Research On Cell Microcapsules Preparation Via Digital Ejection Of Micro-fluids

Cell microcapsule is wildly applied in disease treatment, tissue culture, analysis of cell metabolism and3-D drug screening. Preparation of cell microcapsule rhythmically has important significance on integrated and automated manipulating of cell microcapsule subsequently. Droplet formation based on the microfluidic chip is expensive, has bad generality and negative influence on the cell activity.The key technology in cell microcapsule preparation is to divide the high viscosity cell suspending liquid to unified micro droplets. In this paper, based on the digital of micro-fluids, the pulse inertia driving principle, theory and the flow field characters of cell suspending liquid were analyzed, theoretical model of pulse moving cell suspending liquid in micropipette driven by pulse inertia force was built, the system parameters that had influence on the pulse flow of micro-fluids were determined qualitatively.Based on the digital of micro-fluids, an experiment system for micro-fluids ejection with pulse inertia force produced by the electromagnet impact on beam was built. Steady ejection of liquid and solid-liquid two-phase flow with high viscosity and low Re in micro-pipette was realized. The sodium alginate microcapsule and microcapsule with solid particles were respectively prepared rhythmically. The system has simple structure and fine micro-structural properties, and is versatile to the polarity of the liquid.Steady pulse ejection of cell suspending solution and rhythmically cell encapsulating were researched. Based on the digital of micro-fluids pulse ejection,10～103μm scale cells were encapsulated rhythmically and the system was well adapted to different size cells and heterogeneous cells. The average diameter of cell microcapsules prepared could reach as small as30μm, and was smaller than those prepared by other method such as pressure spray, electrostatic spray. The standard deviation could be less than30μm, and the microcapsules prepared were well mono-disperse. The size and size distribution of cell microcapsule could be changed by adjusting driving voltage and inner diameter of the micro-nozzle. This method was superior to microfluidic chip on the cell activity influence and cell microcapsule size control.Single cell microencapsulating based on the digital of micro-fluids was researched. Cells could be single lined when the nozzle diameter was less than two times of the cell size. The cells number in a capsule could be changed by adjusting the pulse ejection step length. When the step length was less than two times of the cell diameter, a single cell could be dispensed and encapsulated rhythmically. The size and size distribution of cell microcapsule could be changed by adjusting the driving voltage and ratio of the cell size and nozzle diameter.A kind of coaxial micro-nozzle for pulse ejection was designed and fabricated. The steady pulse ejection state and micro ejection character of low Re coaxial fluid were experimentally studied, and pulse ejection of coaxial fluid and cell microencapsulating rhythmically were researched. The diameter ratio and relative geometric position of the coaxial micro-nozzle in steady ejection state were determined, and the coaxial and synchronous pulse ejection of cell suspending solution and sodium alginate solution was realized. Cell co-microcapsules were prepared through’rhythmically method’. Direct testing of cell activity was realized by co encapsulation of lymphocyte cells and Trepan blue solution.