Mark Eddings

Determining the optimal PDMS–PDMS bonding technique for microfluidic devices

A number of polydimethysiloxane (PDMS) bonding techniques have been reported in the literature over the last several years as the focus on multilayer PDMS microfluidic devices has increased. Oxygen plasma bonding, despite cost, additional fabrication time and inconsistent bonding results, has remained a widely used method for bonding PDMS layers. A comparative study of four rapid, inexpensive alternative PDMS?PDMS bonding approaches was undertaken to determine relative bond strength. These include corona discharge, partial curing, cross-linker variation and uncured PDMS adhesive. Partial curing and uncured PDMS adhesive demonstrated a considerable improvement in bond strength and consistency by retaining average bond strengths of over 600 kPa, which was more than double the average bond strength of oxygen plasma. A description of each technique and their performance relative to oxygen plasma bonding is included.

A PDMS-based gas permeation pump for on-chip fluid handling in microfluidic devices

We demonstrate a non-contact pumping mechanism for the manipulation of aqueous solutions within microfluidic devices. The method utilizes multi-layer soft lithography techniques to integrate a thin polydimethylsiloxane (PDMS) membrane that acts as a diffusion medium for regulated air pressure and a vacuum. Pressurized microchannels filter air through the PDMS membrane due to its high gas permeability causing a pressure difference in the liquid channel and generating flow. Likewise, a vacuum can be applied to pull air through the membrane allowing the filling of dead-end channels and the removal of bubbles. Flow rates vary according to applied pressure/vacuum, membrane thickness and diffusion area. A gas permeation pump is an inexpensive alternative to other micropumps. The pump is easily integrated with highly arrayed multi-channel/chamber applications for micro-total analysis systems, fluid metering and dispensing, and drug delivery. Flow rates of 200 nl min−1 have been achieved using this technique. Successful localized fluid turning at intersections, fluid metering and filling of dead-end chambers were also demonstrated.

Bubble inclusion and removal using PDMS membrane-based gas permeation for applications in pumping, valving and mixing in microfluidic devices

Several advancements in fluid handling applications of a gas-permeable polydimethylsiloxane (PDMS) membrane are demonstrated. Devices for controlled pumping, bubble injection, bubble removal and mixing are demonstrated using a three-layered fabrication method. The ability of a gas-permeable membrane to control flow in glass channels is determined. Consistent flow rates ranging from approximately 1 to 14 µl min−1 were observed using control pressures from 100 to 700 mbar. Bubble injection and removal from microfluidic channels was performed in monolithic PDMS devices using several bubble trap geometries at fluid flow rates over 100 µl min−1. The rate of removal of the air in the bubble trap was determined as a function of the area of membrane exposed and the applied vacuum. The PDMS membrane was shown to be an effective tool for the injection and removal of air bubbles in a method of enhancing mixing using bubbles and branched microchannels. The amount of mixing was optically determined before and after bubbles entered the fluid channel. The ability to produce all of these compatible components using a single fabrication process is a step toward inexpensive, parallel, highly integrated microfluidic systems with minimal external controls.

In situ microarray fabrication and analysis using a microfluidic flow cell array integrated with surface plasmon resonance microscopy

Surface Plasmon Resonance Microscopy (SPRM) is a promising label-free analytical tool for the real-time study of biomolecule interactions in a microarray format. However, flow cell design and microarray fabrication have hindered throughput and limited applications of SPRM. Here we report the integration of a microfluidic flow cell array (MFCA) with SPRM enabling in situ microarray fabrication and multichannel analysis of biomolecule probe-target interactions. We demonstrate the use of the MFCA for delivery of sample solutions with continuous flow in 24 channels in parallel for rapid microarray creation and binding analysis while using SPRM for real-time monitoring of these processes. Label-free measurement of antibody-antibody interactions demonstrates the capabilities of the integrated MFCA-SPRM system and establishes the first steps of the development of a high-throughput, label-free immunogenicity assay. After in situ probe antibody immobilization, target antibody binding was monitored in real time in 24 channels simultaneously. The limit of detection for this particular antibody pair is 80 ng/mL which is approximately 6 times lower than the industry recommended immunogenicity assay detection limit. The integrated MFCA-SPRM system is a powerful and versatile combination for a range of array-based analyses, including biomarker screening and drug discovery.

