- The overall concept of reducing laboratory operations to a scale that fits on a single microfluidic chip has been an attractive area of research over the last several decades. Despite a surge in research, few commercial success stories have been written. Lab-on-a-chip technologies have the capability to be cost effective due to reduced reagent consumption, offer shorter analysis times due to their small scale, i.e. path lengths, and have the ability to work with decreased sample sizes. Due to these benefits, microfluidic devices show great promise as point-of-care devices for the analysis of biologically relevant analytes as they are inherently compact, have the potential to be produced at low-cost, and can be manufactured out of materials that allow for single-use followed by responsible disposal. In this work, a series of new fabrication techniques for low-cost microfluidic platforms in both capillary-driven (wicking) and pressure-driven platforms as well as their potential applications in low-cost clinical chemistry analysis are explored.
In the first component of this research effort a new method of fabricating microfluidic paper-based analytical devices (µPADs) using aerosolized deposition of polycaprolactone (PCL) was developed. PCL is a biodegradable, semicrystalline polyester with excellent thermal properties including a glass transition temperature (T[subscript g]) of -60 ˚C and a melting point of 60 ˚C. Hydrophilic substrates were masked with low-adhesive painter’s tape and PCL was applied using an airbrush to create capillary-driven microfluidic devices. With this approach, the traditional fabrication processes used for manufacturing µPADs have been simplified allowing rapid, low-cost fabrication of µPADs with hydrophilic features as small as 480 µm, and hydrophobic barriers as small as 260 µm. Point-of-care applications involving enzymatic determination of glucose and chemical determination of protein concentration were successfully demonstrated.
The second portion of this research involved the development of a smartphone (iOS) application for conducting colorimetric analysis of µPADs. The application, OccuChrome, was created as a capstone project with the School of Electrical Engineering and Computer Science at Oregon State University. OccuChrome was designed to allow all aspects of colorimetric analysis including model development, calibration curve development, unknown analysis, and results sharing on a single platform. Results obtained from OccuChrome compared favorably with those obtained using traditional colorimetric image analysis via ImageJ.
The next stage of work explored the application of PCL saturated paper as a low-cost material for the fabrication of open channel microfluidic devices in both pressure-driven and capillary-driven formats. The favorable thermal properties of PCL, namely the low T[subscript g] and low T[subscript m] allow for easy fabrication using a simple method of cut and stack lamination to assemble both 2D and 3D microfluidic devices. A variety of bonding techniques including microwave adhesion and laser welding were explored as alternatives to thermal lamination. The classic diffusion limited laminar flow of two miscible solutions observed in traditional open-channel microfluidic devices was able to be replicated. Other pressure-driven microfluidic applications including passive mixing, droplet generators, and serial dilution generators were also demonstrated in this low-cost platform. Despite being composed primarily of high porosity material; these devices were able to operate under normal conditions for hours without leaking so long as a maximum operating pressure of ~1.2 psi is maintained.
The final stage of work involved the development of PCL saturated paper hybrid microfluidic devices, that is devices consisting of both open channel and paper wicking regions. Creatinine and urea assays were developed using creatinine deiminase and urease for the in-situ generation of NH₃ as a product. Using one of the unique properties of PCL saturated paper, gas permeability, the enzymatic reaction is able to be separated from the detection reaction allowing simple pH indicators to be used for the detection of gaseous NH₃. Reaction conditions were optimized to increase the percentage of volatile NH₃ generated via the enzymatic processes in an effort to decrease the overall assay time. It was experimentally determined that a pH of ~10 was ideal to increase the relative NH3 concentration without impairing the enzyme activity.