High-throughput flow alignment of barcoded hydrogel microparticles.

Suspension (particle-based) arrays offer several advantages over conventional planar arrays in the detection and quantification of biomolecules, including the use of smaller sample volumes, more favorable probe-target binding kinetics, and rapid probe-set modification. We present a microfluidic system for the rapid alignment of multifunctional hydrogel microparticles designed to bear one or several biomolecule probe regions, as well as a graphical code to identify the embedded probes. Using high-speed imaging, we have developed and optimized a flow-through system that (1) allows for a high particle throughput, (2) ensures proper particle alignment for decoding and target quantification, and (3) can be reliably operated continuously without clogging. A tapered channel flanked by side focusing streams is used to orient the flexible, tablet-shaped particles into a well-ordered flow in the center of the channel. The effects of channel geometry, particle geometry, particle composition, particle loading density, and barcode design are explored to determine the best combination for eventual use in biological assays. Particles in the optimized system move at velocities of approximately 50 cm s(-1) and with throughputs of approximately 40 particles s(-1). Simple physical models and CFD simulations have been used to investigate flow behavior in the device.

[1]  Larry Gold,et al.  Proteomics and diagnostics: Let's Get Specific, again. , 2008, Current opinion in chemical biology.

[2]  T. Golub,et al.  A method for high-throughput gene expression signature analysis , 2006, Genome Biology.

[3]  Yasutaka Morita,et al.  Micromachining microcarrier-based biomolecular encoding for miniaturized and multiplexed immunoassay. , 2003, Analytical chemistry.

[4]  R. Misra,et al.  Biomaterials , 2008 .

[5]  C. Bowman,et al.  Mechanical properties of hydrogels and their experimental determination. , 1996, Biomaterials.

[6]  P. Crosland-Taylor A Device for Counting Small Particles suspended in a Fluid through a Tube , 1953, Nature.

[7]  A. Agadir,et al.  Cytometric bead array: a multiplexed assay platform with applications in various areas of biology. , 2004, Clinical immunology.

[8]  Kathryn L Kellar,et al.  Multiplexed microsphere-based flow cytometric immunoassays for human cytokines. , 2003, Journal of immunological methods.

[9]  David G Spiller,et al.  Encoded microcarriers for high-throughput multiplexed detection. , 2006, Angewandte Chemie.

[10]  Ruey-Jen Yang,et al.  Three-dimensional hydrodynamic focusing in two-layer polydimethylsiloxane (PDMS) microchannels , 2007 .

[11]  D. Vignali Multiplexed particle-based flow cytometric assays. , 2000, Journal of immunological methods.

[12]  W. Kalow,et al.  Pharmacogenetics and pharmacogenomics: origin, status, and the hope for personalized medicine , 2006, The Pharmacogenomics Journal.

[13]  Kathryn L Kellar,et al.  Multiplexed microsphere-based flow cytometric assays. , 2002, Experimental hematology.

[14]  Alex Groisman,et al.  High-throughput and high-resolution flow cytometry in molded microfluidic devices. , 2006, Analytical chemistry.

[15]  R. Grimshaw Journal of Fluid Mechanics , 1956, Nature.

[16]  C. Sewter,et al.  An encoded particle array tool for multiplex bioassays. , 2003, Assay and drug development technologies.

[17]  Dhananjay Dendukuri,et al.  Stop-flow lithography in a microfluidic device. , 2007, Lab on a chip.

[18]  R. Rosenfeld Nature , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[19]  T. Secomb,et al.  Viscous motion of disk-shaped particles through parallel-sided channels with near-minimal widths , 1991, Journal of Fluid Mechanics.

[20]  Timothy W. Secomb,et al.  The squeezing of red blood cells through parallel-sided channels with near-minimal widths , 1992, Journal of Fluid Mechanics.

[21]  Radoje Drmanac,et al.  Multiplexed SNP genotyping using nanobarcode particle technology , 2006, Analytical and bioanalytical chemistry.

[22]  Hee Chan Kim,et al.  Recent advances in miniaturized microfluidic flow cytometry for clinical use , 2007, Electrophoresis.

[23]  R. G. Freeman,et al.  Submicrometer metallic barcodes. , 2001, Science.

[24]  Wen-Hsin Hsieh,et al.  Hydrodynamic focusing investigation in a micro-flow cytometer , 2007, Biomedical microdevices.

[25]  R Skalak,et al.  A two-dimensional model for capillary flow of an asymmetric cell. , 1982, Microvascular research.

[26]  W. Deen Analysis Of Transport Phenomena , 1998 .

[27]  Parag A. Pathak,et al.  Massachusetts Institute of Technology , 1964, Nature.

[28]  大房 健 基礎講座 電気泳動(Electrophoresis) , 2005 .

[29]  S. P. Fodor,et al.  Multiplexed biochemical assays with biological chips , 1993, Nature.

[30]  Dong-Chul Han,et al.  Plastic microchip flow cytometer based on 2- and 3-dimensional hydrodynamic flow focusing , 2003 .

[31]  Mehmet Toner,et al.  Multifunctional Encoded Particles for High-Throughput Biomolecule Analysis , 2007, Science.

[32]  S. Takayama,et al.  Microfluidics for flow cytometric analysis of cells and particles , 2005, Physiological measurement.

[33]  A. Turygin,et al.  Gel-Based Microchips: History and Prospects , 2004, Molecular Biology.

[34]  R J Fulton,et al.  Advanced multiplexed analysis with the FlowMetrix system. , 1997, Clinical chemistry.

[35]  J. M. Fitz-Gerald,et al.  Mechanics of red-cell motion through very narrow capillaries , 1969, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[36]  H. Stone,et al.  Geometrical focusing of cells in a microfluidic device: an approach to separate blood plasma. , 2006, Biorheology.