3D printing: an emerging tool for novel microfluidics and lab-on-a-chip applications

In the past few years, 3D printing technology has witnessed an explosive growth, penetrating various aspects of our lives. Current best-in-class 3D printers can fabricate micrometer scale objects, which has made fabrication of microfluidic devices possible. The highest achievable resolution is already at nanometer scale, which is continuing to drop. Since geometric complexity is not a concern for 3D printing, novel 3D microfluidics and lab-on-a-chip systems that are otherwise impossible to produce with traditional 2D microfabrication technology have started to emerge in recent years. In this review, we first introduce the basics of 3D printing technology for the microfluidic community and then summarize its emerging applications in creating novel microfluidic devices. We foresee widespread utilization of 3D printing for future developments in microfluidic engineering and lab-on-a-chip technology.

[1]  Jaephil Do,et al.  A polymer lab-on-a-chip for magnetic immunoassay with on-chip sampling and detection capabilities. , 2008, Lab on a chip.

[2]  S. Lockwood,et al.  A 3D printed fluidic device that enables integrated features. , 2013, Analytical chemistry.

[3]  Leong Kah Fai,et al.  Rapid Prototyping: Principles and Applications in Manufacturing , 2003 .

[4]  Yasunori Saotome,et al.  Superplastic backward microextrusion of microparts for micro-electro-mechanical systems , 2001 .

[5]  M. Heckele,et al.  Review on micro molding of thermoplastic polymers , 2004 .

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

[7]  Amy Rachel Betz,et al.  Microfluidic formation of monodispersed spherical microgels composed of triple‐network crosslinking , 2011 .

[8]  G. Whitesides,et al.  Soft lithographic methods for nano-fabrication , 1997 .

[9]  Kornel Ehmann,et al.  Laser-induced plasma in aqueous media: numerical simulation and experimental validation of spatial and temporal profiles. , 2014, Applied optics.

[10]  Seung Ki Moon,et al.  Application of 3D printing technology for designing light-weight unmanned aerial vehicle wing structures , 2014, International Journal of Precision Engineering and Manufacturing-Green Technology.

[11]  M. Padgett,et al.  Development of a 3D printer using scanning projection stereolithography , 2015, Scientific Reports.

[12]  Jun Wang,et al.  One-step microfabrication of fused silica by laser ablation of an organic solution , 1999 .

[13]  Jong Wook Hong,et al.  Integrated nanoliter systems , 2003, Nature Biotechnology.

[14]  V. Piotter,et al.  Various replication techniques for manufacturing three-dimensional metal microstructures , 1997 .

[15]  G. Whitesides,et al.  Soft Lithography. , 1998, Angewandte Chemie.

[16]  A. Manz,et al.  Lab-on-a-chip: microfluidics in drug discovery , 2006, Nature Reviews Drug Discovery.

[17]  Xiao Li,et al.  Fabrication of three-dimensional microfluidic channels in a single layer of cellulose paper , 2014, Microfluidics and Nanofluidics.

[18]  Yih‐Lin Cheng,et al.  Development of dynamic masking rapid prototyping system for application in tissue engineering , 2009 .

[19]  Jie Xu,et al.  Deformability-based circulating tumor cell separation with conical-shaped microfilters: Concept, optimization, and design criteria. , 2015, Biomicrofluidics.

[20]  Albert Folch,et al.  Mail-order microfluidics: evaluation of stereolithography for the production of microfluidic devices. , 2014, Lab on a chip.

[21]  Seok-Hee Lee,et al.  Dithering method for improving the surface quality of a microstructure in projection microstereolithography , 2011 .

[22]  Yayue Pan,et al.  A Novel Projection based Electro-Stereolithography ( PES ) Process for Composite Printing , 2015 .

[23]  Adam T Woolley,et al.  Single-monomer formulation of polymerized polyethylene glycol diacrylate as a nonadsorptive material for microfluidics. , 2011, Analytical chemistry.

[24]  Seok-Hee Lee,et al.  Design of microstereolithography system based on dynamic image projection for fabrication of three-dimensional microstructures , 2006 .

