Digital Manufacturing Techniques for Microfluidic Device Fabrication

Abstract

Microfluidic devices are currently used in a wide range of scientific and biomedical areas such as tissue engineering, cell biology, and implantable devices. Lab-on-a-chip research utilizing microfluidic devices has advanced significantly over the last decade and provides advantages of miniaturization, uniformity, accuracy, reproducibility, fluid/cell/tissue manipulations, rapid sample processing, and precise control of fluids. Traditional methods of manufacturing microfluidic devices are based on semiconductor microfabrication technology. Specifically, a combination of photolithography and soft lithography have been used where devices are built by molding a transparent, elastomeric, and biocompatible material called polydimethylsiloxane. However, this fabrication process is extremely labor intensive, time consuming, expensive, not amenable for high-throughput manufacturing, and makes commercialization of microfluidic devices difficult. Digital manufacturing techniques centered around computers that automate the fabrication process are alternatives with high potential for reducing fabrication costs and time. Techniques such as laser micromachining and 3D printing, specifically stereolithography (SL), are explored in this research. Laser micromachining was used to engrave microchannels onto plastic poly(methyl methacrylate) substrates and the channel dimensions were measured. Laser micromachining was then used to fabricate an all-plastic personalized drug testing microfluidic platform called OncoSlice that is meant to find the optimal subset of therapies specific for individual cancer patients. The device was composed of a 40-well plate that holds drugs and a channel network layer that delivers drugs to tissue samples. Optimization of laser settings to fabricate these layers was performed and several methods for bonding these layers together were explored. A method that uses SL to print two materials together in a single print to create microchannels with integrated biosensors was also developed. Two resins were utilized: a microchannel resin and a biosensor resin. Both resins are based on poly(ethylene glycol) diacrylate polymerization chemistry. The biosensor resin was incorporated with biotinylated structures for biotin-binding assays. Three biosensor strips were printed within a microchannel and fluorescence microscopy was used to confirm the existence of biotin heads within the strips. The digital manufacturing techniques used in this research to build microfluidic devices illustrate that fabrication time and costs can be significantly reduced. As laser micromachining and 3D printing systems becoming increasingly more advanced, microfluidic devices will become less expensive and simpler and convenient to produce.