Microfluidics

Microfluidics deals with the behavior, precise control and manipulation of fluids that are geometrically constrained to a small, typically sub-milimetre, scale. It is a multidisciplinary field intersecting engineering, physics, chemistry, microtechnology and biotechnology, with practical applications to the design of systems in which such small volumes of fluids will be used. Microfluidics has emerged in the beginning of the 1980s and is used in the development of inkjet printheads, DNA chips, lab-on-a-chip technology, micro-propulsion, and micro-thermal technologies.

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Microscale behavior of fluids

The behavior of fluids at the microscale can differ from 'macrofluidic' behavior in that factors such as surface tension, energy dissipation, and fluidic resistance start to dominate the system. Microfluidics studies how these behaviors change, and how they can be worked around, or exploited for new uses.

At small scales (channel diameters of around 100 nanometers to several hundred micrometers) some interesting and unintuitive properties appear. The Reynolds number, which characterizes the presence of turbulent flow, is extremely low, thus the flow will remain laminar. Thus, two fluids joining will not mix readily via turbulence, so diffusion alone must cause the two fluids to mingle.

Key application areas

Microfluidic structures include on one hand micropneumatic systems, i.e. microsystems for the handling of off-chip fluids (liquid pumps, gas valves, etc), and on the other hands microfluidic structures for the on-chip handling of nano- and picolitre volumes. The commercially most successful application today is the inkjet printhead.

Advances in microfluidics technology are revolutionizing molecular biology procedures for enzymatic analysis (e.g., glucose and lactate assays), DNA analysis (e.g., polymerase chain reaction and high-throughput sequencing), and proteomics. The basic idea of microfluidic biochips is to integrate assay operations such as detection, as well as sample pre-treatment and sample preparation on one chip.

An emerging application area for biochips is clinical pathology, especially the immediate point-of-care diagnosis of diseases. In addition, microfluidics-based devices, capable of continuous sampling and real-time testing of air/water samples for biochemical toxins and other dangerous pathogens, can serve as an always-on "bio-smoke alarm" for early warning.

Continuous-flow microfluidics

These technologies are based on the manipulation of continuous liquid flow through microfabricated channels. Actuation of liquid flow is implemented either by external pressure sources, external mechanical pumps, integrated mechanical micropumps, or by electrokinetic mechanisms. Continuous-flow microfluidic operation is the mainstream approach because it is easy to implement and less sensitive to protein fouling problems. Continuous-flow devices are adequate for many well-defined and simple biochemical applications, and for certain tasks such as chemical separation, but they are less suitable for tasks requiring a high degree of flexibility or complicated fluid manipulations. These closed-channel systems are inherently difficult to integrate and scale because the parameters that govern flow field vary along the flow path making the fluid flow at any one location dependent on the properties of the entire system. Permanently-etched microstructures also lead to limited reconfigurability and poor fault tolerance capability.

Process monitoring capabilities in continuous-flow systems can be achieved with highly sensitive microfluidic flow sensors based on MEMS technology which offer resolutions down to the nano litre range.

Digital (droplet-based) microfluidics

Alternatives to the above closed-channel continuous-flow systems include novel open structures, where discrete, independently controllable droplets are manipulated on a substrate. Following the analogy of microelectronics, this approach is referred to as digital microfluidics. By using discrete unit-volume droplets, a microfluidic function can be reduced to a set of repeated basic operations, i.e., moving one unit of fluid over one unit of distance. This "digitization" method facilitates the use of a hierarchical and cell-based approach for microfluidic biochip design. Therefore, digital microfluidics offers a flexible and scalable system architecture as well as high fault-tolerance capability. Moreover, because each droplet can be controlled independently, these systems also have dynamic reconfigurability, whereby groups of unit cells in a microfluidic array can be reconfigured to change their functionality during the concurrent execution of a set of bioassays. One common actuation method for digital microfluidics is electrowetting-on-dielectric (EWOD). One limiting factor for applying EWOD to biological samples is the surface fouling due to proteins severely damages the controllability of droplets. Another recently developed technology is based on acoustically induced droplet transport employing Surface Acoustic Waves.

DNA chips (microarrays)

Early biochips were based on the concept of a DNA microarray, e.g., the GeneChip DNAarray from Affymetrix, which is a piece of glass, plastic or silicon substrate on which pieces of DNA (probes) are affixed in a microscopic array. Similar to a DNA microarray, a protein array is a miniature array where a multitude of different capture agents, most frequently monoclonal antibodies, are deposited on a chip surface; they are used to determine the presence and/or amount of proteins in biological samples, e.g., blood. A drawback of DNA and protein arrays is that they are neither reconfigurable nor scalable after manufacture.

