Microfluidic Chips for Life Sciences-A Comparison of Low Entry Manufacturing Technologies.

Microfluidic water-in-oil droplets are a versatile tool for biological and biochemical applications due to the advantages of extremely small monodisperse reaction vessels in the pL-nL range. A key factor for the successful dissemination of this technology to life science laboratory users is the ability to produce microfluidic droplet generators and related accessories by low-entry barrier methods, which enable rapid prototyping and manufacturing of devices with low instrument and material costs. The direct, experimental side-by-side comparison of three commonly used additive manufacturing (AM) methods, namely fused deposition modeling (FDM), inkjet printing (InkJ), and stereolithography (SLA), is reported. As a benchmark, micromilling (MM) is used as an established method. To demonstrate which of these methods can be easily applied by the non-expert to realize applications in topical fields of biochemistry and microbiology, the methods are evaluated with regard to their limits for the minimum structure resolution in all three spatial directions. The suitability of functional SLA and MM chips to replace classic SU-8 prototypes is demonstrated on the basis of representative application cases.

[1]  Rafał Walczak,et al.  Inkjet 3D printing of microfluidic structures—on the selection of the printer towards printing your own microfluidic chips , 2015 .

[2]  Roland Zengerle,et al.  Digital droplet PCR on disk. , 2016, Lab on a chip.

[3]  G. Stephanopoulos,et al.  Microfluidic high-throughput culturing of single cells for selection based on extracellular metabolite production or consumption , 2014, Nature Biotechnology.

[4]  Bill W Colston,et al.  High-throughput quantitative polymerase chain reaction in picoliter droplets. , 2008, Analytical chemistry.

[5]  Philip J. Kitson,et al.  Configurable 3D-Printed millifluidic and microfluidic 'lab on a chip' reactionware devices. , 2012, Lab on a chip.

[6]  Piotr Garstecki,et al.  Droplet microfluidics for microbiology: techniques, applications and challenges. , 2016, Lab on a chip.

[7]  Martin Fischlechner,et al.  Ultrahigh-throughput–directed enzyme evolution by absorbance-activated droplet sorting (AADS) , 2016, Proceedings of the National Academy of Sciences.

[8]  M. Breadmore,et al.  Using Printing Orientation for Tuning Fluidic Behavior in Microfluidic Chips Made by Fused Deposition Modeling 3D Printing. , 2017, Analytical chemistry.

[9]  James C. Hu,et al.  Gene expression from plasmids containing the araBAD promoter at subsaturating inducer concentrations represents mixed populations. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Andrew J deMello,et al.  A 3D-printed microcapillary assembly for facile double emulsion generation. , 2014, Lab on a chip.

[11]  Xingyu Jiang,et al.  Why microfluidics? Merits and trends in chemical synthesis. , 2017, Lab on a chip.

[12]  Kirsten Jung,et al.  Timing and dynamics of single cell gene expression in the arabinose utilization system. , 2008, Biophysical journal.

[13]  Niall P Macdonald,et al.  Multimaterial 3D Printed Fluidic Device for Measuring Pharmaceuticals in Biological Fluids. , 2018, Analytical chemistry.

[14]  J. Nielsen,et al.  High-throughput screening for industrial enzyme production hosts by droplet microfluidics. , 2014, Lab on a chip.

[15]  Phil Stephens,et al.  Simple and Versatile 3D Printed Microfluidics Using Fused Filament Fabrication , 2016, PloS one.

[16]  J. Brennan,et al.  Coupled enzyme reaction microarrays based on pin-printing of sol–gel derived biomaterials , 2003 .

[17]  Daniel Filippini,et al.  PDMS lab-on-a-chip fabrication using 3D printed templates. , 2014, Lab on a chip.

[18]  Jia Ming Zhang,et al.  Droplet generation in cross-flow for cost-effective 3D-printed “plug-and-play” microfluidic devices , 2016 .

[19]  G. Whitesides,et al.  Poly(dimethylsiloxane) as a material for fabricating microfluidic devices. , 2002, Accounts of chemical research.

[20]  J. Voldman,et al.  Designable 3D Microshapes Fabricated at the Intersection of Structured Flow and Optical Fields. , 2018, Small.

[21]  Klaus-Peter Zauner,et al.  Interdroplet bilayer arrays in millifluidic droplet traps from 3D-printed moulds. , 2014, Lab on a chip.

[22]  Andrew D Griffiths,et al.  Enhanced chemical synthesis at soft interfaces: a universal reaction-adsorption mechanism in microcompartments. , 2014, Physical review letters.

[23]  Wingki Lee,et al.  Role of geometry and fluid properties in droplet and thread formation processes in planar flow focusing , 2009 .

[24]  H. S. Rho,et al.  Mapping of Enzyme Kinetics on a Microfluidic Device , 2016, PloS one.

[25]  Christoph A. Merten,et al.  Drop-based microfluidic devices for encapsulation of single cells. , 2008, Lab on a chip.

[26]  D. Weitz,et al.  Fluorescence-activated droplet sorting (FADS): efficient microfluidic cell sorting based on enzymatic activity. , 2009, Lab on a chip.

