An integrated MEMS syringe for advanced drug delivery: Design, fabrication and fluid mechanics of suspension flow through microneedle arrays.

摘要

New approaches for drug delivery seek to enable improved patient comfort as well as to provide an improved level of care. New approaches are especially important for drugs that cannot be administered orally. Liquid and lyophilized drugs can be delivered under the stratum corneum because of rapid diffusion of the drug into the capillary bed under the skin.; For this purpose, a syringe has been developed and fabricated using microfabrication to make an array of hollow, out-of-plane silicon needles using a combination of DRIE and isotropic etching. The needles have a typical height of 200μm and a lumen of 40μm. Their shape has been designed for robustness against bending moments and shear forces.; The fluid mechanics of drug delivery through the micro-needles has been studied for a homogeneous, Newtonian fluid. To understand delivery of a lyophilized drug, flow of suspensions through the needles has also been studied. During these experiments, clogs form unexpectedly under a large range of conditions.; Visualization shows that clog formation starts inside the entrance of the flow channel, which is a region where the particle interaction frequency is high. Dimensional analysis of experimental data reveals that the total amount of solids passing through a channel before complete clog formation depends only on the sizes of channel and particles. Quantitative investigation of the flow field has been performed using Digital Particle Image Velocimetry (DPIV) in combination with numerical simulations. A model is developed for shear-induced particle agglomeration, which conforms to observations as well as theory to describe clog formation. The maximum shear rate at a channel inlet can be reduced with a two-step inlet funnel.; Deformable PDMS reservoirs for the drug suspension are cast from a silicon mold and are then bonded to the silicon device wafer, which allows for batch fabrication of prefilled MEMS syringes. The prototype of a MEMS syringe has been tested with a model suspension of 0.7μm large fluorescent beads in water. Most of the injection occurred deeper than 20μm into the sample tissue, which is the desired location for epidermal delivery. A method for packaging of the syringe has been proposed.