Biomedical subjects

Martin Heule

Publications and source records attributed to Martin Heule.

3 recordsLinked to original sources

PubMed2006

On-chip extrusion of lipid vesicles and tubes through microsized apertures.

In this work we present the formation of micrometre-sized lipid vesicles and tubes with perfectly homogeneous diameter and extraordinary length. The method is a novel approach for unconventional fabrication of soft-matter microstructured devices based on the combination of top-down and bottom-up fabrication processes. Photolithography techniques are applied to fabricate microsized apertures that provide the requirements to form lipid structures with predictable size and to align and guide the vesicles and tubes in microstructured channels. The formation is facilitated by self-assembly of polar lipids to a lipid membrane that is afterwards forced to undergo a shape transformation by extrusion through a microsized aperture. Both the geometrical restriction by the small aperture and the pressure difference between the top and bottom sides of the aperture determine the form and length of the vesicles and tubes. A strong pressure difference favors the formation of lipid tubes, while a low pressure difference results in the formation of vesicle bunches with spherical and cylindrical shapes. Potential applications for the formed lipid structures could be as microreactors and transport channels as well as in the construction of flexible microfluidic networks.

Dimethylpolysiloxanes↗

PubMed2005

Gentle cell trapping and release on a microfluidic chip by in situ alginate hydrogel formation.

Microfluidic devices are increasingly used to perform biological experiments on a single-cell basis. However, long-term stability of cell positions is still an issue. A novel biocompatible method for cell entrapment and release on a microchip is presented. It is based on the controlled formation of an alginate hydrogel by bringing two laminar flows of alginate and calcium ions in the range of 2 mM to 40 mM into contact. The resulting growth of a gel bar is used to enclose and immobilize yeast cells. Adding ethylenediaminetetraacetic acid (EDTA) to the alginate solution allows for control of the hydrogel growth, and by varying the ratio of Ca(2+) to EDTA concentrations gel growth or gel shrinkage can be induced at will. Trapped cells are released during shrinkage of the gel. The trapping efficiency for different cell speeds is investigated and the properties of gel growth are discussed using a diffusion model. Precise positioning of a single cell is demonstrated. The technique presented allows not only the reversible immobilization of cells under gentle conditions but also offers the potential of long-term cell cultures as shown by on-chip incubation of yeast cells. The procedure may provide a simple and fully biocompatible technique for a multitude of innovative experiments on cells in microsystems.

Alginates↗

PubMed2004

Sequential DNA hybridisation assays by fast micromixing.

The prospects of performing DNA hybridisation assays in a novel sequential scheme are explored in this article. It is based on recording the kinetics of hybridisation on a microfluidic device measuring only 10 by 5 mm. It contains a split channel system for fast mixing and a subsequent meandering channel to observe the evolution of the mixture by optical means. The problems of diffusion limitations in the laminar flow regime are overcome by reducing the average diffusion distance to a few micrometers only. DNA oligomers (20-mers) of different sequences were injected on the chip for mixing. The detection of hybridisation was based on the fluorescence of DNA-intercalating dyes. Two modes of operation were investigated. First, the samples were injected into the micromixing device at a high flow rate of 40 microl min(-1). When the sample passed through the actual micromixing unit, the flow rate was reduced to allow for measurement of fluorescence levels at various steady-state reaction times in the range of 2-15 s, as defined by the channel geometry. Using this continuous flow approach, photobleaching of fluorophores could be avoided. In a buffer containing 0.2 M NaCl, 2 base-pair mismatches could routinely be detected within 5-20 s. Single base-pair mismatches were successfully identified under low salt conditions. In the second mode, the flow was completely stopped and the evolution of the total fluorescence signal influenced by the hybridisation of oligomers and photobleaching was observed. Whereas the sequence-dependent effects remained unchanged, the assay times between the mixing of two oligomers and clear identification of their hybridisation properties could be reduced down to a maximum of 5-7 s, in some cases even below 1 s.

DNA↗