[25]  Jerry Y. H. Fuh,et al.  Selective Laser Sintering , 2001 .

[26]  Jian Cao,et al.  Unidirectional magnetic field assisted Laser Induced Plasma Micro-Machining , 2015 .

[27]  Howon Lee,et al.  Ultralight, ultrastiff mechanical metamaterials , 2014, Science.

[28]  Steven J. Keating,et al.  Beyond 3D Printing: The New Dimensions of Additive Fabrication , 2014 .

[29]  Koji Ikuta,et al.  Development of mass productive micro stereo lithography (Mass-IH process) , 1996, Proceedings of Ninth International Workshop on Micro Electromechanical Systems.

[30]  Ming Lei,et al.  Hard and soft micromachining for BioMEMS: review of techniques and examples of applications in microfluidics and drug delivery. , 2004, Advanced drug delivery reviews.

[31]  D. Drikakis,et al.  Multiscale methods for micro/nano flows and materials , 2008 .

[32]  Xuan Song,et al.  Development of a Low-Cost Parallel Kinematic Machine for Multidirectional Additive Manufacturing , 2015 .

[33]  J. Samitier,et al.  Bioprinting of 3D hydrogels. , 2015, Lab on a chip.

[34]  G. Whitesides,et al.  Applications of microfluidics in chemical biology. , 2006, Current opinion in chemical biology.

[35]  A. Miyawaki,et al.  Nano-aquarium for dynamic observation of living cells fabricated by femtosecond laser direct writing of photostructurable glass , 2008, Biomedical microdevices.

[36]  A. Woolley,et al.  3D printed microfluidic devices with integrated valves. , 2015, Biomicrofluidics.

[37]  Chi Zhou,et al.  Development of a Multi-material Mask-Image-Projection-based Stereolithography for the Fabrication of Digital Materials , 2011 .

[38]  Hongkai Wu,et al.  Direct, one-step molding of 3D-printed structures for convenient fabrication of truly 3D PDMS microfluidic chips , 2015 .

[39]  Frank W. Liou,et al.  Direct Three-Dimensional Layer Metal Deposition , 2010 .

[40]  Sergio Pellegrino,et al.  Design of lightweight structural components for direct digital manufacturing , 2012 .

[41]  Neil Hopkinson,et al.  Rapid manufacturing : an industrial revolution for the digital age , 2006 .

[42]  C. K. Chua,et al.  Dual Material Rapid Prototyping Techniques for the Development of Biomedical Devices. Part 1: Space Creation , 2001 .

[43]  Murat Okandan,et al.  Development of surface micromachining technologies for microfluidics and bioMEMS , 2001, MOEMS-MEMS.

[44]  Paulo Jorge Da Silva bartolo,et al.  Metal filled resin for stereolithography metal part , 2008 .

[45]  J. Muth,et al.  3D Printing of Free Standing Liquid Metal Microstructures , 2013, Advanced materials.

[46]  Yong Chen,et al.  A Fast Mask Projection Stereolithography Process for Fabricating Digital Models in Minutes , 2012 .

[47]  Chee Kai Chua,et al.  Dual Material Rapid Prototyping Techniques for the Development of Biomedical Devices. Part 2: Secondary Powder Deposition , 2002 .

[48]  G. Karniadakis,et al.  Microflows and Nanoflows: Fundamentals and Simulation , 2001 .

[49]  Jie Xu,et al.  The effects of 3D channel geometry on CTC passing pressure--towards deformability-based cancer cell separation. , 2014, Lab on a chip.

[50]  Joohyun Choi,et al.  Analysis of laser control effects for direct metal deposition process , 2006 .

[51]  Krisna C. Bhargava,et al.  Discrete elements for 3D microfluidics , 2014, Proceedings of the National Academy of Sciences.

[52]  Francis H. Zenie,et al.  Accelerating Drug Discovery , 1994, Bio/Technology.

