On-Chip Sample Preparation with Multiple Dilutions Using Digital Microfluidics

In many biochemical protocols, solution preparation is a preprocessing step for mixing two or more fluids in a given ratio. Dilution of a biochemical sample/reagent is the special case of mixing or solution preparation where only two different type of fluids, one of which is a buffer solution, are mixed at a certain ratio corresponding to the desired concentration factor. Bioassays implemented on digital micro fluidic biochips may require several different concentration values of the same sample/reagent. In this paper, we present a scheme in which a set of different target droplets (with concentration values ranged between 0% and 100%) can be produced with an acceptable error bound in minimum mix-split steps. The method does not require any intermediate storage since, at each step, the current droplet is mixed only with the sample (with 100% concentration) or with the buffer (with 0% concentration) droplet. The problem of generating multiple target concentrations has been formulated based on a binary de Bruijn graph. The proposed technique outperforms the existing single target based methods in terms of both the number of mix-split steps and the number of waste droplets. This in turn, reduces the execution time, the number of electrode actuations, and sample/reagent requirement. A digital micro fluidic platform can also be easily designed to implement such on-chip sample preparation.

[1]  Krishnendu Chakrabarty,et al.  Optimization of Dilution and Mixing of Biochemical Samples Using Digital Microfluidic Biochips , 2010, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.

[2]  Krishnendu Chakrabarty,et al.  Waste-aware dilution and mixing of biochemical samples with digital microfluidic biochips , 2011, 2011 Design, Automation & Test in Europe.

[3]  R. Fair,et al.  Droplet-based microfluidic lab-on-a-chip for glucose detection , 2004 .

[4]  Flavio D'Alessandro.  A combinatorial problem on Trapezoidal words , 2002, Theor. Comput. Sci..

[5]  Avraham Rasooly,et al.  Fabrication and microfluidics , 2009 .

[6]  Aaron R. Wheeler,et al.  Digital bioanalysis , 2009, Analytical and bioanalytical chemistry.

[7]  Jack Zhou,et al.  Chemical and Biological Applications of Digital-Microfluidic Devices , 2007, IEEE Design & Test of Computers.

[8]  Dhiraj K. Pradhan,et al.  A Fault-Tolerant Communication Architecture for Distributed Systems , 1982, IEEE Transactions on Computers.

[9]  Andrew B. Kahng,et al.  Match twice and stitch: a new TSP tour construction heuristic , 2004, Oper. Res. Lett..

[10]  K. Chakrabarty,et al.  On-chip biochemical sample preparation using digital microfluidics , 2011, 2011 IEEE Biomedical Circuits and Systems Conference (BioCAS).

[11]  Narsingh Deo,et al.  Graph Theory with Applications to Engineering and Computer Science , 1975, Networks.

[12]  S Roy,et al.  Layout-Aware Solution Preparation for Biochemical Analysis on a Digital Microfluidic Biochip , 2011, 2011 24th Internatioal Conference on VLSI Design.

[13]  A. Wheeler,et al.  Let's get digital: digitizing chemical biology with microfluidics. , 2010, Current opinion in chemical biology.

[14]  N.R. Malik,et al.  Graph theory with applications to engineering and computer science , 1975, Proceedings of the IEEE.

[15]  Eleanor A. M. Graham.  Lab-on-a-chip technology , 2005, Forensic science, medicine, and pathology.

[16]  de Ng Dick Bruijn.  A combinatorial problem , 1946 .

[17]  G I INGRAM.  A note on dilution systems. , 1962, Immunology.

[18]  William Thies,et al.  Abstraction layers for scalable microfluidic biocomputing , 2008, Natural Computing.

[19]  Tao Xu,et al.  Automated, accurate, and inexpensive solution-preparation on a digital microfluidic biochip , 2008, 2008 IEEE Biomedical Circuits and Systems Conference.

[20]  Fred W. Glover,et al.  Construction heuristics for the asymmetric TSP , 2001, Eur. J. Oper. Res..

[21]  Chang-Biau Yang,et al.  Shortest path routing and fault-tolerant routing on de Bruijn networks , 2000 .

[22]  Kristi S. Anseth,et al.  3D Polymeric Microfluidic Device Fabrication via Contact Liquid Photolithographic Polymerization (CLiPP) , 2006 .

[23]  K. Oh,et al.  Generalized serial dilution module for monotonic and arbitrary microfluidic gradient generators. , 2009, Lab on a chip.

[24]  Krishnendu Chakrabarty,et al.  Digital Microfluidic Biochips - Design Automation and Optimization , 2010 .

[25]  Pavel A Pevzner,et al.  How to apply de Bruijn graphs to genome assembly. , 2011, Nature biotechnology.

[26]  Mark K. Goldberg,et al.  Performance Characterization of a Reconfigurable Planar-Array Digital Microfluidic System , 2006, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.

[27]  R. Jonker,et al.  Transforming asymmetric into symmetric traveling salesman problems , 1983 .