Mezić Research Group

Dynamical Systems and Nonlinear Control Theory

  • Increase font size
  • Default font size
  • Decrease font size

Our approach to microfluidics

The science and art of microfluidics has been advanced substantially since its introduction in designs of inkjet printers (2; 3; 4). A particularly important set of applications of microfluidic technology is within fields of genomics, proteomics and medical diagnostics (5; 6; 7; 8).


In this context, a typical problem to be solved using a microfluidic device is that of introducing two or more (bio)chemical species, performing mixing operations for fast binding, separating the product from auxiliary material and transporting the product to the analysis stage where it is concentrated in a smaller volume for enhancement of signal. In fact, enabling such a set of operations at microscale is the basic premise of Micro Total Analysis Systems (μTAS)(9; 10). Following the design of large-scale biochemical processing units, separate designs arose for various stages of this process, where mixing, reaction, separation, concentration and detection are performed in separate microchambers or microchannels. This in turn necessitates development of pumps and valves that are integrated into the device at microscale and serve as transport and traffic control devices for shipment of particles and liquids from one component to another. However, the development of efficient pumps and valves has been the outstanding problem for microfluidic device development to date. A possible way to circumvent the necessity of multiple micropumps and microvalves is to design a device in which a basic operation set can be performed based on a software protocol in a single cell. This was anticipated by Muggleton (1): “Todays generation of microfluidic machines is designed to carry out a specific series of chemical reactions, but further flexibility could be added to this tool kit by developing what one might call a chemical Turing machine. The universal Turing machine, devised in 1936 by Alan Turing, was intended to mimic the pencil-and-paper operations of a mathematician. The chemical Turing machine would be a universal processor capable of performing a broad range of chemical operations on both the reagents available to it at the start and those chemicals it later generates. The machine would automatically prepare and test chemical compounds but it would also be programmable,thus allowing much the same flexibility as real chemist has in the lab.”


In the last decade, a number studies have been oriented toward the application of programmable protocols like those used in computer science to microfluidics in order to develop the universality aspect of the LoC devices ((33; 34) that are mainly designed to perform one specific operation like PCR ((35; 36)) or christal growth. Those devices are composed of several specific units like pumps, mixers, valves or storage cells. In (34) approach it is argued that, while the underlying Turing theory of universal computation provides computers with an underlying theory that guarantees universality, no such thing is available for Programmable Lab on a Chip devices (PLoC’s). We maintain that the underlying theory is that of controllability. In fact, Turing universality is a form of controllability for digital computing.


Our program embodying this idea has been the development of Microfluidic Universal Processing Units - μPU’s that perform separation, concentration, mixing and reaction operations together with transport within a single contiguous chamber (called universal unit) and we show an experimental example of such a device. Devices we have developed have physical actuation enabled by programmable Interdigitated Electrode Arrays(12), where different multifrequency protocols (13; 14; 15; 16) can be used to generate electric field that impart forces on particles and induce fluid flows within the μPU. In (17) we have shown that combined operations of concentration and mixing are possible in our device using a range of frequencies. We continue to develop a theory and practice of universal microfluidic processing units, including development of a rudimentary programming language for the devices and perform experi-ments showing the capability of executing sets of basic microfluidic operations in a single device. We have shown that the basic operations governing virtually every bioassay processing (separation, concentration, mixing, transport and reaction) can be performed inside a low-volume single unit using sequences of combinations of basic electromagnetic and hydrodynamic forces.

