Cambridge University Press 978-0-521-86025-3 - Electrokinetically Driven Microfluidics and Nanofluidics Hsueh-Chia Chang and Leslie Y. Yeo Excerpt More information 1 Introduction and Fundamental Concepts 1.1 Electrokinetic Mechanisms for Microfluidic and Nanofluidic Transport 1.1.1 Introduction to Microfluidic and Nanofluidic Systems The enormous potential of microscale and nanoscale technology for chemical and biological analysis is reflected by the recent explosive growth in research on laboratory-on-a-chip and miniature diagnostic devices (van den Berg and Harrison, 1998; Manz and Becker, 1998). An example of such a device is depicted in Fig. 1.1. Advances in microfabrication, nanofabrication and microelectromechanical systems (MEMS) over the past few decades has allowed miniaturized devices of growing complexity and sophistication to be developed for various applications, in partic- ular, for the biomedical and pharmaceutical industries. Microchip devices have already been developed for drug screening, electrochemical immunoassays, drug delivery, point-of-care medical diagnostics, bacteria detection, flow cytometry (e.g., cell culture and manipulation), proteomics, genomics (e.g., polymerase chain reac- tion, or DNA sizing and sequencing), environmental monitoring, and the detection of explosives and biological warfare agents, among others. Although commercially successful devices have just begun to appear, it is anticipated that they will spur new biotechnologies in the next decade. The ability to miniaturize, automate, and parallelize large-scale batch processes represents a distinct advantage that not only reduces the amount of expensive sam- ples and reagents used but also allows the process to be carried out at a fraction of the cost and duration as a result of shorter residence, reaction, and response times. Although high-throughput production is probably unlikely with microdevices, the production rate is nevertheless higher than that of batch processes of similar dimen- sions, particularly if continuous and parallel-chip structures are used. Such mas- sively parallel chips that operate with small-volume samples are intended for gene sequencing, proteomics, drug development, antibiotic screening, and other labora- tory processes. The same microfluidic technologies for transporting fluids in small devices may also find applications in portable direct-methanol fuel cells and future microscale versions of such battery-replacement technology. 1 © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-86025-3 - Electrokinetically Driven Microfluidics and Nanofluidics Hsueh-Chia Chang and Leslie Y. Yeo Excerpt More information 2 Introduction and Fundamental Concepts Sample Flow loading metering Mixing Reaction Separation Detection Sample inlets Electrokinetic pumps Photodetector or Air purge Optical sensor Manifold or Microvalves Separator or Micromixer Chromatographic Sample Thermal Reactor column outlet Figure 1.1. Schematic illustration of an integrated laboratory-on-a-chip device to perform scaled-down biological and chemical analyses involving flow metering, mixing, reaction, sep- aration, and detection. We believe, however, that miniaturized diagnostics will constitute the most commercially relevant development among the entire range of microfluidic devices. Rapid and portable integrated miniature diagnostic kits that do not require lab- oratory equipment and trained technicians are extremely attractive to the med- ical, antiterrorism, environmental, and animal-care diagnostic industries. Specifi- cally, future multiplexed miniature diagnostic kits will use antibody functionalized immunobeads for pathogen detection and DNA probe functionalized genetic beads for DNA identification. Such bead-based diagnostic kits probably will not be able to compete with hybridization microarrays in terms of library volume (target number). However, microfluidic devices, in particular, those driven by electrokinetics, with the ability to manipulate these nanocolloids at the microscale level, have response times that are orders of magnitude faster. In these instances, the transport limita- tions for any docking event will be reduced by the shear number of nanocolloids and by the judicious application of electrokinetic forces, delivered by microelec- trodes and nanoelectrodes, on the colloids. The colloids offer an overall surface area that is orders of magnitude larger than that of a microarray pixel or even that of a microfluidic channel. They can hence capture all the targets and, if the detection is carried out with fluorophores on the targets or with other target-labeled reporters, can provide significantly lower detection thresholds than those obtained with cur- rent microarray technology. Diagnostic bead assays, like