AVS 59th Annual International Symposium and Exhibition | |
MEMS and NEMS | Monday Sessions |
Session MN-MoA |
Session: | Multi-scale Interactions of Materials and Fabrication at the Micro- and Nano-scale |
Presenter: | N.M. Elman, Massachusetts Institute of Technology |
Authors: | S. D'hers, Buenos Aires Institute of Technology, Argentina A. Alexander-katz, Massachusetts Institute of Technology N.M. Elman, Massachusetts Institute of Technology |
Correspondent: | Click to Email |
Rapid Reconstitution Packages (RRPs) represents a breakthrough microfluidic platform to use pharmaceutical drugs in ambulatory settings without the need for refrigeration. RRPs were designed as microfluidic cartridges, keeping drugs in lyophilized form (powder) for years and perform on demand reconstitution in the order of milliseconds. The unique integration of a dual multi-scale computational and experimental model with nano-materials and microfluidics provides the scientific basis towards the development of an ultra-portable platform for long term storage and extremely rapid reconstitution. The device architecture consisted of mixing microstructures, fabricated with Stereo Lithography Apparatus (SLA) with biocompatible materials. Rapid prototyping provided a quick turnaround experimental model for validating computational models, rendering a unique methodology for optimization. Experimental setup was intended to emulate temperature fluctuations in ambulatory environments. Experiments were performed using standard analytical methods on RRPs containing drugs exposed to temperatures in the range of 25-65 C. High Performance Liquid Chromatography (HPLC) assays for quantifying reconstitution, and Enzyme-Linked Immunosorbent Assays (ELISA) for activity were performed. Several drugs were tested, including atropine for resuscitation, and tissue plasminogen activator (tPA) for treatment of thrombosis. The design was optimized in parametric software and tested for manufacturability and functionality using Computed Fluid Dynamics (CFD) analyses. Design optimization using the CFD models was performed with the goal of reducing drug retention in the device and tailoring drug concentration profiles during activation. A consistent fluidic representation was adopted to model drug dissolution and diffusion. The numerical scheme was validated through computational and laboratory tests for drug dose and concentration profile. Experimental results reveal the importance of the combined use of computational and experimental techniques. The convergence of these unique techniques allows exploitation of physical processes at the nanometer and micrometer scales to investigate the lyophilization and reconstitution processes, overall rendering a synergistic computational and experimental methodology for development of therapeutic microdevices. The use of RRPs will result in significant improvement in logistics for a number of civilian and military applications.