4.2 Article

SIZE-CONTROLLED DROPLET GENERATION IN A MICROFLUIDIC DEVICE FOR RARE DNA AMPLIFICATION BY OPTIMIZING ITS EFFECTIVE PARAMETERS

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WORLD SCIENTIFIC PUBL CO PTE LTD
DOI: 10.1142/S0219519418500021

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Droplet generation; droplet PCR; generalized linear model; microfluidic flow-focusing device; optimization

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Versatility and portability of microfluidic devices play a dominant role in their widespread use by researchers. Droplet-based microfluidic devices have been extensively used due to their precise control over sample volume, and ease of manipulating and addressing each droplet on demand. Droplet-based polymerase chain reaction (PCR) devices are particularly desirable in single DNA amplification. If the droplets are small enough to contain only one DNA molecule, single molecule amplification becomes possible, which can be advantageous in several cases such as early cancer detection. In this work, flow-focusing microfluidic droplet generation's parameters are numerically investigated and optimized for generating the smallest droplet possible, while considering fabrication limits. Taguchi design of experiment method is used to study the effects of key parameters in droplet generation. By exploiting this approach, a droplet with a radius of 111 nm is generated using a 3 mu m orifice. Since the governing physics of the droplet generation process is not totally understood yet, by means of analysis of variance (ANOVA) analysis, a generalized linear model (GLM) is proposed to predict the droplet radius, given the values of eight major parameters affecting the droplet size. The proposed model shows a correlation of 95.3% and 64.95% for droplets of radius greater than and lower than 5 mu m, respectively. Finally, the source of this variation of behavior in different size scales is identified.

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