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Biomedical subjects

Andreas Manz

Publications and source records attributed to Andreas Manz.

At least 19 recordsLinked to original sources
PubMed2006

Scaling and the design of miniaturized chemical-analysis systems.

Micrometre-scale analytical devices are more attractive than their macroscale counterparts for various reasons. For example, they use smaller volumes of reagents and are therefore cheaper, quicker and less hazardous to use, and more environmentally appealing. Scaling laws compare the relative performance of a system as the dimensions of the system change, and can predict the operational success of miniaturized chemical separation, reaction and detection devices before they are fabricated. Some devices designed using basic principles of scaling are now commercially available, and opportunities for miniaturizing new and challenging analytical systems continue to arise.

Animals↗
PubMed2006

Construction and analytical application of an on-column photo reactor for improved detection of iron-species as plant metabolites in capillary flow injection and capillary electrophoresis.

An on-column photo reactor for CE, which is constructed from UV-transparent capillaries and a small Pen-Ray UV lamp, is applied to the analysis of small, non-covalent iron-species. These iron-species, e.g. phytosiderophores (PS) in grasses and the non-protein amino acid nicotianamine (NA), play an important role in plant metabolism. The photo reactor is placed directly in front of the on-column absorbance detector, illuminating only some centimeters of the capillary. The photo reactor is used for capillary electrophoresis (CE) and also for capillary flow injection analysis (CFIA). Photoinduced sensitivity changes for model iron-species and for plant extracts are investigated, using UV detection and capacitively coupled contactless conductivity detection (C(4)D). The detection sensitivity for iron-species is enhanced in CFIA; the enhancement factor depends on the type of iron-species. In CE, the sensitivity of iron-species is kinetically dependent on the type of iron-species, decreasing with both detectors, but a photo reaction product is detectable. The relationship between irradiation window length and sensitivity is investigated quantitatively using EDTA-Fe(III). Pure ligands without iron are little affected by the photo reaction in both CFIA and CE. In CE, the detector signals of iron-species in real plant samples are selectively decreased with the proposed photo reactor, thus enabling a simple screening method for such photoactive iron-species.

Electrophoresis, Capillary↗
PubMed2006

Isotachophoresis in free-flow using a miniaturized device.

For the first time, we report a miniaturized approach for isotachophoresis employing the technique of free-flow electrophoresis. Using a micromachined separation chamber with a volume of 200 nL, a sample mixture of fluorescein, eosin G, and acetylsalicylic acid was separated, stacked, and concentrated in less than a minute. Additionally, an isotachophoretic separation of a reaction mixture of myoglobin and fluoresceinisothiocyanate as a fluorescence label has shown the potential of this method for on-line sample preparation.

Journal Article↗
PubMed2006

Miniaturised isotachophoresis analysis.

The application of miniaturized total analysis systems (microTAS) has seen rapid development over the past few years. Isotachophoresis (ITP) has been transferred into microchip format for both electrophoretic separation and pretreatment purposes, due to its advantageous features including separation parameters controlled by electrolyte composition and high sample load capacity. The primary focus of this concise review is to summarize the basic features of microchip based ITP and its applications to the analysis and pretreatment of ionic compounds and biomolecules that have arisen since 1998.

DNA↗
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↗
PubMed2006

Lab-on-a-chip: microfluidics in drug discovery.

Miniaturization can expand the capability of existing bioassays, separation technologies and chemical synthesis techniques. Although a reduction in size to the micrometre scale will usually not change the nature of molecular reactions, laws of scale for surface per volume, molecular diffusion and heat transport enable dramatic increases in throughput. Besides the many microwell-plate- or bead-based methods, microfluidic chips have been widely used to provide small volumes and fluid connections and could eventually outperform conventionally used robotic fluid handling. Moreover, completely novel applications without a macroscopic equivalent have recently been developed. This article reviews current and future applications of microfluidics and highlights the potential of 'lab-on-a-chip' technology for drug discovery.

