Development and Characterization of a Custom Syringe Pump for Delivery of Picoliter Range Liquid Volumes

This work is part of a larger investigation into a chemical-based implant capable of delivering controlled, discrete amounts of liquid therapeutic agents. One aim of the investigation includes an examination into the efficacy and feasibility of eliciting physiological responses of retinal neurons when chemicals are focally presented by means of engineered delivery devices. To approach this aim, the engineered delivery device must meet several broad specifications such as fast (<1 second) discrete dispensing over a wide range of volumes (picoliters to nanoliters) with high accuracy and repeatability. Additionally, the dispenser must be leak-proof and robust enough to withstand the high pressures and forces involved in dispensing through small flow lines (<100µm in cross-sectional diameter). Currently, a commercially available delivery device does not adequately meet the delivery requirements of this project. Therefore, motivated by a need for such a system, the goals of this thesis are to build a bench-top dispenser and develop methods of testing and characterization of its delivery. A custom-built, high precision syringe pump is designed and assembled to meet the design criteria with exceptionally accurate and repeatable volume dispensing. Further, design goals for dispensed volume and flow rate are confirmed by testing and characterization of the dispenser under a variety of loading conditions. Hydraulic circuit theory is applied to develop a model to calibrate and predict flow rates for interchangeable end capillaries in the microfluidic system. Finally, the dispenser is used to eject liquid volumes of dye from the dispensing capillary end while inserted into agarose gel to simulate dispensing into neuronal tissue. Ejection profiles are imaged and used to measure convection and diffusion within the gel via application of the Beer-Lambert Law. A finite element model is also developed to correlate experimental phenomena with basic theory. Concentration profiles are then assessed to determine which flow rates are most effective in elevating chemical concentration at a prescribed distance into the gel. The experimental observations are compared with theory and results are used to suggest flow rates for dispensing into tissues while avoiding flow induced displacement of the tissue.