Advanced microfluidic impedance cytometry for point of care analysis

Abstract

Microfluidic impedance cytometry is the dielectric characterisation of single particles flowing through a microfluidic channel. Microfluidic impedance cytometry offers a novel solution to counting and discrimination of different particles and cells. One application is discrimination of different blood cell types in a low cost Point of Care device. However, the accuracy of currently available systems is poor and inadequate for clinical use. A full numerical model, developed in this research, demonstrated that the main source of measurement inaccuracy relates to the position of the particle in the micro-channel. Particles travelling at the top or bottom of the channel close to the electrodes were found to have a higher impedance signal compared with particles travelling through the centre of the channel. Counter-intuitively, the model also showed that although the electrode geometry is symmetrical, the variation in signal is asymmetric about the vertical position of the particle within the channel. A new electrode geometry was developed to minimise particle positional dependence. When combined with new signal processing techniques which were also developed, this led to marked improvements in measurement accuracy. For example, the coefficient of variation of monodisperse beads were half the manufacturer's data.

Applications of the improved device were investigated by analysing a range of different cell types in blood. Measurements of the distribution width of red blood cells were successful and found to be within the known clinical range. It was also shown that combined with pre-enrichment techniques, the device successfully detected clinically relevant concentrations of individual tumour cells in a background of 106 times more white blood cells. In order to use microfluidic impedance cytometry for diagnostic blood counting applications, lysing of the more numerous red blood cells is required. Lysing methods suitable for implementing in a Point of Care device were evaluated and a stirred mixing system was developed. In summary, this thesis describes a new, high accuracy microfluidic impedance cytometer which has the potential to be integrated into a miniature blood counting device for Point of Care analysis.

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ORCID for Hywel Morgan: orcid.org/0000-0003-4850-5676

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