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May 2013

Volume 7, Issue 3 (partial)

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Ionic current devices—Recent progress in the merging of electronic, microfluidic, and biomimetic structures

Hyung-Jun Koo and Orlin D. Velev

Biomicrofluidics 7, 031501 (2013); http://dx.doi.org/10.1063/1.4804249 (10 pages)

Online Publication Date: 9 May 2013

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We review the recent progress in the emerging area of devices and circuits operating on the basis of ionic currents. These devices operate at the intersection of electrochemistry, electronics, and microfluidics, and their potential applications are inspired by essential biological processes such as neural transmission. Ionic current rectification has been demonstrated in diode-like devices containing electrolyte solutions, hydrogel, or hydrated nanofilms. More complex functions have been realized in ionic current based transistors, solar cells, and switching memory devices. Microfluidic channels and networks—an intrinsic component of the ionic devices—could play the role of wires and circuits in conventional electronics.
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85.85.+j Micro- and nano-electromechanical systems (MEMS/NEMS) and devices
87.80.Ek Mechanical and micromechanical techniques
87.85.Ox Biomedical instrumentation and transducers, including micro-electro-mechanical systems (MEMS)
47.85.Np Fluidics
47.61.Fg Flows in micro-electromechanical systems (MEMS) and nano-electromechanical systems (NEMS)
07.10.Cm Micromechanical devices and systems
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A hybrid microfluidic platform for cell-based assays via diffusive and convective trans-membrane perfusion

Elizaveta Vereshchagina, Declan Mc Glade, Macdara Glynn, and Jens Ducrée

Biomicrofluidics 7, 034101 (2013); http://dx.doi.org/10.1063/1.4804250 (14 pages)

Online Publication Date: 8 May 2013

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We present a novel 3D hybrid assembly of a polymer microfluidic chip with polycarbonate track-etched membrane (PCTEM) enabling membrane-supported cell culture. Two chip designs have been developed to establish either diffusive or convective reagent delivery using the integrated PCTEM. While it is well suited to a range of cell-based assays, we specifically employ this platform for the screening of a common antitumor chemotoxic agent (mitomycin C – MMC) on the HL60 myeloid leukemia cell line. The toxic activity of MMC is based on the generation of severe DNA damage in the cells. Using either mode of operation, the HL60 cells were cultured on-chip before, during, and after exposure to MMC at concentrations ranging from 0 to 50 μM. Cell viability was analysed off-chip by the trypan blue dye exclusion assay. The results of the on-chip viability assay were found to be consistent with those obtained off-chip and indicated ca. 40% cell survival at MMC concentration of 50 μM. The catalogue of capabilities of the here described cell assay platform comprises of (i) the culturing of cells either under shear-free conditions or under induced through-membrane flows, (ii) the tight time control of the reagent exposure, (iii) the straightforward assembly of devices, (iv) the flexibility on the choice of the membrane, and, prospectively, (v) the amenability for large-scale parallelization.
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87.85.Ox Biomedical instrumentation and transducers, including micro-electro-mechanical systems (MEMS)
47.85.-g Applied fluid mechanics
87.16.-b Subcellular structure and processes
87.19.xj Cancer

Viscoelasticity of blood and viscoelastic blood analogues for use in polydymethylsiloxane in vitro models of the circulatory system

Laura Campo-Deaño, Roel P. A. Dullens, Dirk G. A. L. Aarts, Fernando T. Pinho, and Mónica S. N. Oliveira

Biomicrofluidics 7, 034102 (2013); http://dx.doi.org/10.1063/1.4804649 (11 pages)

Online Publication Date: 17 May 2013

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The non-Newtonian properties of blood are of great importance since they are closely related with incident cardiovascular diseases. A good understanding of the hemodynamics through the main vessels of the human circulatory system is thus fundamental in the detection and especially in the treatment of these diseases. Very often such studies take place in vitro for convenience and better flow control and these generally require blood analogue solutions that not only adequately mimic the viscoelastic properties of blood but also minimize undesirable optical distortions arising from vessel curvature that could interfere in flow visualizations or particle image velocimetry measurements. In this work, we present the viscoelastic moduli of whole human blood obtained by means of passive microrheology experiments. These results and existing shear and extensional rheological data for whole human blood in the literature enabled us to develop solutions with rheological behavior analogous to real whole blood and with a refractive index suited for PDMS (polydymethylsiloxane) micro- and milli-channels. In addition, these blood analogues can be modified in order to obtain a larger range of refractive indices from 1.38 to 1.43 to match the refractive index of several materials other than PDMS.
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87.19.U- Hemodynamics
47.63.Cb Blood flow in cardiovascular system
87.85.gf Fluid mechanics and rheology

