Publications by authors named "Michael Vellekoop"

Silica aerogels are highly porous materials with unique properties such as high specific surface area, high thermal insulation, and high open porosity. These characteristics make them attractive for several applications in closed microfluidic channels such as BioMEMS, catalysis, and thermal insulation. However, aerogel-filled microchannels have not been reported in the literature yet because of the complexity of creating a process that controls the integration, shrinkage, and mechanical stability of these materials inside a closed channel.

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In this work, we present a microsystem setup for performing sensitive biological membrane translocation measurements. Thin free-standing synthetic bilayer lipid membranes (BLM) were constructed in microfabricated silicon nitride apertures (<100 µm in diameter), conformal coated with Parylene (Parylene-C or Parylene-AF4). Within these BLMs, electrophysiological measurements were conducted to monitor the behavior of different pore proteins.

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We present a chip design allowing rapid and robust lipid bilayer (LBL) membrane formation using a Parylene coated thin silicon nitride aperture. After bilayer formation, single membrane channels can be reconstituted and characterized by electrophysiology. The ability for robust reconstitution will allow parallelization and enhanced screening of small molecule drugs acting on or permeating across the membrane channel.

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The capture of circulating tumor cells (CTCs) is still a challenging application for microfluidic chips, as these cells are rare and hidden in a huge background of blood cells. Here, different microfluidic ceiling designs in regard to their capture efficiency for CTCs in model experiments and more realistic conditions of blood samples spiked with a clinically relevant amount of tumor cells are evaluated. An optimized design for the capture platform that allows highly efficient recovery of CTCs from size-based pre-enriched samples under realistic conditions is obtained.

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We present a miniature 3D-printed dynamic pump using the centrifugal operating principle. Dynamic pumps typically yield higher flow rates than displacement pumps at reasonable output pressure. Realizing smaller devices suitable for millifluidic and microfluidic applications brings challenges in terms of design, fabrication and actuation.

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Optimized culture conditions are essential for the investigation of biological processes. In this work, on-chip optimization of bacterial culture conditions by combining microfluidics with the Box-Behnken design response surface methodology is presented. With this methodology, the effects of several cultivation variables and their interactions were investigated enabling very fast drug susceptibility screening.

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Microfluidic cell cultures are often used in academic research but only rarely in pharmaceutical research because of unsuitable designs, inappropriate choice of materials or incompatibility with standard equipment. In particular, microfluidic cell cultures to control the gaseous microenvironment rely on PDMS despite its disadvantages. We present a novel concept for such a cell culture device that addresses these issues and is made out of hard materials instead of PDMS.

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The connection of microfluidic devices to the outer world by tubes and wires is an underestimated issue. We present methods based on 3D printing to realize microfluidic chip holders with reliable fluidic and electric connections. The chip holders are constructed by microstereolithography, an additive manufacturing technique with sub-millimeter resolution.

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Fungus is enormously notorious for food, human health, and archives. Fungus sign and symptoms in medical science are non-specific and asymmetrical for extremely large areas resulting into a challenging task of fungal detection. Various traditional and computer vision techniques were applied to meet the challenge of early fungus detection.

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Ethylene gas is a naturally occurring gas that has an influence on the shelf life of fruit during their transportation in cargo ships. An unintentional exposure of ethylene gas during transportation results in a loss of fruit. A gas chromatographic system is presented here for the detection of ethylene gas.

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Lab-on-a-Chip (LoC) applications for the long-term analysis of mammalian cells are still very rare due to the lack of convenient cell cultivation devices. The difficulties are the integration of suitable supply structures, the need of expensive equipment like an incubator and sophisticated pumps as well as the choice of material. The presented device is made out of hard, but non-cytotoxic materials (silicon and glass) and contains two vertical arranged membranes out of hydrogel.

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An infrared (IR) absorbance sensor has been designed, realized and tested with the aim of detecting malignant melanomas in human skin biopsies. The sensor has been designed to obtain fast measurements (80 s) of a biopsy using a small light spot (0.5 mm in diameter, typically five to 10 times smaller than the biopsy size) to investigate different biopsy areas.

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A new miniaturized sensor system with an internal optical reference for the detection of mold growth is presented. The sensor chip comprises a reaction chamber provided with a culture medium that promotes the growth of mold species from mold spores. The mold detection is performed by measuring impedance changes with integrated electrodes fabricated inside the reaction chamber.