[53]  Hang Ye,et al.  A Novel Low-Cost Stereolithography Process Based on Vector Scanning and Mask Projection for High-Accuracy, High-Speed, High-Throughput, and Large-Area Fabrication , 2015, J. Comput. Inf. Sci. Eng..

[54]  A. Folch Introduction to BioMEMS , 2012 .

[55]  G. K. Lewis,et al.  Directed light fabrication of a solid metal hemisphere using 5-axis powder deposition , 1998 .

[56]  G. Whitesides,et al.  Soft lithography in biology and biochemistry. , 2001, Annual review of biomedical engineering.

[57]  Ventola Cl Medical Applications for 3D Printing: Current and Projected Uses. , 2014 .

[58]  Xibing Gong,et al.  Review on powder-based electron beam additive manufacturing technology , 2012 .

[59]  Barry Berman,et al.  3D printing: the new industrial revolution , 2012, IEEE Engineering Management Review.

[60]  Ryan R. Anderson,et al.  Microfluidic Valves Made From Polymerized Polyethylene Glycol Diacrylate. , 2014, Sensors and actuators. B, Chemical.

[61]  Philip H. King Towards rapid 3D direct manufacture of biomechanical microstructures , 2009 .

[62]  Dejun Jing,et al.  Experimental and Numerical Study on the Flow of Fine Powders from Small-Scale Hoppers Applied to SLS Multi-Material Deposition-Part I , 2002 .

[63]  G. Klein,et al.  3D printing and neurosurgery--ready for prime time? , 2013, World neurosurgery.

[64]  Kaufui Wong,et al.  A Review of Additive Manufacturing , 2012 .

[65]  Jean-Pierre Kruth,et al.  Composites by rapid prototyping technology , 2010 .

[66]  Robin A Felder,et al.  3D cell culture opens new dimensions in cell-based assays. , 2009, Drug discovery today.

[67]  J. Lewis,et al.  3D Printing of Interdigitated Li‐Ion Microbattery Architectures , 2013, Advanced materials.

[68]  Dong-Yol Yang,et al.  Fabrication of a bunch of sub-30-nm nanofibers inside microchannels using photopolymerization via a long exposure technique , 2006 .

[69]  A. Liou,et al.  Injection molding of polymer micro- and sub-micron structures with high-aspect ratios , 2006 .

[70]  Nam Soo Kim,et al.  Thermo-mechanical Characterization of Metal/Polymer Composite Filaments and Printing Parameter Study for Fused Deposition Modeling in the 3D Printing Process , 2015, Journal of Electronic Materials.

[71]  G J Suaning,et al.  Fabrication of implantable microelectrode arrays by laser cutting of silicone rubber and platinum foil , 2005, Journal of neural engineering.

[72]  Wei Sun,et al.  Multi‐nozzle deposition for construction of 3D biopolymer tissue scaffolds , 2005 .

[73]  J. Ross,et al.  The shape of things to come: 3D printing in medicine. , 2014, JAMA.

[74]  Joseph J. Beaman,et al.  Discrete Multi-Material Selective Laser Sintering (M 2 SLS): Development for an Application in Complex Sand Casting Core Arrays , 2000 .

[75]  Kornel Ehmann,et al.  High-speed fabrication of microchannels using line-based laser induced plasma micromachining , 2015 .

[76]  Mohammad Hassan Saidi,et al.  Rheology effects on cross-stream diffusion in a Y-shaped micromixer , 2014 .

[77]  Steven W Pryor,et al.  Implementing a 3D Printing Service in an Academic Library , 2014 .

[78]  Sushanta K. Mitra,et al.  Microfluidics and Nanofluidics Handbook : Fabrication, Implementation, and Applications , 2011 .

[79]  Gabriele Wurm,et al.  Prospective study on cranioplasty with individual carbon fiber reinforced polymer (CFRP) implants produced by means of stereolithography. , 2004, Surgical neurology.

[80]  Wei Xue,et al.  Towards a Dynamic Clamp for Neurochemical Modalities , 2013, BMC Neuroscience.

[81]  K. Lee,et al.  Two‐photon stereolithography for realizing ultraprecise three‐dimensional nano/microdevices , 2009 .

