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Enhanced Signals and Fast Nucleic Acid Hybridization By Microfluidic Chaotic Mixing

✍ Scribed by Jian Liu; Brian A. Williams; Richele M. Gwirtz; Barbara J. Wold; Stephen Quake


Book ID
102727407
Publisher
John Wiley and Sons
Year
2006
Tongue
English
Weight
803 KB
Volume
45
Category
Article
ISSN
0044-8249

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✦ Synopsis


Nucleic acid hybridization techniques are widely used in both fundamental and clinical research to identify genes and mutants, to map their correlations, and to analyze their expression. DNA microarrays immobilize thousands of oligonucleotides, cDNA (c = complementary) clones, or polymerase-chain-reaction (PCR) products on the solid substrate, thus providing a powerful tool for the large-scale detection of target genes. [1,2] However, hybridization in conventional microarray experiments is performed in a diffusion-limited manner, which is quite inefficient. The hybridization process may take 8-24 h, during which period the characteristic distance (1-3 mm) that a target DNA molecule can diffuse is still one order of magnitude less than the typical size of most microarrays (> 10 mm). [3,4] Herein we describe an effective answer to that problem using microfluidic chaotic mixing. Our polydimethylsilicane (PDMS) devices use integrated peristaltic pumps to circulate the solution between two large chambers, while chaotically mixing the components of the solution in bridge channels at the same time. We demonstrate that this approach dramatically enhances hybridization signals and improves sensitivity by nearly one order of magnitude relative to the conventional static-hybridization method over the same length of time. Alternatively, for a desired sensitivity, dynamic mixing can be used to accelerate the hybridization process by a factor of three or more. This approach offers many benefits, including high sensitivity, rapid results, better reproducibility, low cost, compatibility with commercial microarray slides, and ease of large-scale integration.


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