Development of a biological detection platform utilizing a modular microfluidic stack

The goal of this project is to build a miniaturized, user-friendly cytometry setup (Datta et al. in Microfluidic platform for education and research. COMS, Baton Rouge, 2008; Frische et al. in Development of an miniaturized flow cytometry setup for visual cell inspection and sorting. Baton Rouge, Project Report, 2008) by combining a customized, microfluidic device with visual microscope inspection to detect and extract specific cells from a continuous sample flow. We developed a cytological tool, based on the Coulter particle counter principle, using a microelectrode array patterned on a borosilicate glass chip as electrical detection set-up which is fully embedded into a polymeric multi-layer microfluidic stack. The detection takes place between pairs of coplanar Cr/Au microelectrodes by sensing an impedance change caused by particles continuously carried within a microfluidic channel across the detection area under laminar flow conditions. A wide frequency range available for counting provides information on cell size, membrane capacitance, cytoplasm conductivity and is potentially of interest for in-depth cell diagnostic e.g. to detect damaged or cancerous cells and select them for extraction and further in-depth analysis.

[1]  K. Foster,et al.  Dielectric properties of tumor and normal tissues at radio through microwave frequencies. , 1981, The Journal of microwave power.

[2]  S. Gawad,et al.  Impedance spectroscopy flow cytometry: On‐chip label‐free cell differentiation , 2005, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[3]  Gang Liu,et al.  Study of PMMA thermal bonding , 2006 .

[4]  A. M. F. Neto,et al.  Impedance spectroscopy analysis of an electrolytic cell limited by Ohmic electrodes: The case of ions with two different diffusion coefficients dispersed in an aqueous solution , 2007 .

[5]  H. Schwan,et al.  Electrical properties of phospholipid vesicles. , 1970, Biophysical journal.

[6]  D. Holmes,et al.  AC electrokinetic focussing in microchannels: micro- and nanoparticles , 2003 .

[7]  Jost Goettert,et al.  Development of an Integrated Polymer Microfluidic Stack , 2006 .

[8]  J. Gimsa,et al.  A unified resistor-capacitor model for impedance, dielectrophoresis, electrorotation, and induced transmembrane potential. , 1998, Biophysical journal.

[9]  Yong-Sang Kim,et al.  Microfabricated in-channel structured polydimethylsiloxane microfluidic system for a lab-on-a-chip. , 2008, Journal of Nanoscience and Nanotechnology.

[10]  S Potgieter,et al.  Microfluidic devices for biological applications , 2010 .

[11]  Thayne L Edwards,et al.  Multi-layer plastic/glass microfluidic systems containing electrical and mechanical functionality. , 2003, Lab on a chip.

[12]  Urban Seger,et al.  Dielectric spectroscopy in a micromachined flow cytometer: theoretical and practical considerations. , 2004, Lab on a chip.

[13]  S. Takayama,et al.  Microfluidics for flow cytometric analysis of cells and particles , 2005, Physiological measurement.

[14]  Yoshiki Sasai,et al.  Fluorescence‐Activated Cell Sorting–Based Purification of Embryonic Stem Cell–Derived Neural Precursors Averts Tumor Formation after Transplantation , 2006, Stem cells.

[15]  S. Gawad,et al.  Single cell dielectric spectroscopy , 2007 .

[16]  Hee Chan Kim,et al.  Recent advances in miniaturized microfluidic flow cytometry for clinical use , 2007, Electrophoresis.

[17]  Hywel Morgan,et al.  Broadband single cell impedance spectroscopy using maximum length sequences: theoretical analysis and practical considerations , 2007 .

[18]  R. Rabbitt,et al.  A Multilayer MEMS Platform for Single-Cell Electric Impedance Spectroscopy and Electrochemical Analysis , 2008, Journal of Microelectromechanical Systems.

[19]  P. Abgrall,et al.  Lab-on-chip technologies: making a microfluidic network and coupling it into a complete microsystem—a review , 2007 .

[20]  K. Sekine Application of boundary element method to calculation of the complex permittivity of suspensions of cells in shape of Dinfinityh symmetry. , 2000, Bioelectrochemistry.

[21]  Mark M. Stecker,et al.  Electrical Properties of Metal Microelectrodes , 2000 .

[22]  D. Robinson,et al.  The electrical properties of metal microelectrodes , 1968 .

[23]  Ciprian Iliescu,et al.  A microfluidic device for impedance spectroscopy analysis of biological samples , 2007 .

[24]  Holger Becker,et al.  Polymer microfabrication technologies for microfluidic systems , 2008, Analytical and bioanalytical chemistry.

[25]  S. Gawad,et al.  Micromachined impedance spectroscopy flow cytometer for cell analysis and particle sizing. , 2001, Lab on a chip.

[26]  J. Cooper,et al.  Fabrication of robust 2-D and 3-D microfluidic networks for lab-on-a-chip bioassays , 2005, Journal of Microelectromechanical Systems.

[27]  E. McAdams,et al.  The linear and non-linear electrical properties of the electrode-electrolyte interface , 1995 .

[28]  Bruce K. Gale,et al.  Determining the optimal PDMS–PDMS bonding technique for microfluidic devices , 2008 .

[29]  Roland Zengerle,et al.  Microfluidic platforms for lab-on-a-chip applications. , 2007, Lab on a chip.

[30]  Microfluidic lab-on-a-chip for microbial identification on a DNA microarray , 2007 .