Reusable electrochemical cell for rapid separation of [18F]fluoride from [18O]water for flow-through synthesis of 18F-labeled tracers

A brass-platinum electrochemical micro-flow cell was developed to extract [(18)F]fluoride from an aqueous solution and release it into an organic-based solution, suitable for subsequent radio-synthesis, in a fast and reliable manner. This cell does not suffer electrode erosion and is thus reusable while operating faster by enabling increased voltages. By optimizing temperature, trapping and release potentials, flow rates, and electrode materials, an overall [(18)F]fluoride trapping and release efficiency of 84 ± 5% (n=7) was achieved. X-ray photoelectron spectroscopy (XPS) was used to analyze electrode surfaces of various metal-metal systems and the findings were correlated with the performance of the electrochemical cell. To demonstrate the reactivity of the released [(18)F]fluoride, the cell was coupled to a flow-through reactor and automated synthesis of [(18)F]FDG with a repeatable decay-corrected yield of 56 ± 4% (n=4) was completed in < 15 min. A multi-human dose of 5.92GBq [(18)F]FDG was also demonstrated.

Improved continuous-flow print head for micro-array deposition

Limitations in depositing ligands using conventional micro-array pin spotting have hindered the application of surface plasmon resonance imaging (SPRi) technology. To address these challenges we introduce a modification to our continuous-flow micro-spotting technology that improves ligand deposition. Using Flexchip protein A/G and neutravidin capturing surfaces, we demonstrate that our new microfluidic spotter requires 1000 times less concentrated antibodies and biotinylated ligands than is required for pin spotting. By varying the deposition flow rate, we show that the design of our tip overlay flow cell is efficient at delivering sample to the substrate surface. Finally, contact time studies show that it is possible to capture antibodies and biotinylated ligands at concentrations of less than 0.1 ug/ml and 100 pM, respectively. These improvements in spotting technology will help to expand the applications of SPRi systems in areas such as antibody screening, carbohydrate arrays, and biomarker detection.

A Hands-On Freshman Survey Course to Steer Undergraduates Into Microsystems Coursework and Research

Full class loads and inflexible schedules can be a significant obstacle in the implementation of freshman survey courses designed to guide engineering students into emerging research areas such as micro- and nanosystems. A hands-on, interactive course was developed to excite freshmen early in their engineering program to pursue research and careers in microsystems. The course focused on the top-down and bottom-up approaches to building devices, including the metrology tools required for visualization and characterization at the micro- and nanoscales. Modular lab components required students to interact with, build, and characterize microsystems. Macroscale versions were used to teach microscale concepts. An introductory module included dissecting the iPod Mp3 player, understanding its macroscale components and inspecting the microscale components in optical and scanning electron microscopes (SEM). A summary of the class focus and lab exercise modules is reported.

Low-Cost MEMS Technologies

Many researchers and companies are seeking methods to overcome the high cost of traditional microfabrication methods. This chapter presents various methods for performing common microfabrication tasks using relatively low-cost methods. The chapter discusses these low-cost methods in four sections. Section 1.12.2 discusses inexpensive techniques for use with photolithography such as low-cost mask fabrication techniques and the use of photopatternable polymers. Section 1.12.3 discusses replacements for photolithography such as xurography, lamination, screen printing, and stamping. Section 1.12.4 focuses on the low-cost methods for rapid prototyping such as soft lithography and powder blasting. Section 1.12.5 discusses methods for low-cost manufacturing of microelectromechanical systems (MEMS) devices with a focus on molding and embossing methods. Overall, low-cost methods are found to compete well with traditional MEMS methods, especially in biomedical and microfluidic applications.