References
[1] Muggleton S.H. Nature 440,409-410 (2006).
[2] T.M. Squires and S.R. Quake, Reviews of Modern Physics 77,pp. 977-1026
(2005).
[3] G.M. Whitesides, Nature 442,pp. 368-373 (2006).
[4] D. Janasek, J. Franzke and A. Manz, Nature442, pp. 374-380 (2006).
[5] J. Wang, G. Sui, V.P. Mocharla, R.J. Lin, M.E. Phelps, H.C. Kolb and H.R. Tseng, Lab-on-a-Chip 45,pp. 5276-5281 (2006).
[6] P. Yager, T. Edwards, E. Fu, K. Helton, K. Nelson, M.R. Tam and B.H. Weigl, Nature 442, pp. 412-418 (2006).
[7] E.P. Kartalov, J.F. Zhong, A. Scherer, S.R. Quake, C.R. Taylor and W.F. Anderson, Biotechniques A, 40, 85-90, (2006). 10945 (2002).
[8] C.D. Chin, V. Linderb, S.K. Sia, lab on a Chip 7,pp. 41-57 (2007).
[9] A. Manz, N. Graber and H.M. Widmer, Sensors and Actuators BChemical
1,pp. 1-6 (1990).
[10] P.S. Dittrich, K. Tachikawa and A. Manz, Analytical Chemistry78, pp. 3887-3907 (2006).
[11] J. von Neumman, Report on the Contract No. W-670-ORD-4926, Between the United States Army Ordnance Department and the University of Pennsylvania Moore School of Electrical Engineering (1945).
[12] P.R.C. Gascoyne, Y. Huang and R. Pethig, J. Vyoukal and F.F. Becker, IEEE Engineering in Biology and Medicine Magazine 22, pp. 43-50 (2003).
[13] R. Pethig, M.S. Talary and R.S. Lee, Measurement Science and Technology, 3, 439-445 (1992).
[14] D.E. Chang, S. Loire and I. Mezic, Proceedings of the Conference on Decision and Control (2003).
[15] S. Loire, Y.T. Zhang, F. Bottausci, I. Mezic and N.C. MacDonald, Proceedings of the NSTI-Nanotech 2005 (2005).
[16] S. Loire and I. Mezic, Proceedings of the Conference on Decision and Control (2003).
[17] I. Tuval, I. Mezic, O. Piro, Y. Zhang, F. Bottausci and N. MacDonald, Physical Review Letters 95, 236002 (2007).
[18] A. Ramos, H. Morgan, H. Green and A. Castellanos, J. Phys. D: Appl. Phys. 31,pp. 2238-2353 (1998).
[19] A. Ramos, H. Morgan, H. Green and A. Castellanos, Journal of Colloid and Interface Science 217,pp. 420-422 (1999).
[20] T.M. Squires and M.Z. Bazant, Journal of Fluid Mechanics 509,pp. 217- 152 (2004).
[21] M.S. Kilic, M.Z. Bazant and A. Adjari, Physical Review Letters 75, 021502 (2007).
[22] N. Gadish and J. Voldman, Analytical Chemistry 78,pp. 7870-7876 (2006).
[23] T.B. Jones, Electromechanics of particles, Edited by Cambridge University Press, New York (1995).
[24] M.P. Hughes, Nanoelectromechanics in engineering and biology, Edited by CRC Press, Boca Raton (2003).
[25] T.H. Solomon and I. Mezic, Nature 425,pp. 376-380 (2003). 3696 (1983).
[26] A.‘Gonzalez, A. Ramos, H. Morgan, N.G. Green and A. Castellanos, Jour-
nal of Fluid Mechanics, 564 pp. 415-433. (2006).
[27] H. Aref, Journal of Fluid Mechanics 143, pp. 1-21 (1984).
[28] M. Volpert, I. Mezic, C.D. Meinhart and M. Dahleh, Proceedings of the ASME Mechanical engineering International Congress and Exposition, MEMS, Nashville, TN , pp. 483-487 (1999).
[29] A.D. Stroock, S.K.W. Dertinger, A. Ajdari, I. Mezic, H.A. Stone and G.M. Whitesides, Science 295, pp. 647-651 (2002).
[30] D. D’Alessandro, M. Dahleh and I. Mezic, IEEE Transactions on Automatic Control 44,pp. 1852-1863 (1999).
[31] J. Evans, D. Liepmann and A.P. Pisano, Planar laminar mixer, edited in the 10th Annual Workshop of Micro Electro Mechanical System, Nagoya, Japan, pp. 96-101 (1997).
[32] T. Thorsen, S.J. Maerkl and S.R. Quake, Science 298,pp. 280-284 (2002).
[33] W. Thies, J.P. Urbanski, T. Thorsten and S. Amarasinghe, Natural Com-
puting, pp.308-323 (2006).
[34] A.M. Amin, M. Thottethodi, T.N. Vijaykumar,S. Wereley and S.C. Jacobson, International symposium on computer architecture, June 9-13, San Diego, CA, pp 254-265.
[35] E.T. Lagally,J.R. Scherer, R.G. Blazej, N.M. Toriello, B.A. Diep, M. Ramchandani ,G.F. Sensabaugh, L.W. Riley, R.A. Mathies, Anal Chem 76(11) pp.3162-70 (2004).
[36] C. L. Hansen, E. Skordalakes , J. M. Berger , and S. R. Quake, Proc. Nat’l Acad. Sci. 99 pp. 16531-6 (2002).
Last Updated on Tuesday, 02 July 2013 16:11  

Acknowledgements