Drug Design↗
PubMed2005

Shear-driven pumping and Fourier transform detection for on chip circular chromatography applications.

A circular, shear-driven pumping system combined with Fourier Transform detection has been developed for the application of chip based cyclic chromatography. Using this system, it is possible to perform an injection of a sample plug into a circular micro-channel and then drive the sample through the channel, using shear flow induced by a rotation stage. High pumping rates at uniform speeds are attainable with this system with very little heat production. Typical pumping rates of up to 1.423 mm s(-1) +/- 2 microm s(-1) were used in experiments although much higher rates >14 mm s(-1) are also possible with this system. Fluorescence detection was used to detect a sample plug of Coumarin dyes, flowing around the channel. A coating of porous polymethacrylate was used to immobilise RP-HPLC beads onto the glass surface and was applied to the glass micro-channel by selective photopolymerisation. This coating acted as a stationary phase and differences in retention time were observed for an injection of Coumarin dyes for different methanol-water, mobile phase ratios. Full sample retention occurred for 30 : 70 (v/v) methanol-water whereas no retention occurred for 92 : 8 (v/v) methanol-water which can be expected for such a reverse phase, open tubular system. Fourier transform detection applied to the fully retained and non-retained cases showed frequency domain data from a single detection point corresponding to that which may be expected from shear flow theory.

Journal Article↗
PubMed2005

Single-molecule fluorescence detection in microfluidic channels--the Holy Grail in muTAS?

Both single-molecule detection (SMD) methods and miniaturization technologies have developed very rapidly over the last ten years. By merging these two techniques, it may be possible to achieve the optimal requirements for the analysis and manipulation of samples on a single molecule scale. While miniaturized structures and channels provide the interface required to handle small particles and molecules, SMD permits the discovery, localization, counting and identification of compounds. Widespread applications, across various bioscience/analytical science fields, such as DNA-analysis, cytometry and drug screening, are envisaged. In this review, the unique benefits of single fluorescent molecule detection in microfluidic channels are presented. Recent and possible future applications are discussed.

Biosensing Techniques↗
PubMed2005

Direct optical emission spectroscopy of liquid analytes using an electrolyte as a cathode discharge source (ELCAD) integrated on a micro-fluidic chip.

Atomic emission detection of metallic species in aqueous solutions has been performed using a miniaturised plasma created within a planar, glass micro-fluidic chip. Detection was achieved using an Electrolyte as a Cathode Discharge source (ELCAD) in which the sample solution itself is used as the cathode for the discharge. To realise the ELCAD technique within a micro-fluidic device, a parallel liquid-gas flow was set up in a micro-channel and a glow discharge ignited between the flowing liquid sample surface and a metal wire anode. The detection of copper and sodium was achieved, using atmospheric pressure air as a carrier gas, by observation of atomic emission lines of copper at 324 nm, 327 nm, 511 nm, 515 nm and 522 nm and an atomic emission line of sodium at 589 nm using a commercially available miniaturised spectrometer. A total electrical power of less than 70 mW was required to sustain the discharge. A semi-quantitative, absolute detection limit of 17 nmol s(-1) was obtained for sodium with a sample flow rate of 100 microL min(-1) and an integration time of 100 ms in air at atmospheric pressure. The volume required for such detection is approximately 170 nL. Further analysis was performed with an Echelle spectrometer using both argon and air as a carrier gas. The geometry and flow rates used demonstrate the feasibility of integrating such micro-plasmas into other micro-fluidic devices, such as miniaturised CE devices, as a method of detection. The potential for using such micro-plasmas within highly portable miniaturised systems and mu-TAS devices is presented and discussed.

Journal Article↗
PubMed2005

Laser induced disruption of bacterial spores on a microchip.

