measurement in 100 ms, with a concentration dynamic range of 1.6--2000 ppm, covering the range of breath acetone concentration a DKA patient might have. The response time of the device is fast enough to follow a real breath pattern, with a rise time of the CELIF signal of 370 15~ms, and a 90--10 fall time of 850 21~ms, which is enough for the signal to rise and find the maximum acetone concentration, then decay back to the background level before the next breath arrives. The performance of the acetone CELIF device was validated by using a selected-ion flow-tube mass spectrometer (SIFT-MS). The results show that this device is useful for reliable online breath acetone analysis. Subsequently, the validated CELIF device was tested for breath acetone measurements in fasted healthy human subjects, using a home-built, online, buffered end-tidal breath sampler.