Overview

We have been developing a microfluidic platform for secure, high-throughput de novo solid-phase DNA oligonucletoide synthesis through multidisciplinary and academic-industry collaborations (Prof. Philip Brisk, UCR; Prof. William Grover, UCR; Prof. Mohammed Al Faruque, UCI; PharmaSeq, Inc.). Solid-phase synthesis of DNA has extensive synthetic biology applications including development of libraries of gene constructs to engineer new functions and elucidate genetic mechanisms. More recently, synthetic DNA has also been explored as a medium for digital data storage. A novel redesign of the DNA manufacturing process is required to improve the throughput, error rates, and cost of production of industry-standard microarray technologies.

The enabling technology which we employ is the p-Chip, a microtransponder developed by project partner, PharmaSeq, Inc., which acts as the solid-phase support for oligonucleotide synthesis and transmits a unique identifier via radio-frequency signals upon laser illumination. A microfluidic manifold is utilized to rapidly sort p-Chips, in real-time, to reservoirs which apply the appropriate DNA chemistry to synthesize and append the next oligonucleotide in the desired sequence. To identify an optimized design for the microfludic p-Chip sorter, we are modeling the motion of p-Chips in microchannel fluid flow using computational fluid dynamics (CFD) simulations that account for fluid-particle and particle-particle interactions. The CFD models will be validated through experimental observations of particle behavior and trajectories. Towards our aim for a secure, high-throughput platform for DNA synthesis, we will design and implement algorithms to allow for real-time control and prediction of sorting actuations and integrate methods to improve the robustness of the sorter system to side-channel attacks. 

Related Publications

Mandecki W, Ardelt B, Coradetti T, Davidowitz H, Flint J, Huang Z, Kopacka W, Lin X, Wang Z, Darzynkiewicz Z (2006) Microtransponders, the miniature RFID electronic chips, as platforms for cell growth in cytotoxicity assays, Cytometry Part A, 69A:1097-1105. 

Wang J, Rodgers VGJ, Brisk P, Grover WH (2017) MOPSA: A microfluidics-optimized particle simulation algorithm, Biomicrofluidics 11, 034121. 

Kahkeshani S, Haddidi H, Di Carlo D (2016) Preferred interparticle spacings in trains of particles in inertial microchannel flows, Journal of Fluid Mechanics, 786.