Droplet Microfluidics for Chip-Based Diagnostics

Droplet microfluidics (DMF) is a fluidic handling technology that enables precision control over dispensing and subsequent manipulation of droplets in the volume range of microliters to picoliters, on a micro-fabricated device. There are several different droplet actuation methods, all of which can generate external stimuli, to either actively or passively control the shape and positioning of fluidic droplets over patterned substrates. In this review article, we focus on the operation and utility of electro-actuation-based DMF devices, which utilize one or more micro-/nano-patterned substrates to facilitate electric field-based handling of chemical and/or biological samples. The underlying theory of DMF actuations, device fabrication methods and integration of optical and opto-electronic detectors is discussed in this review. Example applications of such electro-actuation-based DMF devices have also been included, illustrating the various actuation methods and their utility in conducting chip-based laboratory and clinical diagnostic assays.

[1]  Mark Lazari,et al.  Radiolabelling diverse positron emission tomography (PET) tracers using a single digital microfluidic reactor chip. , 2014, Lab on a chip.

[2]  A. A. Darhuber,et al.  Planar digital nanoliter dispensing system based on thermocapillary actuation. , 2010, Lab on a chip.

[3]  Peter Enoksson,et al.  Towards an electrowetting-based digital microfluidic platform for magnetic immunoassays. , 2009, Lab on a chip.

[4]  C. Kim,et al.  Direct-Referencing Two-Dimensional-Array Digital Microfluidics Using Multilayer Printed Circuit Board , 2008, Journal of Microelectromechanical Systems.

[5]  Ronald W Davis,et al.  Simulation and fabrication of a new novel 3D injectable biosensor for high throughput genomics and proteomics in a lab-on-a-chip device , 2013, Nanotechnology.

[6]  H. A. Pohl,et al.  Dielectrophoresis: The Behavior of Neutral Matter in Nonuniform Electric Fields , 1978 .

[7]  R. Fair,et al.  Dynamics of electro-wetting droplet transport , 2002 .

[8]  M. Tabrizian,et al.  Nanostructured digital microfluidics for enhanced surface plasmon resonance imaging. , 2011, Biosensors & bioelectronics.

[9]  G McHale,et al.  Nano-scale superhydrophobicity: suppression of protein adsorption and promotion of flow-induced detachment. , 2008, Lab on a chip.

[10]  Johannes Czernin,et al.  Efficient Radiosynthesis of 3′-Deoxy-3′-18F-Fluorothymidine Using Electrowetting-on-Dielectric Digital Microfluidic Chip , 2014, The Journal of Nuclear Medicine.

[11]  H. S. Wolff,et al.  iRun: Horizontal and Vertical Shape of a Region-Based Graph Compression , 2022, Sensors.

[12]  Thomas B. Jones,et al.  Size-selective deposition of particles combining liquid and particulate dielectrophoresis , 2005 .

[13]  Aaron R Wheeler,et al.  A digital microfluidic approach to heterogeneous immunoassays , 2011, Analytical and bioanalytical chemistry.

[14]  Martin A M Gijs,et al.  On-chip immunoassay using electrostatic assembly of streptavidin-coated bead micropatterns. , 2009, Analytical chemistry.

[15]  V. Srinivasan,et al.  Heterogeneous immunoassays using magnetic beads on a digital microfluidic platform. , 2008, Lab on a chip.

[16]  H. A. Pohl,et al.  Some Effects of Nonuniform Fields on Dielectrics , 1958 .

[17]  Ravi Prakash,et al.  DEP actuation of emulsion jets and dispensing of sub-nanoliter emulsion droplets. , 2009, Lab on a chip.

[18]  Philippe Dubois,et al.  Actuation potentials and capillary forces in electrowetting based microsystems , 2007 .

[19]  Karan V. I. S. Kaler,et al.  Droplet Microfluidic Chip Based Nucleic Acid Amplification and Real-Time Detection of Influenza Viruses , 2013, Journal of the Electrochemical Society.

[20]  Karan V. I. S. Kaler,et al.  Liquid dielectrophoresis dispensing of vesicles for on-chip nucleic acid isolation and detection , 2013 .

[21]  Jason Heikenfeld,et al.  Reliable and Low-Voltage Electrowetting on Thin Parylene Films , 2011 .

[22]  Vinayak Rastogi,et al.  Development and evaluation of realistic microbioassays in freely suspended droplets on a chip. , 2007, Biomicrofluidics.

[23]  Mehdi Javanmard,et al.  Microneedle Biosensor: A Method for Direct Label-free Real Time Protein Detection. , 2013, Sensors and actuators. B, Chemical.

[24]  M. Wash Electrostatic Actuation of Liquid Droplets for Micro-Reactor Applications , 1997 .

[25]  Sigurd Wagner,et al.  Thermocapillary actuation of droplets on chemically patterned surfaces by programmable microheater arrays , 2003 .

