Microfluidic Ultrafiltration and Acoustophoresis as a Human Breast Milk Optimizing Plateform for Neonatal Nutrition

In recent years, research has highlighted that breast milk with higher concentrations of lipid and protein could benefit to the survival rate and quality of life of preterm infants. However, to date, there is no clinical means available to separate, concentrate and recombine those components directly from the breast milk of the mother. In this thesis, a microfluidic approach was chosen to provide a reliable solution for the optimization of human breast milk. The strategy for the optimization consists of a first separation of the fat globules providing skim and fat-enriched volumes of milk. The skim milk is then processed by a second device that enriches the protein content and removes a part of lactose. Both enriched milks are then recombined together to provide optimized human breast milk. The first separation step was achieved with the development of an acoustophoresis microchip that resulted in an effective separation of the fat globules from raw whole human milk. In this context, a combined and theoretical model that simulates the concentration of milk lipids at the outputs of an acoustophoresis device was developed for a variety of experimental conditions. The model is based on the measurement of the acoustic energy density in the separation channel as well as the acoustic transverse force acting on the lipid particles. A first set of experimental separations of raw milk with processing flow rates varying from 0.04 to 1.2 mL/min showed a good accordance with the simulated results of the model. Specifically, the device can concentrate lipids to 113%, and simultaneously deplete them to 31% with an input flow rate of 0.1 mL/min. The enrichment of the protein content with the simultaneous removal of lactose was accom- plished with the development of a novel microfluidic device that incorporates a commercially- available ultrafiltration membrane. The high surface-to-volume ratio of an optimized meander microchannel that covers the membrane surface enabled a continuous process of skim milk. The device can provide a repeatable two-fold enrichment of the protein content with a limited increase of the lactose concentration (1.3 fold) with an input flow rate of 0.23 mL/min. This result was obtained in a single pass over a small membrane area of 9 cm2. Furthermore, three consecutive passes through the device increased the protein concentration to 5.2 times. Together, the acoustophoresis and the microfluidic ultrafiltration provide the essential building units of a breast milk optimizing platform that may revolutionize the nutritional care of preterm infants.