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Vashist S.K.,Institute For Mikro Und Informationstechnik | Vashist S.K.,Albert Ludwigs University of Freiburg | Lam E.,National Research Council Canada | Hrapovic S.,National Research Council Canada | And 2 more authors.
Chemical Reviews | Year: 2014

Biosensing and diagnostic platforms with high sensitivity, specificity, and fast response time are based on immobilized biomolecules such as antibodies (Abs), aptamers, enzymes, nucleic acids, receptors, and whole cells for the detection of target analytes. Such sensing biomolecules should be bound to the surface of a signal transducer with a required specific chemical, electrical, or optical property. The biological recognition event generates a quantifiable signal, which is equated to the amount or concentration of the analyte. APTES can be deposited on solid materials, electrode materials, nanomaterials, and nanocomposites under variable conditions of concentration, solvent, temperature, and time. In addition, curing conditions such as air/heat drying might be necessary depending upon the intended application. Pertinent information on the thickness, morphology, and conformation of the APTES layer reported in the literature is often different and conflicting.


Vashist S.K.,Institute For Mikro Und Informationstechnik | Vashist S.K.,Albert Ludwigs University of Freiburg | Schneider E.M.,University of Ulm | Luong J.H.T.,University College Cork
Analyst | Year: 2014

This article describes a highly-sensitive surface plasmon resonance (SPR)-based immunoassay (IA) for human fetuin A (HFA), a specific biomarker for atherosclerosis and hepatocellular carcinoma. The assay is based on a novel immobilization procedure that simply involves the dilution of an anti-HFA capture antibody (Ab) in 1% (v/v) 3-aminopropyltriethoxysilane (APTES), followed by its dispensing on a KOH-treated gold (Au)-coated SPR chip and incubation for 30 min. The developed SPR IA detected 0.3-20 ng mL-1 of HFA with a limit of detection and sensitivity of 0.7 ng mL-1 and 1 ng mL -1, respectively. The highly-simplified Ab immobilization procedure is also 5-fold more rapid than conventional procedures. It leads to the leach-proof binding of the capture Ab, which means that the developed SPR IA is highly cost-effective, as the Ab-bound SPR chip could be reused for many repeated HFA IAs after regeneration with 10 mM glycine-HCl, pH 2.0. The Ab-bound SPR chip, stored at 4 °C, lost only 18% of its original activity after 4 months. For the detection of HFA spiked in diluted human whole blood and plasma, the results obtained by the developed SPR IA agreed well with the commercial HFA sandwich ELISA. This journal is © the Partner Organisations 2014.


Hutzenlaub T.,Institute For Mikro Und Informationstechnik | Thiele S.,Albert Ludwigs University of Freiburg | Paust N.,Institute For Mikro Und Informationstechnik | Spotnitz R.,Battery Design LLC | And 3 more authors.
Electrochimica Acta | Year: 2014

We combine a three-phase, three-dimensional reconstruction of a LiCoO 2 battery cathode based on focused ion-beam/scanning electron microscopy (FIB/SEM) imaging with an electrochemical model. The model considers the electric potential and lithium/salt concentration distribution in both the liquid electrolyte and the solid active-material phases. In contrast to previously presented models, we spatially resolve the carbon-binder phase to provide a more realistic description of the electric potential. We observe that carbon-binder coverage of the solid electrolyte interface (SEI) impedes local surface reactions and thus affects lithium redistribution. For the considered cathode, the total surface to volume ratio of the SEI is reduced from 11.2 × 105 to 6.5 × 105 m2 m -3 when the carbon-binder phase is modelled explicitly. This leads to increased inhomogeneity of the lithium concentration in active-material grains during charging. Additionally, we study lithium/salt concentration in the electrolyte, revealing gradients between 0.9 and 1.5 kmol m-3 depending on the distance to the separator. This is significant because the lithium/salt concentration directly affects the ion transport properties of the electrolyte. © 2013 Elsevier Ltd. All rights reserved.