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Phononic crystals offer unique band structures for acoustic wave propagation. Fabricating intricate threedimensional phononic crystals allows a new class of devices with complex phononic band structures beyond capabilities of two-dimensional designs. We have successfully fabricated novel 3D phononic crystals with 1 mm lattice constant and minimum feature sizes as low as 100 micron using high-resolution stereolithography printing.

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We present a compact diagnostic platform for a rapid and sensitive detection of plasma biomarkers. The platform consists of a disposable microfluidic polymer chip, a processing device including a lens-free and cost efficient sensor system and a setup for dispersion of magnetic particles. The biomarkers of interest are quantified by magnetic bead based immunoassays with chemiluminescent readout technology.

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Analyses of rare events occurring at extremely low frequencies in body fluids are still challenging. We established a versatile microarray-based platform able to capture single target cells from large background populations. As use case we chose the challenging application of detecting circulating tumor cells (CTCs)--about one cell in a billion normal blood cells.

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This work presents an array of microfluidic chambers for on-chip culturing of microorganisms in static and continuous shear-free operation modes. The unique design comprises an in-situ polymerized hydrogel that forms gas and reagent permeable culture wells in a glass chip. Utilizing a hydrophilic substrate increases usability by autonomous capillary priming.

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We present Brownian motion-based sizing of individual submicron and nanoparticles in liquid samples. The advantage of our approach is that particles can freely diffuse in a 10 μm thin liquid film and are therefore always within the focal depth of a low numerical aperture objective. Particles are visualized with dark-field microscopy, and the resulting diffraction-limited spots are tracked over a wide field of view of several hundred micrometers.

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For the first time we demonstrate a microfluidic platform for the preparation of biosensing hydrogels by in situ polymerization of polyethyleneglycol diacrylate (PEG-DA) in a single step. Capillary pressure barriers enable the precise formation of gel microstructures for fast molecule diffusion. Parallel arrangement of these finger structures allows for macroscopic and standard equipment readout methods.

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We present a fully automated setup for performing in-line mass spectrometry (MS) analysis of conditioned media in cell cultures, in particular focusing on the peptides therein. The goal is to assess peptides secreted by cells in different culture conditions. The developed system is compatible with MS as analytical technique, as this is one of the most powerful analysis methods for peptide detection and identification.

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We present a novel optofluidic device for non-invasive and label-free determination of liquid concentrations. A microfluidic channel filled with the sample solution is hit by laser light in an angle close to the critical angle for total internal reflection. Due to the intentionally defined divergence of the incident beam, parts of the rays will experience total internal reflection while another part will be transmitted.

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In this study, the pre-steady state development of enzymatic bioreactions using a microfluidic mixer is presented. To follow such reactions fast mixing of reagents (enzyme and substrate) is crucial. By using a highly efficient passive micromixer based on multilaminar flow, mixing times in the low millisecond range are reached.

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In this work, a novel optofluidic sensor principle is employed for a non-invasive and label-free characterization of lactose containing liquid samples. Especially for medicine and food industry, a simple, fast and accurate determination of the amount of lactose in various products is highly desirable. The presented system exploits the impact of dissolved molecules on the refractive index for sample characterization.

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In this paper, we assess the potential of a label-free infrared absorbance based measurement method for determination of the CH(2)-symmetric to CH(2)-antisymmetric stretch ratio, to aid in the detection of the presence of cancer cells and to differentiate between various cancer cells. For this study a normal epithelial kidney cell line, two carcinoma epithelial kidney cell lines, an adult primary human melanocyte cell line, and three human melanoma cell lines were investigated. For the measurements we used a self-designed IR sensor which has the potential to be further developed in a point-of-care instrument.

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A specially designed micro-mixer made of silicon, calcium fluoride, and silicone with an optical transmission path of 8 μm has been used for mid-IR spectroscopy monitoring of mixing-induced chemical reactions in the low millisecond time regime. The basic principle of the proposed continuous-flow technique is to mix two liquids introduced in two times two alternatingly stacked layers through diffusion at the entrance of a 200 μm wide, 1 cm long micro-fluidic channel also serving as measurement area. By using this special, dedicated arrangement, diffusion lengths and hence the mixing times can be significantly shortened and the overall performance improved in comparison to previous systems and alternative methods.

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