[82]  Sangeeta N Bhatia,et al.  Three-dimensional tissue fabrication. , 2004, Advanced drug delivery reviews.

[83]  Jiang Zhe,et al.  Continuous 3D particle focusing in a microchannel with curved and symmetric sharp corner structures , 2015 .

[84]  P. Renaud,et al.  Combining microstereolithography and thick resist UV lithography for 3D microfabrication , 1998, Proceedings MEMS 98. IEEE. Eleventh Annual International Workshop on Micro Electro Mechanical Systems. An Investigation of Micro Structures, Sensors, Actuators, Machines and Systems (Cat. No.98CH36176.

[85]  Wales Fast, Precise, Safe Prototypes with FDM , 1991 .

[86]  Yong Chen,et al.  A layerless additive manufacturing process based on CNC accumulation , 2011 .

[87]  Albert Folch,et al.  3D-printed microfluidic automation. , 2015, Lab on a chip.

[88]  K. Pister,et al.  Surface micromachined polysilicon heart cell force transducer , 2000, Journal of Microelectromechanical Systems.

[89]  ニール ガーシェンフェルド,et al.  How to Make Almost Anything : The Digital Fabrication Revolution , 2012 .

[90]  S. Quake,et al.  Microfluidic Large-Scale Integration , 2002, Science.

[91]  T. Huang,et al.  Accelerating drug discovery via organs-on-chips. , 2013, Lab on a chip.

[92]  David L. Bourell,et al.  Sustainability issues in laser-based additive manufacturing , 2010 .

[93]  Sushanta K. Mitra,et al.  Microfluidics and Nanofluidics Handbook, Two Volume Set , 2011 .

[94]  D. Beebe,et al.  Physics and applications of microfluidics in biology. , 2002, Annual review of biomedical engineering.

[95]  Jeff Punch,et al.  A comparison between the hydrodynamic characteristics of 3D-printed polymer and etched silicon microchannels , 2015 .

[96]  L. Murr,et al.  Metal Fabrication by Additive Manufacturing Using Laser and Electron Beam Melting Technologies , 2012 .

[97]  Chi Zhou,et al.  Digital material fabrication using mask‐image‐projection‐based stereolithography , 2013 .

[98]  D. Diamond,et al.  Advances in three-dimensional rapid prototyping of microfluidic devices for biological applications. , 2014, Biomicrofluidics.

[99]  Gábor Harsányi,et al.  3D Rapid Prototyping Technology (RPT) as a powerful tool in microfluidic development , 2010 .

[100]  F. Tseng,et al.  EFAB: rapid, low-cost desktop micromachining of high aspect ratio true 3-D MEMS , 1999, Technical Digest. IEEE International MEMS 99 Conference. Twelfth IEEE International Conference on Micro Electro Mechanical Systems (Cat. No.99CH36291).

[101]  Jie Xu,et al.  Oscillating bubbles in teardrop cavities for microflow control , 2013 .

[102]  Kenneth R. Diller,et al.  Annual review of biomedical engineering , 1999 .

[103]  Rui F. Silva,et al.  Three-dimensional printed PCL-hydroxyapatite scaffolds filled with CNTs for bone cell growth stimulation. , 2016, Journal of biomedical materials research. Part B, Applied biomaterials.

[104]  Jie Xu,et al.  Oscillating bubbles: a versatile tool for lab on a chip applications. , 2012, Lab on a chip.

[105]  Jie Xu,et al.  Application of microfluidic “lab-on-a-chip” for the detection of mycotoxins in foods , 2015 .

[106]  D. Citterio,et al.  Inkjet-printed microfluidic multianalyte chemical sensing paper. , 2008, Analytical chemistry.

[107]  Yayue Pan,et al.  An integrated CNC accumulation system for automatic building-around-inserts , 2013 .

[108]  Ryan B. Wicker,et al.  Fabrication of 3D Biocompatible/Biodegradable Micro-Scaffolds Using Dynamic Mask Projection Microstereolithography , 2009 .