[26]  Aaron R Wheeler,et al.  Electrowetting-based microfluidics for analysis of peptides and proteins by matrix-assisted laser desorption/ionization mass spectrometry. , 2004, Analytical chemistry.

[27]  A. Wheeler,et al.  A digital microfluidic approach to proteomic sample processing. , 2009, Analytical Chemistry.

[28]  Achim Wixforth,et al.  Acoustically Driven Programmable Microfluidics for Biological and Chemical Applications , 2006 .

[29]  Rustem F Ismagilov,et al.  Microfluidics using spatially defined arrays of droplets in one, two, and three dimensions. , 2011, Annual review of analytical chemistry.

[30]  Zhiguang Guo,et al.  “Stick and slide” ferrofluidic droplets on superhydrophobic surfaces , 2006 .

[31]  Teodor Veres,et al.  Two-dimensional droplet-based surface plasmon resonance imaging using electrowetting-on-dielectric microfluidics. , 2009, Lab on a chip.

[32]  Ravi Prakash,et al.  Liquid dielectrophoresis and surface microfluidics. , 2010, Biomicrofluidics.

[33]  J. Baret,et al.  Electrowetting: from basics to applications , 2005 .

[34]  M. Washizu Electrostatic actuation of liquid droplets for micro-reactor applications , 1997 .

[35]  Hyejin Moon,et al.  On-chip drop-to-drop liquid microextraction coupled with real-time concentration monitoring technique. , 2011, Analytical chemistry.

[36]  K. Frazer,et al.  Microdroplet-based PCR amplification for large scale targeted sequencing , 2009, Nature Biotechnology.

[37]  R. Fair,et al.  Electrowetting-based actuation of liquid droplets for microfluidic applications , 2000 .

[38]  Hiroshi Toshiyoshi,et al.  Light actuation of liquid by optoelectrowetting , 2003 .

[39]  S. Cho,et al.  Creating, transporting, cutting, and merging liquid droplets by electrowetting-based actuation for digital microfluidic circuits , 2003 .

[40]  A. Wixforth,et al.  Planar chip device for PCR and hybridization with surface acoustic wave pump. , 2005, Lab on a chip.

[41]  Shih-Kang Fan,et al.  Recoverable electrowetting-on-dielectric device in chemiluminescence enzymatic detector , 2014 .

[42]  Chang-Jin C J Kim,et al.  All-electronic droplet generation on-chip with real-time feedback control for EWOD digital microfluidics. , 2008, Lab on a chip.

[43]  Adisorn Tuantranont,et al.  Electrochemical detection on electrowetting-on-dielectric digital microfluidic chip. , 2011, Talanta.

[44]  Aaron R Wheeler,et al.  Pluronic additives: a solution to sticky problems in digital microfluidics. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[45]  Sung Kwon Cho,et al.  Microparticle Concentration and Separation by Traveling-Wave Dielectrophoresis (twDEP) for Digital Microfluidics , 2007, Journal of Microelectromechanical Systems.

[46]  Jeong‐Yeol Yoon,et al.  Preventing Biomolecular Adsorption in Electrowetting-Based Biofluidic Chips. , 2003, Analytical chemistry.

[47]  M. Tabrizian,et al.  Biochip functionalization using electrowetting-on-dielectric digital microfluidics for surface plasmon resonance imaging detection of DNA hybridization. , 2009, Biosensors & bioelectronics.

[48]  T. G. Mitchell,et al.  Multiplexed real-time polymerase chain reaction on a digital microfluidic platform. , 2010, Analytical chemistry.

[49]  C. Kim,et al.  An integrated digital microfluidic chip for multiplexed proteomic sample preparation and analysis by MALDI-MS. , 2006, Lab on a chip.

[50]  Jr-Lung Lin,et al.  Integrated polymerase chain reaction chips utilizing digital microfluidics , 2006, Biomedical microdevices.

[51]  A. Wheeler,et al.  Paper Microfluidics Goes Digital , 2014, Advanced materials.

[52]  Dimitrios P. Papageorgiou,et al.  Performance of multilayered fluoropolymer surface coating for DEP surface microfluidic devices , 2012 .

[53]  J. Lammertyn,et al.  A highly efficient extraction protocol for magnetic particles on a digital microfluidic chip , 2014 .

[54]  Aaron R Wheeler,et al.  A world-to-chip interface for digital microfluidics. , 2009, Analytical chemistry.

[55]  G. Johansson,et al.  A Feasibility Study of a Capacitive Biosensor for Direct Detection of DNA Hybridization , 1999 .

[56]  A. Theberge,et al.  Microdroplets in microfluidics: an evolving platform for discoveries in chemistry and biology. , 2010, Angewandte Chemie.

[57]  Karan V. I. S. Kaler,et al.  Multiplex, Quantitative, Reverse Transcription PCR Detection of Influenza Viruses Using Droplet Microfluidic Technology , 2014, Micromachines.

[58]  A. Wheeler,et al.  Digital microfluidic method for protein extraction by precipitation. , 2009, Analytical chemistry.

[59]  Jack Zhou,et al.  Chemical and Biological Applications of Digital-Microfluidic Devices , 2007, IEEE Design & Test of Computers.

[60]  Aaron Wheeler,et al.  Putting Electrowetting to Work , 2008, Science.

[61]  R. Garrell,et al.  Droplet-based microfluidics with nonaqueous solvents and solutions. , 2006, Lab on a chip.

[62]  Y. Fouillet,et al.  Ionic liquid droplet as e-microreactor. , 2006, Analytical chemistry.

[63]  R. Fair,et al.  Picoliter DNA sequencing chemistry on an electrowetting-based digital microfluidic platform. , 2011, Biotechnology journal.

[64]  R. Garrell,et al.  Integration of protein processing steps on a droplet microfluidics platform for MALDI-MS analysis. , 2010, Analytical chemistry.

[65]  Andreas G. Boudouvis,et al.  Evaluating the Robustness of Top Coatings Comprising Plasma-Deposited Fluorocarbons in Electrowetting Systems , 2011 .

[66]  M.C. Wu,et al.  Droplet Manipulation With Light on Optoelectrowetting Device , 2008, Journal of Microelectromechanical Systems.

[67]  Karan V. I. S. Kaler,et al.  Liquid DEP actuation and precision dispensing of variable volume droplets. , 2010, Lab on a chip.

[68]  A. Wheeler,et al.  Synchronized synthesis of peptide-based macrocycles by digital microfluidics. , 2010, Angewandte Chemie.

[69]  Aaron R Wheeler,et al.  Hydrogel discs for digital microfluidics. , 2012, Biomicrofluidics.

[70]  Joonwon Kim,et al.  Using EWOD (electrowetting-on-dielectric) actuation in a micro conveyor system , 2005, The 13th International Conference on Solid-State Sensors, Actuators and Microsystems, 2005. Digest of Technical Papers. TRANSDUCERS '05..

[71]  O. Velev,et al.  Anisotropic particle synthesis in dielectrophoretically controlled microdroplet reactors , 2004, Nature materials.

[72]  T. Jones,et al.  Frequency-dependent electromechanics of aqueous liquids: electrowetting and dielectrophoresis. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[73]  Vijay Srinivasan,et al.  Development of a digital microfluidic platform for point of care testing. , 2008, Lab on a chip.

[74]  N.M. Jokerst,et al.  Integrated Optical Sensor in a Digital Microfluidic Platform , 2008, IEEE Sensors Journal.

[75]  Karan V. I. S. Kaler,et al.  Microbead dispensing and ultralow DNA hybridization detection using liquid dielectrophoresis , 2012 .

[76]  Aaron R Wheeler,et al.  A feedback control system for high-fidelity digital microfluidics. , 2011, Lab on a chip.

[77]  T. B. Jones Dynamics of Dielectrophoretic Liquid Microactuation , 2001 .

[78]  R. Fair,et al.  An integrated digital microfluidic lab-on-a-chip for clinical diagnostics on human physiological fluids. , 2004, Lab on a chip.

[79]  Gengfeng Zheng,et al.  Multiplexed electrical detection of cancer markers with nanowire sensor arrays , 2005, Nature Biotechnology.

[80]  Karan V. I. S. Kaler,et al.  Dielectrophoretic liquid actuation on nano-textured super hydrophobic surfaces , 2013 .

[81]  Joseph A Loo,et al.  Incubated protein reduction and digestion on an electrowetting-on-dielectric digital microfluidic chip for MALDI-MS. , 2010, Analytical chemistry.

[82]  S. Cho,et al.  Low voltage electrowetting-on-dielectric , 2002 .

[83]  T. Jones Liquid dielectrophoresis on the microscale , 2001 .

[84]  Karan V. I. S. Kaler,et al.  Quantitative DNA Hybridization Assay on a Multiplexed Surface Microfluidic Device , 2009 .

[85]  S. T. Picraux,et al.  Magnetic movement of biological fluid droplets , 2007 .

[86]  Jason Heikenfeld,et al.  Detailed analysis of defect reduction in electrowetting dielectrics through a two-layer ‘barrier’ approach , 2013 .

[87]  Thomas B. Jones,et al.  On the Relationship of Dielectrophoresis and Electrowetting , 2002 .

[88]  R. Garrell,et al.  Electromechanical model for actuating liquids in a two-plate droplet microfluidic device. , 2009, Lab on a chip.

[89]  S. Nugen,et al.  A hybrid paper and microfluidic chip with electrowetting valves and colorimetric detection. , 2014, The Analyst.

[90]  K. Shin,et al.  Active Digital Microfluidic Paper Chips with Inkjet‐Printed Patterned Electrodes , 2014, Advanced materials.

[91]  C. Kim,et al.  Digital microfluidics with in-line sample purification for proteomics analyses with MALDI-MS. , 2005, Analytical chemistry.