all other surface assays, involve several steps of mixing, rinsing, and hybridization. The beads can be transported from one reservoir to the next on the chip for such multiplex operations, or they can be confined to one reservoir and the rinsing–hybridization buffer is pumped through the reservoir. A combination of these two strategies can also be used. There is therefore a need to develop bead manipulation as well as fluid transport and metering platforms. Chip- based membranes that can confine or trap these beads may also be necessary, but such membranes tend to produce large hydrodynamic resistance (pressure drop) and require high pressures above those accessible by micropumps. Electrokinetic bead traps or filters, on the other hand, do not produce such significant pressure drops and are hence much more desirable. © in this web service Cambridge University Press www.cambridge.org Cambridge University Press 978-0-521-86025-3 - Electrokinetically Driven Microfluidics and Nanofluidics Hsueh-Chia Chang and Leslie Y. Yeo Excerpt More information 1.1 Electrokinetic Mechanisms for Microfluidic and Nanofluidic Transport 3 Strategies are subsequently required for detecting the molecules, pathogens, or other organisms that have docked onto the beads. Currently, bead-based and other surface assays utilize optical-detection methods, similar to those used in cytometry. However, optical detection may not be the most robust technique for incorporation into chip-based devices, particularly if they require elaborate optical-detection facil- ities such as confocal microscopy. Although on-chip light sources, waveguides, and optical sensors are currently being developed, we envisage that these will remain expensive within the near future and incompatible with the concept of disposable chips – the devices require rinsing for reuse, which would typically render on-chip optical sensing impractical or commercially unfeasible. Electrical impedance sens- ing, with bare electrodes or electrodes functionalized with chemical or molecular probes, on the other hand, may prove to be significantly more practical, as it does not require fluorophore tagging and optical-detection schemes. In addition, electri- cal impedance sensing is perhaps most effective for nanocolloidal systems because the impedance signature of the colloids is sensitive to surface molecular-docking events. Significant efforts are currently underway in electrode functionalization and material synthesis to enhance selective molecular or colloidal docking. Whatever the detection method, microfluidic devices have the ability to trap these colloidal particles or beads for sensitivity enhancement in immunoassay diag- nostic testing. The precision offered by such devices is also driving an emerging field in microfluidics, namely the synthesis of nanotextured materials, biological mem- branes, and biofilms. The microdevices allow self-assembly or directed-assembly of inorganic or biological materials one filament and one layer at a time by means of a modular and sequential assembly process at the molecular level. Designed com- plex structures with rich morphologies beyond spontaneous and uncontrolled self- assembly processes are the targets of such microfluidic material synthesis. At the very heart of these devices is core microfluidic technology that is indispensable to its operation, consisting of a set of integrated components that are required to actuate, regulate, mix, manipulate, separate, and detect the sam- ples, reagents, and biological species involved. These components comprise pumps, valves, mixers, separators, and sensors fabricated onto a microchip and connected by a series of small capillary channels. Typically, the characteristic length scale L of these components and the channels range between 1 and 102 µm. Because the surface-area-to-volume ratio increases inversely proportional to L, interfacial effects become dominant at these small length scales. Although the large surface- area-to-volume ratio provides significant advantages over macroscopic flows such as enhanced heat and mass transfer and small sample volumes, the design of microflu- idic devices requires proper consideration of the associated interfacial phenomena. For example, microscopic effects such as disjoining pressure and wall slip or wall shear present significant design challenges in the scale down to dimensions commen- surate with microfluidic devices. These effects become more acute when nanocol- loids are used – not only is the surface-area-to-volume ratio even larger in these sys- tems, new physical phenomena that are foreign to substrate assays are also observed when the colloid sizes approach molecular and electrical Debye double layer (thin region close to the surface in which