Mohamed S.A.,Albert Ludwigs University of Freiburg | Manoli Y.,Institute For Mikro Und Informationstechnik
Proceedings - IEEE International Symposium on Circuits and Systems | Year: 2015

A voltage-controlled oscillator (VCO) with low phase noise and low power dissipation for sub-harmonic mixing is proposed. A cross-coupled negativeresistance circuit with nMOS transistors in the feedback is adopted to suppress high-order harmonics. According to this proposed structure, low phase noise can be achieved under low power dissipation. The VCO chip including a cross-coupled differential buffers (not shown in this work) is implemented in 0.13μm CMOS process under a supply voltage of 1.2V and consumes a total power of 0.5 mW. The measured results show that the VCO with integrated buffers at 1 MH offset frequency has a phase noise of -138 dBc/Hz. The proposed design has a wide tuning range of 380-420 MHz under the tuning voltage of 0-1.2V power supply voltage. © 2015 IEEE.


Kalkandjiev K.,Albert Ludwigs University of Freiburg | Riegger L.,BioFluidix GmbH | Kosse D.,Institute For Mikro Und Informationstechnik | Welsche M.,Albert Ludwigs University of Freiburg | And 4 more authors.
Journal of Micromechanics and Microengineering | Year: 2011

We investigate TMMF photopolymer as a cost-efficient alternative to glass for the leak-tight sealing of high-density silicon microchannels. TMMF enables low temperature sealing and access to structures underneath via lamination and standard UV-lithography instead of costly glass machining and anodic bonding. TMMF is highly transparent and has a low autofluorescence for wavelengths larger than 400 nm. As the photopolymer is too thin for implementing bulky world-to-chip interfaces, we propose adhesive bonding of cyclic olefin copolymer (COC) modules. All materials were tested according ISO 10993-5 and showed no cytotoxic effects on the proliferation of L929 cells. To quantify the cost efficiency of the proposed techniques, we used an established silicon/Pyrex nanoliter dispenser as a reference and replaced structured Pyrex wafers by TMMF laminates and COC modules. Thus, consumable costs, manpower and machine time related to sealing of the microchannels and implementing the world-to-chip interface could be significantly reduced. Leak tightness was proved by applying a pressure of 0.2 MPa for 5 h without delamination or crosstalk between neighboring microchannels located only 100 μm apart. In contrast to anodic bonding, the proposed techniques are tolerant to surface inhomogeneities. They enable manufacturing of silicon/polymer microfluidics at lower costs and without compromising the performance compared to corresponding silicon/glass devices. © 2011 IOP Publishing Ltd.


Peters C.,Albert Ludwigs University of Freiburg | Handwerker J.,Albert Ludwigs University of Freiburg | Maurath D.,Albert Ludwigs University of Freiburg | Maurath D.,Institute For Mikro Und Informationstechnik | And 2 more authors.
ISCAS 2010 - 2010 IEEE International Symposium on Circuits and Systems: Nano-Bio Circuit Fabrics and Systems | Year: 2010

This paper presents an ultra-low-voltage active rectifier for micro energy harvesting. A two stage concept is used including a first passive stage and an active diode as second stage. A bulk-input comparator design is used which is well suited for low voltage applications. The power consumption is 200 nW and the minimum operation voltage is 350 mV using a 0.35 μm low VTh CMOS technology. The voltage drop over the rectifier is some tens of millivolt which results in voltage and power efficiencies of over 90 %. Input voltages with frequencies in the range of mHz to low kHz can be rectified. ©2010 IEEE.


Trebbels D.,Institute For Mikro Und Informationstechnik | Woelki D.,Institute For Mikro Und Informationstechnik | Zengerle R.,Institute For Mikro Und Informationstechnik
Journal of Physics: Conference Series | Year: 2010

This paper presents a new approach for high precision phase measurement. The new system is developed for biomedical applications such as complex cell impedance measurement and dielectric tissue analysis. In many of the named applications it is necessary to measure the complex dielectric constant of a sample as a function of frequency. Therefore the developed system is capable of measuring amplitude and especially high precision phase of the measurement signal over a wide frequency range from 10 Hz to 10 MHz. The experimental result of the new method shows a phase resolution of up to 0.01 degree at 1 MHz and 0.1 degree at 10 MHz. The excellent phase measurement resolution is achieved by a time transformation of the signal using a digital sampling circuitry. The functional principle of the digital sampling circuitry is based on Delta-Modulation and is implemented inside a cheap standard FPGA. The new system is successfully used in blood analysis applications and allows for a practical implementation of cost efficient capacitive hematocrit sensors for the first time. © 2010 IOP Publishing Ltd.