[109]  Han Wei Hou,et al.  Pinched flow coupled shear-modulated inertial microfluidics for high-throughput rare blood cell separation. , 2011, Lab on a chip.

[110]  Howard A. Stone,et al.  ENGINEERING FLOWS IN SMALL DEVICES , 2004 .

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

[112]  Lijun Song,et al.  Additive manufacturing by direct metal deposition , 2011 .

[113]  Wanhua Zhao,et al.  Novel stereolithography system for small size objects , 2006 .

[114]  C. L. Ventola Medical Applications for 3D Printing: Current and Projected Uses. , 2014, P & T : a peer-reviewed journal for formulary management.

[115]  Pál Ormos,et al.  Complex micromachines produced and driven by light , 2001, CLEO 2002.

[116]  Yayue Pan,et al.  Smooth surface fabrication in mask projection based stereolithography , 2012 .

[117]  Satoshi Kawata,et al.  Finer features for functional microdevices , 2001, Nature.

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

[119]  Chantal Khan Malek,et al.  Laser processing for bio-microfluidics applications (part I) , 2006 .

[120]  Youmin Hou,et al.  Recurrent filmwise and dropwise condensation on a beetle mimetic surface. , 2015, ACS nano.

[121]  N. Fleck,et al.  The structural performance of the periodic truss , 2006 .

[122]  Bethany C Gross,et al.  Evaluation of 3D printing and its potential impact on biotechnology and the chemical sciences. , 2014, Analytical chemistry.

[123]  Aldrik H. Velders,et al.  Simple 3D Printed Scaffold‐Removal Method for the Fabrication of Intricate Microfluidic Devices , 2015, Advanced science.

[124]  Jie Xu,et al.  Entry effects of droplet in a micro confinement: Implications for deformation-based circulating tumor cell microfiltration. , 2015, Biomicrofluidics.

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

[126]  Christopher J. Sutcliffe,et al.  Selective laser melting of high aspect ratio 3D nickel–titanium structures two way trained for MEMS applications , 2008 .

[127]  W. Ehrfeld,et al.  Recent developments in deep x-ray lithography , 1998 .

[128]  Ian Campbell,et al.  Additive manufacturing: rapid prototyping comes of age , 2012 .

[129]  K. Ren,et al.  Materials for microfluidic chip fabrication. , 2013, Accounts of chemical research.

[130]  G. Whitesides The origins and the future of microfluidics , 2006, Nature.

[131]  Aldrik H. Velders,et al.  Microfluidic Devices: Simple 3D Printed Scaffold‐Removal Method for the Fabrication of Intricate Microfluidic Devices (Adv. Sci. 9/2015) , 2015, Advanced Science.

[132]  Yong Chen,et al.  Multitool and Multi-Axis Computer Numerically Controlled Accumulation for Fabricating Conformal Features on Curved Surfaces , 2014 .

[133]  Satoshi Kawata,et al.  Two-photon-absorbed near-infrared photopolymerization for three-dimensional microfabrication , 1998 .

[134]  Seung Ki Moon,et al.  Inflatable wing design for micro UAVs using indirect 3D printing , 2014, 2014 11th International Conference on Ubiquitous Robots and Ambient Intelligence (URAI).

[135]  Yang Gao,et al.  Simultaneous additive and subtractive three-dimensional nanofabrication using integrated two-photon polymerization and multiphoton ablation , 2012, Light: Science & Applications.

[136]  Christopher B. Williams,et al.  Additive manufacturing of metallic cellular materials via three-dimensional printing , 2011 .

[137]  F. Rybicki,et al.  Medical 3D Printing for the Radiologist. , 2015, Radiographics : a review publication of the Radiological Society of North America, Inc.

[138]  R D Sochol,et al.  3D printed microfluidic circuitry via multijet-based additive manufacturing. , 2016, Lab on a chip.

[139]  Jie Xu,et al.  On the Quantification of Mixing in Microfluidics , 2014, Journal of laboratory automation.

