Multivortex micromixing: novel techniques using Dean flows for passive microfluidic mixing

Mixing of fluids at the microscale poses a variety of challenges, many of which arise from the fact that molecular diffusion is the dominant transport mechanism in the laminar flow regime. The unfavorable combination of low Reynolds numbers and high Péclet numbers implies that cumbersomely long microchannels are required to achieve efficient levels of micromixing. Although considerable progress has been made toward overcoming these limitations (e.g., exploiting chaotic effects), many techniques employ intricate 3-D flow networks whose complexity can make them difficult to build and operate. In this research, we show that enhanced micromixing can be achieved using topologically simple and easily fabricated planar 2-D microchannels by simply introducing curvature and changes in width in a prescribed manner. This is accomplished by harnessing a synergistic combination of (i) Dean vortices that arise in the vertical plane of curved channels as a consequence of an interplay between inertial, centrifugal, and viscous effects, and (ii) expansion vortices that arise in the horizontal plane due to an abrupt increase in a conduitâÂÂs cross-sectional area. We characterize these effects using top-view imaging of aqueous streams labeled with tracer dyes and confocal microscopy of aqueous fluorescent dye streams, and by observing binding interactions between an intercalating dye and double-stranded DNA. These mixing approaches are versatile, scalable, and can be straightforwardly integrated as generic components in a variety of lab-on-a-chip systems

Fabrication of masters for microfluidic devices using conventional printed circuit technology

The capability to easily and inexpensively fabricate microfluidic devices with negligible dependence on specialized laboratory equipment continues to be one of the primary forces driving the widespread use of plastic-based devices. These devices are typically produced as replicas of a rigid mold or master incorporating a negative image of the desired structures. The negative image is typically constructed from either thick photoresists or etched silicon substrates using conventional photolithographic fabrication processes. While these micromachining techniques are effective in constructing masters with micron-sized features, the need to produce masters rapidly in order to design, fabricate, and test microfluidic devices, is a major challenge in microfluidic technology. In this research, we use inexpensive photosensitized copper clad circuit board substrates to produce master molds using conventional printed circuit technology. The techniques provide the benefits of parallel fabrication associated with photolithography without the need for cleanroom facilities, thereby offering a degree of speed and simplicity that allows microfluidic master molds to be constructed in approximately 30 minutes in any laboratory. These techniques are used to produce a variety of microfluidic channel networks using PDMS (polydimethylsiloxane) and melt-processable plastic materials

Digital Microfluidics Sample Analyzer

Three innovations address the needs of the medical world with regard to microfluidic manipulation and testing of physiological samples in ways that can benefit point-of-care needs for patients such as premature infants, for which drawing of blood for continuous tests can be life-threatening in their own right, and for expedited results. A chip with sample injection elements, reservoirs (and waste), droplet formation structures, fluidic pathways, mixing areas, and optical detection sites, was fabricated to test the various components of the microfluidic platform, both individually and in integrated fashion. The droplet control system permits a user to control droplet microactuator system functions, such as droplet operations and detector operations. Also, the programming system allows a user to develop software routines for controlling droplet microactuator system functions, such as droplet operations and detector operations. A chip is incorporated into the system with a controller, a detector, input and output devices, and software. A novel filler fluid formulation is used for the transport of droplets with high protein concentrations. Novel assemblies for detection of photons from an on-chip droplet are present, as well as novel systems for conducting various assays, such as immunoassays and PCR (polymerase chain reaction). The lab-on-a-chip (a.k.a., lab-on-a-printed-circuit board) processes physiological samples and comprises a system for automated, multi-analyte measurements using sub-microliter samples of human serum. The invention also relates to a diagnostic chip and system including the chip that performs many of the routine operations of a central labbased chemistry analyzer, integrating, for example, colorimetric assays (e.g., for proteins), chemiluminescence/fluorescence assays (e.g., for enzymes, electrolytes, and gases), and/or conductometric assays (e.g., for hematocrit on plasma and whole blood) on a single chip platform

Droplet-Based Pyrosequencing Using Digital Microfluidics

The feasibility of implementing pyrosequencing chemistry within droplets using electrowetting-based digital microfluidics is reported. An array of electrodes patterned on a printed-circuit board was used to control the formation, transportation, merging, mixing, and splitting of submicroliter-sized droplets contained within an oil-filled chamber. A three-enzyme pyrosequencing protocol was implemented in which individual droplets contained enzymes, deoxyribonucleotide triphosphates (dNTPs), and DNA templates. The DNA templates were anchored to magnetic beads which enabled them to be thoroughly washed between nucleotide additions. Reagents and protocols were optimized to maximize signal over background, linearity of response, cycle efficiency, and wash efficiency. As an initial demonstration of feasibility, a portion of a 229 bp Candida parapsilosis template was sequenced using both a de novo protocol and a resequencing protocol. The resequencing protocol generated over 60 bp of sequence with 100% sequence accuracy based on raw pyrogram levels. Excellent linearity was observed for all of the homopolymers (two, three, or four nucleotides) contained in the C. parapsilosis sequence. With improvements in microfluidic design it is expected that longer reads, higher throughput, and improved process integration (i.e., “sample-to-sequence” capability) could eventually be achieved using this low-cost platform