[27]  Christoph A. Merten,et al.  Droplet-based microfluidic platforms for the encapsulation and screening of Mammalian cells and multicellular organisms. , 2008, Chemistry & biology.

[28]  Petr Smejkal,et al.  Comparing Microfluidic Performance of Three-Dimensional (3D) Printing Platforms. , 2017, Analytical chemistry.

[29]  A. Woolley,et al.  Custom 3D printer and resin for 18 μm × 20 μm microfluidic flow channels. , 2017, Lab on a chip.

[30]  Michael J. Beauchamp,et al.  Optical Approach to Resin Formulation for 3D Printed Microfluidics. , 2015, RSC advances.

[31]  M. Hashimoto,et al.  3D printed fittings and fluidic modules for customizable droplet generators , 2019, RSC advances.

[32]  L. Mazutis,et al.  Quantitative and sensitive detection of rare mutations using droplet-based microfluidics. , 2011, Lab on a chip.

[33]  Michael J. Beauchamp,et al.  3D Printed Microfluidic Features Using Dose Control in X, Y, and Z Dimensions , 2018, Micromachines.

[34]  Markus Reischl,et al.  Information Fusion of Image Analysis, Video Object Tracking, and Data Mining of Biological Images using the Open Source MATLAB Toolbox Gait-CAD , 2012 .

[35]  M. Bowser,et al.  3D Printed Micro Free-Flow Electrophoresis Device. , 2016, Analytical chemistry.

[36]  Benjamin Richter,et al.  3D Laser Micro- and Nanoprinting: Challenges for Chemistry. , 2017, Angewandte Chemie.

[37]  Andrew D Griffiths,et al.  Droplet-based microfluidic high-throughput screening of heterologous enzymes secreted by the yeast Yarrowia lipolytica , 2017, Microbial Cell Factories.

[38]  Hongyuan Jiang,et al.  Sequential Coalescence Enabled Two-Step Microreactions in Triple-Core Double-Emulsion Droplets Triggered by an Electric Field. , 2017, Small.

[39]  L. Mazutis,et al.  DNA Nanoparticles for Improved Protein Synthesis In Vitro , 2016, Angewandte Chemie.

[40]  Leroy Cronin,et al.  Customizable 3D Printed ‘Plug and Play’ Millifluidic Devices for Programmable Fluidics , 2015, PloS one.

[41]  David A. Rolfe,et al.  Comparison of Microscale Rapid Prototyping Techniques , 2014 .

[42]  J. Thiele,et al.  Optimizing Process Parameters in Commercial Micro‐Stereolithography for Forming Emulsions and Polymer Microparticles in Nonplanar Microfluidic Devices , 2018, Advanced Materials Technologies.

[43]  R. Ramanujan,et al.  Magnetic Janus particles synthesized using droplet micro-magnetofluidic techniques for protein detection. , 2017, Lab on a chip.

[44]  Andres A. Aguirre-Pablo,et al.  A simple and low-cost fully 3D-printed non-planar emulsion generator , 2016 .

[45]  F. Hollfelder,et al.  Ultrahigh-throughput discovery of promiscuous enzymes by picodroplet functional metagenomics , 2015, Nature Communications.

[46]  Bastian E. Rapp,et al.  Let there be chip—towards rapid prototyping of microfluidic devices: one-step manufacturing processes , 2011 .

[47]  Rustem F Ismagilov,et al.  Multi-step synthesis of nanoparticles performed on millisecond time scale in a microfluidic droplet-based system. , 2004, Lab on a chip.

[48]  S. Quake,et al.  Microfluidics: Fluid physics at the nanoliter scale , 2005 .

[49]  D. Baker,et al.  Emergence of a catalytic tetrad during evolution of a highly active artificial aldolase , 2016, Nature Chemistry.

[50]  Sidra Waheed,et al.  3D printed microfluidic devices: enablers and barriers. , 2016, Lab on a chip.

[51]  Chee Meng Benjamin Ho,et al.  3D printed microfluidics for biological applications. , 2015, Lab on a chip.

[52]  Ina G Siller,et al.  3D Printed Microfluidic Mixers-A Comparative Study on Mixing Unit Performances. , 2018, Small.

[53]  M. Breadmore,et al.  One-Step Fabrication of a Microfluidic Device with an Integrated Membrane and Embedded Reagents by Multimaterial 3D Printing. , 2017, Analytical chemistry.

[54]  Lucia L. Prieto-Godino,et al.  Open Labware: 3-D Printing Your Own Lab Equipment , 2015, PLoS biology.

[55]  Gábor Harsányi,et al.  Characterization of rapid PDMS casting technique utilizing molding forms fabricated by 3D rapid prototyping technology (RPT) , 2014 .

[56]  D. G. Gibson,et al.  Enzymatic assembly of DNA molecules up to several hundred kilobases , 2009, Nature Methods.

[57]  Elisabeth Verpoorte,et al.  Fused Deposition Modeling 3D Printing for (Bio)analytical Device Fabrication: Procedures, Materials, and Applications , 2017, Analytical chemistry.

[58]  Aliaa I. Shallan,et al.  Cost-effective three-dimensional printing of visibly transparent microchips within minutes. , 2014, Analytical chemistry.