Simulation of single DNA molecule stretching and immobilization in a de-wetting two-phase flow over micropillar-patterned surface

Wei-Ching Liao, Xin Hu, Weixiong Wang, and L. James Lee

Biomicrofluidics 7, 034103 (2013); http://dx.doi.org/10.1063/1.4807462 (16 pages)

Online Publication Date: 21 May 2013

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We investigate single DNA stretching dynamics in a de-wetting flow over micropillars using Brownian dynamics simulation. The Brownian dynamics simulation is coupled with transient flow field computation through a numerical particle tracking algorithm. The droplet formation on the top of the micropillar during the de-wetting process creates a flow pattern that allows DNA to stretch across the micropillars. It is found that DNA nanowire forms if DNA molecules could extend across the stagnation point inside the connecting water filament before its breakup. It also shows that DNA locates closer to the top wall of the micropillar has higher chance to enter the flow pattern of droplet formation and thus has higher chance to be stretched across the micropillars. Our simulation tool has the potential to become a design tool for DNA manipulation in complex biomicrofluidic devices.
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87.80.Ek Mechanical and micromechanical techniques
47.63.-b Biological fluid dynamics
85.85.+j Micro- and nano-electromechanical systems (MEMS/NEMS) and devices
87.14.gk DNA
87.19.rh Fluid transport and rheology

Continuous flowing micro-reactor for aqueous reaction at temperature higher than 100 °C

Fei Xie, Baojun Wang, Wei Wang, Tian Dong, Jianhua Tong, Shanhong Xia, Wengang Wu, and Zhihong Li

Biomicrofluidics 7, 034104 (2013); http://dx.doi.org/10.1063/1.4807463 (8 pages)

Online Publication Date: 21 May 2013

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Some aqueous reactions in biological or chemical fields are accomplished at a high temperature. When the reaction temperature is higher than 100 °C, an autoclave reactor is usually required to elevate the boiling point of the water by creating a high-pressure environment in a closed system. This work presented an alternative continuous flowing microfluidic solution for aqueous reaction with a reaction temperature higher than 100 °C. The pressure regulating function was successfully fulfilled by a small microchannel based on a delicate hydrodynamic design. Combined with micro heater and temperature sensor that integrated in a single chip by utilizing silicon-based microfabrication techniques, this pressure regulating microchannel generated a high-pressure/high-temperature environment in the upstream reaction zone when the reagents continuously flow through the chip. As a preliminary demonstration, thermal digestion of aqueous total phosphorus sample was achieved in this continuous flowing micro-reactor at a working pressure of 990 kPa (under the working flow rate of 20 nl/s) along with a reaction temperature of 145 °C. This continuous flowing microfluidic solution for high-temperature reaction may find applications in various micro total analysis systems.
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87.80.Ek Mechanical and micromechanical techniques
07.10.Cm Micromechanical devices and systems
47.80.Fg Pressure and temperature measurements
47.85.Dh Hydrodynamics, hydraulics, hydrostatics
47.85.Np Fluidics
85.85.+j Micro- and nano-electromechanical systems (MEMS/NEMS) and devices

Direct detection of cancer biomarkers in blood using a “place n play” modular polydimethylsiloxane pump

Honglian Zhang, Gang Li, Lingying Liao, HongJu Mao, Qinghui Jin, and Jianlong Zhao

Biomicrofluidics 7, 034105 (2013); http://dx.doi.org/10.1063/1.4807803 (10 pages)

Online Publication Date: 23 May 2013

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Cancer biomarkers have significant potential as reliable tools for the early detection of the disease and for monitoring its recurrence. However, most current methods for biomarker detection have technical difficulties (such as sample preparation and specific detector requirements) which limit their application in point of care diagnostics. We developed an extremely simple, power-free microfluidic system for direct detection of cancer biomarkers in microliter volumes of whole blood. CEA and CYFRA21-1 were chosen as model cancer biomarkers. The system automatically extracted blood plasma from less than 3 μl of whole blood and performed a multiplex sample-to-answer assay (nano-ELISA (enzyme-linked immunosorbent assay) technique) without the use of external power or extra components. By taking advantage of the nano-ELISA technique, this microfluidic system detected CEA at a concentration of 50 pg/ml and CYFRA21-1 at a concentration of 60 pg/ml within 60 min. The combination of PnP polydimethylsiloxane (PDMS) pump and nano-ELISA technique in a single microchip system shows great promise for the detection of cancer biomarkers in a drop of blood.
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87.85.Ox Biomedical instrumentation and transducers, including micro-electro-mechanical systems (MEMS)
87.85.Va Micromachining
47.85.-g Applied fluid mechanics
85.85.+j Micro- and nano-electromechanical systems (MEMS/NEMS) and devices
87.80.Ek Mechanical and micromechanical techniques
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