Design of Continuous-Flow Lab-on-Chip with 3D Microfluidic Network for Sample Preparation

Microfluidic labs-on-chip have fueled the automation of biochemical protocols (assays) on a tiny device and found versatile applications to DNA analysis, medical diagnostics, forensics, and drug design. Sample preparation, which includes dilution of fluids or solution mixing, is needed as a preprocessing step for most of the assays. Although continuous-flow microfluidic biochips (CFMB) are being widely used by chemists and biologists, accurate sample preparation with them is a challenge and the technology lacks an automated CAD-tool that can be deployed to design the underlying fluidic network. In this paper, we present, the physical design of a 3D-fluidic network that can be used as a universal platform for dilution preparation. The network does not need any control-valve for fluid navigation or multiplexing, yet it is fully programmable. A sample with any given concentration factor (CF) can be produced as output-flow by controlling only the rate of input-fluid injection. Simulation with COMSOL Multiphysics Software shows that the proposed free-flowing CFMB outperforms prior approaches in achieving the accuracy of CFs and diversity of applications.

[1]  B. Olson,et al.  Comparison of two- and three-dimensional simulations of miscible Richtmyer-Meshkov instability with multimode initial conditions , 2014 .

[2]  John Crank,et al.  The Mathematics Of Diffusion , 1956 .

[3]  Bhargab B. Bhattacharya,et al.  COMSOL-Based Design and Validation of Dilution Algorithm with Continuous-Flow Lab-on-Chip , 2017 .

[4]  Benjamin Schuler,et al.  Microfluidic mixers for the investigation of rapid protein folding kinetics using synchrotron radiation circular dichroism spectroscopy. , 2008, Analytical chemistry.

[5]  Robin H. Liu,et al.  Passive mixing in a three-dimensional serpentine microchannel , 2000, Journal of Microelectromechanical Systems.

[6]  Jeffrey M. Perkel,et al.  Microfluidics—Bringing New Things to Life Science , 2008 .

[7]  Hengzi Wang,et al.  Numerical investigation of mixing in microchannels with patterned grooves , 2003 .

[8]  Jessica Melin,et al.  Microfluidic large-scale integration: the evolution of design rules for biological automation. , 2007, Annual review of biophysics and biomolecular structure.

[9]  Ulf Schlichtmann,et al.  Testing microfluidic Fully Programmable Valve Arrays (FPVAs) , 2017, Design, Automation & Test in Europe Conference & Exhibition (DATE), 2017.

[10]  Roman Stocker,et al.  Bacterial chemotaxis in linear and nonlinear steady microfluidic gradients. , 2010, Nano letters.

[11]  Kai Hu,et al.  Control-Layer Routing and Control-Pin Minimization for Flow-Based Microfluidic Biochips , 2017, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.

[12]  Sebastian J Maerkl,et al.  A software-programmable microfluidic device for automated biology. , 2011, Lab on a chip.

[13]  Laurie E Locascio,et al.  A robust diffusion-based gradient generator for dynamic cell assays. , 2012, Lab on a chip.

[14]  G. Whitesides,et al.  Generation of Solution and Surface Gradients Using Microfluidic Systems , 2000 .

[15]  Chia-Hung Liu,et al.  Reactant minimization during sample preparation on digital microfluidic biochips using skewed mixing trees , 2012, 2012 IEEE/ACM International Conference on Computer-Aided Design (ICCAD).

[16]  Philip Brisk,et al.  Random design of microfluidics. , 2016, Lab on a chip.

[17]  Wei Duan,et al.  Lab-on-a-chip: a component view , 2010 .

[18]  P. K. Patowari,et al.  Computational Analysis for Mixing of Fluids Flowing through Micro- Channels of Different Geometries , 2014 .

[19]  Mohammad A. Qasaimeh,et al.  Microfluidic quadrupole and floating concentration gradient , 2011, Nature communications.

[20]  Tsung-Yi Ho,et al.  A top-down synthesis methodology for flow-based microfluidic biochips considering valve-switching minimization , 2013, ISPD '13.

[21]  Howard A. Stone,et al.  Introduction to Fluid Dynamics for Microfluidic Flows , 2007 .

[22]  Samuel K Sia,et al.  Commercialization of microfluidic point-of-care diagnostic devices. , 2012, Lab on a chip.

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

[24]  Kai Hu,et al.  Fault Diagnosis for Leakage and Blockage Defects in Flow-Based Microfluidic Biochips , 2016, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.

[25]  Thomas J Ober,et al.  Active mixing of complex fluids at the microscale , 2015, Proceedings of the National Academy of Sciences.

[26]  Raymond H. W. Lam,et al.  Dynamics of Microvalve Operations in Integrated Microfluidics , 2014, Micromachines.

[27]  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.

[28]  Sudip Roy,et al.  Dilution and Mixing Algorithms for Flow-Based Microfluidic Biochips , 2017, IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems.