Hydrodynamic gating for sample introduction on a microfluidic chip.

We present a microfluidic sample introduction approach based on a novel flow control mechanism, hydrodynamic gated injection. It has the advantages of easy and flexible flow control, similar to its analog, electrokinetic gated injection, but exhibits the unique properties of strong driving force and good biocompatibility, ideal for applications involving live biological samples. Theories for hydrodynamic gating were proposed and validated by both numerical simulations and flow visualization experiments. An investigation with fluorescein revealed that pico-liter samples can be injected with high repeatability (RSD <1.9%). Selective injections of GFP-transfected nematode eggs were demonstrated with a survival rate of >95%. We expect the developed method to be potentially useful for microfluidic cell and organism analysis, either as a sample introduction module or a stand-alone analyzer.

[1]  J. Qin,et al.  Maze exploration and learning in C. elegans. , 2007, Lab on a chip.

[2]  S. Brenner The genetics of Caenorhabditis elegans. , 1974, Genetics.

[3]  W. Wood The Nematode Caenorhabditis elegans , 1988 .

[4]  Shaheynoor Talukder,et al.  Genome-wide analysis of ETS-family DNA-binding in vitro and in vivo , 2010, The EMBO journal.

[5]  A. Manz,et al.  Micro total analysis systems. Latest advancements and trends. , 2006, Analytical chemistry.

[6]  Qingming Luo,et al.  Microfluidic chip: next-generation platform for systems biology. , 2009, Analytica chimica acta.

[7]  Bo Huang,et al.  Counting Low-Copy Number Proteins in a Single Cell , 2007, Science.

[8]  N. Allbritton,et al.  Chemical analysis of single cells. , 2008, Annual review of analytical chemistry.

[9]  C. Culbertson,et al.  Static and dynamic acute cytotoxicity assays on microfluidic devices. , 2005, Analytical chemistry.

[10]  J. Michael Ramsey,et al.  Microchip Capillary Electrophoresis with an Integrated Postcolumn Reactor , 1994 .

[11]  Axel Scherer,et al.  A microfluidic processor for gene expression profiling of single human embryonic stem cells. , 2008, Lab on a chip.

[12]  R. Waterston,et al.  The Nematode Caenorhabditis elegans and Its Genome , 1995, Science.

[13]  J. Apfeld,et al.  A microfabricated array of clamps for immobilizing and imaging C. elegans. , 2007, Lab on a chip.

[14]  J. Rocca,et al.  Electrokinetic‐based injection modes for separative microsystems , 2008, Electrophoresis.

[15]  Supplementary Material (ESI) for Lab on a Chip This journal is © The Royal Society of Chemistry 2009 Analysis of the kinetic behavior of chains and clusters , 2008 .

[16]  Bifeng Liu,et al.  Characterization of electrokinetic gating valve in microfluidic channels. , 2007, Analytica chimica acta.

[17]  Matthew M. Crane,et al.  Automated on-chip rapid microscopy, phenotyping and sorting of C. elegans , 2008, Nature Methods.

[18]  A. Kummrow,et al.  Microfluidic structures for flow cytometric analysis of hydrodynamically focussed blood cells fabricated by ultraprecision micromachining. , 2009, Lab on a chip.

[19]  B. Bainbridge,et al.  Genetics , 1981, Experientia.

[20]  Andreas Manz,et al.  Micro total analysis systems: latest achievements. , 2008, Analytical chemistry.

[21]  Mehmet Fatih Yanik,et al.  Microfluidic system for on-chip high-throughput whole-animal sorting and screening at subcellular resolution , 2007, Proceedings of the National Academy of Sciences.

[22]  R. Zare,et al.  Chemical cytometry on a picoliter-scale integrated microfluidic chip. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[23]  H. Kitano Systems Biology: A Brief Overview , 2002, Science.

[24]  Marc W Kirschner,et al.  The Meaning of Systems Biology , 2005, Cell.

[25]  K. Cottingham Systems biology: a boon for analytical chemists? , 2005, Analytical chemistry.

[26]  J. Michael Ramsey,et al.  Precolumn Reactions with Electrophoretic Analysis Integrated on a Microchip , 1994 .

[27]  K. Jensen,et al.  Cells on chips , 2006, Nature.

[28]  Nancy L Allbritton,et al.  CRITICAL REVIEW www.rsc.org/loc | Lab on a Chip Analysis of single mammalian cells on-chip , 2006 .

[29]  G. Whitesides,et al.  Microfabrication meets microbiology , 2007, Nature Reviews Microbiology.

[30]  Deirdre R. Meldrum,et al.  Life-on-a-chip , 2003, Nature Reviews Microbiology.

[31]  J. Rossier,et al.  Integrating whole transcriptome assays on a lab-on-a-chip for single cell gene profiling. , 2008, Lab on a chip.

[32]  Luke P. Lee,et al.  Microfluidics-based systems biology. , 2006, Molecular bioSystems.

[33]  A. Aderem Systems Biology: Its Practice and Challenges , 2005, Cell.

[34]  Wen-Bin Du,et al.  High-throughput nanoliter sample introduction microfluidic chip-based flow injection analysis system with gravity-driven flows. , 2005, Analytical chemistry.