Abbas Y.,Albert Ludwigs University of Freiburg | Abbas Y.,University of Twente | Miwa J.,Albert Ludwigs University of Freiburg | Zengerle R.,Albert Ludwigs University of Freiburg | And 3 more authors.
Micromachines | Year: 2013

We present a continuous-flow active micromixer based on channel-wall deflection in a polydimethylsiloxane (PDMS) chip for volume flows in the range up to 2 μL s-1 which is intended as a novel unit operation for the microfluidic Braille pin actuated platform. The chip design comprises a main microchannel connected to a series of side channels with dead ends aligned on the Braille pins. Computer-controlled deflection of the side-channel walls induces chaotic advection in the main-channel, which substantially accelerates mixing in low-Reynolds number flow. Sufficient mixing (mixing index MI below 0.1) of volume flows up to 0.5 μL s-1 could be achieved within residence times ~500 ms in the micromixer. As an application, continuous dilution of a yeast cell sample by a ratio down to 1:10 was successfully demonstrated. The mixer is intended to serve as a component of bio-analytical devices or as a unit operation in the microfluidic Braille pin actuated platform.


Cupelli C.,Albert Ludwigs University of Freiburg | Borchardt T.,Albert Ludwigs University of Freiburg | Steiner T.,Albert Ludwigs University of Freiburg | Paust N.,Institute For Mikro Und Informationstechnik | And 4 more authors.
Microfluidics and Nanofluidics | Year: 2013

In this paper, a simple and robust design for a passive hydrodynamic cell sorter based on pinched flow-field fractionation is presented and analyzed. Two principal layouts of the sorter are discussed and investigated experimentally as well as numerically based on the dissipative particle dynamics (DPD) method. Experimentally, design 1 approximately sorts 87 % of the erythrocytes to their designated outlet, while 100 % of the leukocytes branch correctly. This also holds for design 2 differing merely in the direction of the outlet for erythrocytes, but here only 69 % of the red blood cells are redirected to the designated outlet. This behavior can be elucidated by employing DPD simulations, where erythrocytes advected with the flow are modeled explicitly. Our results suggest that if a cell sorter is designed to operate at high throughput, its layout may not entirely rely on commonly assumed idealizing conditions, because cells cannot be considered as point-like, isolated objects following definite stream lines. Hydrodynamic forces originating from the cells as extended objects must be taken into account. © 2012 Springer-Verlag Berlin Heidelberg.


Zehnle S.,Institute For Mikro Und Informationstechnik | Schwemmer F.,Albert Ludwigs University of Freiburg | Roth G.,Institute For Mikro Und Informationstechnik | Roth G.,Albert Ludwigs University of Freiburg | And 5 more authors.
Lab on a Chip - Miniaturisation for Chemistry and Biology | Year: 2012

We present a method to pump liquids in a centrifugal microfluidic spinning disk from a radial outward position to a radial inward position. Centrifugal forces are applied to compress air in a cavity, this way storing pneumatic energy. The cavity is connected to an outlet channel having a lower hydraulic resistance compared to the inlet channel. The stored pneumatic energy is quickly released by fast reduction of rotational frequency. This way liquid is transported mainly through the channel with lower resistance, directing the liquid radially inwards. Pump efficiencies of >75% per pump cycle have been demonstrated for water, ethanol, a highly viscous lysis buffer and whole blood. By employing three pump cycles, water has been pumped radially inwards with an efficiency of >90%. The inward pumping requires centrifugation only, which is intrinsically available on every centrifugal microfluidic platform. © 2012 The Royal Society of Chemistry.

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