We report on the development of a laser based spore disruption method. Bacillus globigii spores were mixed with a laser light absorbing matrix and co-crystallized into 200-microm-wide and 20-microm-deep nanovials formed in a polydimethylsiloxane (PDMS) target plate. Surface tension effects were exploited to effect up to 125-fold spore enrichment. When the target zones were illuminated at atmospheric pressure with pulsed UV-laser light at fluences below 20 mJ cm(-2) a change in spore morphology was observed within seconds. Post illumination PCR analysis suggests the release of endogenous DNA indicative of spore disruption. For laser fluences above 20 mJ cm(-2), desorption of spores and fragments was also observed even without a matrix being employed. Desorbed material was collected in a PDMS flowcell attached to the target plate during laser illumination. This opens up a route towards the direct extraction of released DNA in an integrated spore disruption-PCR amplification microchip device.

Bacillus↗
PubMed2005

Toward on-chip X-ray analysis.

The possibility of performing chemical analysis and structure determinations with the use of X-rays in a microfluidic chip environment is explored. Externally generated radiation, radioisotope irradiation and on-chip generated X-rays were considered as excitation means for the performance of sample analysis with the techniques of X-ray fluorescence and diffraction. The absorption properties of chip-building materials by different radiation sources are reviewed and data on absorption coefficients calculated, upon which recommendations for optimisations with the use of various X-ray sources may be made. The capabilities and limitations of on-chip X-ray analysis are placed in perspective by preliminary experimental results of diffraction, fluorescence and on-chip X-ray generation experiments.

Absorption↗
PubMed2004

Dry powder injection on chip.

To match the current speed of drug development there is a serious requirement for the pharmaceutical industry to upgrade powder handling processes. Miniaturization is a key concept especially in the early stages of drug development when only small amounts of the drug compound are available. This paper shows for the first time the application of miniaturization through chip technology for dry powder handling. Two methods to separate and transport minute amounts of dry powder particles on chip are described. Both techniques could be employed in small scale mixing devices, which depend on reliable particle feeding systems to substitute balances and the time consuming weighing process.

Biosensing Techniques↗
PubMed2004

On-chip free-flow magnetophoresis: continuous flow separation of magnetic particles and agglomerates.

The separation of magnetic microparticles was achieved by on-chip free-flow magnetophoresis. In continuous flow, magnetic particles were deflected from the direction of laminar flow by a perpendicular magnetic field depending on their magnetic susceptibility and size and on the flow rate. Magnetic particles could thus be separated from each other and from nonmagnetic materials. Magnetic and nonmagnetic particles were introduced into a microfluidic separation chamber, and their deflection was studied under the microscope. The magnetic particles were 2.0 and 4.5 microm in diameter with magnetic susceptibilities of 1.12 x 10(-4) and 1.6 x 10(-4) m(3) kg(-1), respectively. The 4.5-microm particles with the larger susceptibility were deflected further from the direction of laminar flow than the 2.0-microm magnetic particles. Nonmagnetic 6-microm polystyrene beads, however, were not deflected at all. Furthermore, agglomerates of magnetic particles were found to be deflected to a larger extent than single magnetic particles. The applied flow rate and the strength and gradient of the applied magnetic field were the key parameters in controlling the deflection. This separation method has a wide applicability since magnetic particles are commonly used in bioanalysis as a solid support material for antigens, antibodies, DNA, and even cells. Free-flow magnetophoretic separations could be hyphenated with other microfluidic devices for reaction and analysis steps to form a micro total analysis system.

Antibodies↗
PubMed2004

A double plasma gas chromatography injector and detector.

A direct-current, chip-based plasma has been used for gas sample injection in gas chromatography. A second identical plasma chip has been used as the excitation source for an optical emission detector. The first plasma is normally continually sustained during operation, causing continuous ionisation/fragmentation of the sample, whilst the second plasma records the optical emission downstream. For injection, the first plasma is briefly interrupted, introducing a "plug" of unmodified sample into the system. Injection plug sizes of between 5 and 50 [micro sign]l have been reproducibly obtained, although significantly smaller volumes may be possible with the use of smaller cross-section columns, lower flow rates and/or shorter plasma interruption times.

Chemical Phenomena↗
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↗