Acoustic droplet ejection (ADE)

Acoustic droplet ejection uses a pulse of ultrasound to move low volumes of fluids (typically nanoliters or picoliters) without any physical contact. This technology focuses acoustic energy into a fluid sample in order to eject droplets as small as a millionth of a millionth of a liter (picoliter = 10^-12 liter). ADE technology is a very gentle process, and it can be used to transfer proteins, high molecular weight DNA and live cells without damage or loss of viability. This feature makes the technology suitable for a wide variety of applications including proteomics and cell-based assays.

Fuel cells

Microfluidic fuel cells can use laminar flow to separate the fuel and its oxidant to control the interaction of the two fluids without a physical barrier as would be required in conventional fuel cells. See J. Am. Chem. Soc. (2005)

• Water Management in PEM Fuel Cells

• Building a Better Fuel Cell Using Microfluidics

• Fuel Cell Initiative at MnIT Microfluidics Laboratory

External information

• μFluids@Home (Distributed Computing Project)
• Biomicrofluidics, an open-source peer-reviewed journal published by the American Institute of Physics

Tutorials and summaries

• MIFLUS - Microfluidics Terminology tree
• Living La Vida LOC(a): A Brief Insight into the World of "Lab on a Chip" and Microfluidics - A review from the Science Creative Quarterly

Conference and journal papers

• H. Gau, S. Herminghaus, P. Lenz, R. Lipowsky, "Liquid Morphologies on Structured Surfaces: From Microchannels to Microchips", Science (283), 1999
• M. G. Pollack, R. B. Fair and A. D. Shenderov, "Electrowetting-based actuation of liquid droplets for microfluidic applications", Applied Physics Letters, vol. 77, pp. 1725-1726, 2000
• T. Thorsen, S. Maerkl and S. Quake, "Microfluidic large-scale integration", Science, vol. 298, pp. 580-584, 2002
• E. Verpoorte and N. F. De Rooij, "Microfluidics meets MEMS", Proceedings of the IEEE, vol. 91, pp. 930-953, 2003
• F. Su and K. Chakrabarty, "Unified high-level synthesis and module placement for defect-tolerant microfluidic biochips", Proc. IEEE/ACM Design Automation Conference, pp. 825-830, 2005
• K. Chakrabarty and J. Zeng, "Design automation for microfluidics-based biochips", ACM Journal on Emerging Technologies in Computing Systems, vol. 1, pp. 186-223, December 2005
• C. Priest, S. Herminghaus, and R. Seemann, "Generation of Monodisperse Gel Emulsions in a Microfluidic Device", Appl. Phys. Lett. (88), 2006

Books

• Nguyen, N. T.; S. T. Wereley (2006). Fundamentals and Applications of Microfluidics, 2nd ed, Artech House. ISBN 1-58053-972-6. 
• (2004) in Geschke, Klank & Telleman, eds.: Microsystem Engineering of Lab-on-a-chip Devices, 1st ed, John Wiley & Sons. ISBN 3-527-30733-8. 
• (2005) in J. P. Kutter and Y. Fintschenko, eds.: Separation Methods In Microanalytical Systems. CRC Press. ISBN 0-8247-2530-1. 

• (2003) in Oosterbroek & van den Berg, eds.: Lab-on-a-Chip. Elsevier. ISBN 0-444-51100-8. 
• (1999) in Manz & Becker, eds.: Microsystem Technology in Chemistry and Life Sciences. Springer. ISBN 3-540-65555-7. 
• Zhang, T.; K. Chakrabarty, R. B. Fair (2002). Microelectrofluidic Systems: Modeling and Simulation. CRC Press. ISBN 0-8493-1276-0. 
• Saliterman, S (2006). Fundamentals of BioMEMS and Medical Microdevices. SPIE. ISBN 0-8194-5977-1. 
• Tabeling, P (2006). Introduction to Microfluidics. Oxford University Press. ISBN 0-19-856864-9. 
• Wilkes, J.O. (2005). Fluid Mechanics for Chemical Engineers with Microfluidics and CFD, 2nd ed, Prentice Hall. ISBN 0-13-148212-2. 
• Bruus, Henrik (2007). Theoretical Microfluidics. Oxford University Press. ISBN-13 978-0199235094.