[140]  H. Becker,et al.  Polymer microfluidic devices. , 2002, Talanta.

[141]  Liang Hou,et al.  Additive manufacturing and its societal impact: a literature review , 2013 .

[142]  C. Gärtner,et al.  Polymer microfabrication technologies , 2002 .

[143]  I Zein,et al.  Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modeling. , 2001, Journal of biomedical materials research.

[144]  Fang Qian,et al.  Light‐Directed Electrophoretic Deposition: A New Additive Manufacturing Technique for Arbitrarily Patterned 3D Composites , 2013, Advanced materials.

[145]  Jianzhong Fu,et al.  Printing 3D microfluidic chips with a 3D sugar printer , 2015 .

[146]  Jie Xu,et al.  Liquid metal robotics: a new category of soft robotics on the horizon , 2015 .

[147]  Xiaofeng Jia,et al.  Engineering anatomically shaped vascularized bone grafts with hASCs and 3D-printed PCL scaffolds. , 2014, Journal of biomedical materials research. Part A.

[148]  Hermann Seitz,et al.  A review on 3D micro-additive manufacturing technologies , 2012, The International Journal of Advanced Manufacturing Technology.

[149]  Costas Fotakis,et al.  Microfabrication by UV femtosecond laser ablation of Pt, Cr and indium oxide thin films , 1999 .

[150]  David W. Rosen,et al.  Additive Manufacturing Technologies: Rapid Prototyping to Direct Digital Manufacturing , 2009 .

[151]  Nicholas X. Fang,et al.  Projection micro-stereolithography using digital micro-mirror dynamic mask , 2005 .

[152]  David J Beebe,et al.  Micromilling: a method for ultra-rapid prototyping of plastic microfluidic devices. , 2015, Lab on a chip.

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

[154]  Jie Xu,et al.  Microfluidics “lab‐on‐a‐chip” system for food chemical hazard detection , 2014 .

[155]  G.-A. Racine,et al.  Microfabrication of 3D multidirectional inclined structures by UV lithography and electroplating , 1994, Proceedings IEEE Micro Electro Mechanical Systems An Investigation of Micro Structures, Sensors, Actuators, Machines and Robotic Systems.

[156]  Mohammad Hassan Saidi,et al.  A depthwise averaging solution for cross-stream diffusion in a Y-micromixer by considering thick electrical double layers and nonlinear rheology , 2015 .

[157]  D. Ivanov,et al.  Microfluidics in biotechnology , 2004, Journal of nanobiotechnology.

[158]  Mohammad Hassan Saidi,et al.  Electrokinetic mixing at high zeta potentials: ionic size effects on cross stream diffusion. , 2015, Journal of colloid and interface science.

[159]  Ming-Chuan Leu,et al.  Progress in Additive Manufacturing and Rapid Prototyping , 1998 .

[160]  A. Dimitrov,et al.  Design of a microfluidic device with a non-traditional flow profile for on-chip damage to zebrafish sensory cells , 2014 .

[161]  Kangsun Lee,et al.  Design of pressure-driven microfluidic networks using electric circuit analogy. , 2012, Lab on a chip.

[162]  Hansen Bow,et al.  Microfluidics for cell separation , 2010, Medical & Biological Engineering & Computing.

[163]  Wenming Liu,et al.  Microfluidics: a new cosset for neurobiology. , 2009, Lab on a chip.

[164]  Duc Truong Pham,et al.  A comparison of rapid prototyping technologies , 1998 .

[165]  Jean-Pierre Kruth,et al.  Material incress manufacturing by rapid prototyping techniques , 1991 .

[166]  Dimitris Drikakis,et al.  A hybrid molecular continuum method using point wise coupling , 2012, Adv. Eng. Softw..

[167]  Cheng Sun,et al.  Micro-stereolithography of polymeric and ceramic microstructures , 1999 .

[168]  Marshall Burns,et al.  Automated Fabrication: Improving Productivity in Manufacturing , 1993 .

[169]  P. Sarro,et al.  Surface versus bulk micromachining: the contest for suitable applications , 1998 .