Martin A. M. Gijs

Microfluidic applications of magnetic particles for biological analysis and catalysis

Keywords: Spin-Valve Sensors ; Cell Tracking Velocimetry ; On-A-Chip ; Polymerase-Chain-Reaction ; Total Analysis Systems ; Iron-Oxide Nanoparticles ; Field-Flow Fractionation ; Cross-Coupling Reactions ; Circulating Tumor-Cells ; Mode Magnetophoretic Microseparator Reference LMIS2-ARTICLE-2010-004doi:10.1021/cr9001929View record in Web of Science Record created on 2010-01-20, modified on 2016-08-08

Long-range transport of magnetic microbeads using simple planar coils placed in a uniform magnetostatic field

We propose an approach for magnetic microbead transport in microfluidic channels over long-range distances using an array of simple planar coils. The latter are placed in a uniform static magnetic field, the role of which is to impose a permanent magnetic moment to the microbeads. The very small magnetic field gradient of a simple planar coil is then sufficient to displace the microbeads. The long-range displacement is assured by arranging adjacent coils in the array with spatial overlap in a three-phase actuation scheme.

Miniaturized Flexible Temperature Sensor

We propose a microfabrication technology for a flexible temperature sensor with a 100times100 mum sensing area and a probe length of 7 cm. We use a biocompatible new high temperature-resistant polyimide (U-Varnish-S, Ube, Diisseldorf, Germany) to embed a thin film platinum resistor as sensing element. The sensor is operational from 0degC up to 400degC with an accuracy of plusmn1degC at high temperatures and has a time constant of 0.05 seconds. This sensor was designed for temperature characterisation of hot steam injected for thermo-ablation of tumours via a micro-needle.

Plastic micropump with ferrofluidic actuation

We present the realization and characterization of a new type of plastic micropump based on the magnetic actuation of a magnetic liquid. The pump consists of two serial check-valves that convert the periodic motion of a ferrofluidic plug into a pulsed quasi-continuous flow. The ferrofluid is actuated by the mechanical motion of an external NdFeB permanent magnet. The water-based ferrofluid is synthesized in-house using a coprecipitation method and has a saturation magnetization of 32 mT. The micropump consists of various layers of polymethylmethacrylate (PMMA), which are microstructured by powder blasting or by standard mechanical micromachining techniques, and are assembled in a single plastic structure using a monomer gluing solution. Two soft silicone membranes are integrated in the microfluidic structure to form two check-valves. Water has been successfully pumped at flow rates of up to 30 /spl mu/L/min and pumping is achieved at backpressures of up to 25 mbar.

Defect structure in micropillars using X-ray microdiffraction

White beam x-ray microdiffraction is used to investigate the microstructure of micron-sized Si, Au, and Al pillars fabricated by focused ion beam (FIB) machining. Comparison with a Laue pattern obtained from a Si pillar made by reactive ion etching reveals that the FIB damages the Si structure. The Laue reflections obtained from the metallic pillars fabricated by FIB show continuous and discontinuous streakings, demonstrating the presence of strain gradients.

Validation of an In Vitro Digestive System for Studying Macronutrient Decomposition in Humans

The digestive process transforms nutrients and bioactive compounds contained in food to physiologically active compounds. In vitro digestion systems have proven to be powerful tools for understanding and monitoring the complex transformation processes that take place during digestion. Moreover, the investigation of the physiological effects of certain nutrients demands an in vitro digestive process that is close to human physiology. In this study, human digestion was simulated with a 3-step in vitro process that was validated in depth by choosing pasteurized milk as an example of a complex food matrix. The evolution and decomposition of the macronutrients was followed over the entire digestive process to the level of intestinal enterocyte action, using protein and peptide analysis by SDS-PAGE, reversed-phase HPLC, size exclusion HPLC, and liquid chromatography-MS. The mean peptide size after in vitro digestion of pasteurized milk was 5-6 amino acids (AA). Interestingly, mostly essential AA (93.6%) were released during in vitro milk digestion, a significantly different relative distribution compared to the total essential AA concentration of bovine milk (44.5%). All TG were degraded to FFA and monoacylglycerols. Herein, we present a human in vitro digestion model validated for its ability to degrade the macronutrients of dairy products comparable to physiological ranges. It is suited to be used in combination with a human intestinal cell culture system, allowing ex vivo bioavailability measurements and assessment of the bioactive properties of food components.

On-chip immuno-agglutination assay with analyte capture by dynamic manipulation of superparamagnetic beads

Magnetic bead-based lab-on-a-chip systems offer significant advantages compared to more conventional systems, mainly through the possibility of controlled manipulation of the magnetic carriers on-chip. In particular, microfluidic immunoassays using functionalized magnetic beads raise increasing interest. We present here a new approach for performing immuno-agglutination assays on-chip. Our system is based on a quadrupolar magnetic field set-up. Dynamic actuation of a confined plug of functionalized magnetic beads is used for analyte capture in a microchannel. A simple detection method based on the swelling of the released plug after agglutination is presented. We demonstrate the feasibility of on-chip agglutination tests by means of a streptavidin/biotinylated-bovine serum albumin (bBSA) model assay. A detection limit of about 200 pg/mL (approximately 3 pM) is achieved.

Full On-Chip Nanoliter Immunoassay by Geometrical Magnetic Trapping of Nanoparticle Chains

We propose an original concept to perform a complete on-chip sandwich immunoassay on magnetic nanoparticles that are self-assembled in chains in a uniform magnetic field. The magnetic chains are retained over periodically enlarged cross sections of a microfluidic channel. Thereby they strongly interact with the flow and rapidly capture the total of a low number of target molecules from nanoliter sample volumes. As an example, we demonstrate the detection of murine monoclonal antibodies in a noncompetitive sandwich immunoassay with a detection limit of 1 ng mL(-1) in nanoliters of hybridoma cell culture medium.

Realization of hollow SiO2 micronozzles for electrical measurements on living cells

We present a microfluidic device for the immobilization and electrical measurements, such as patch-clamp or impedance measurements, on individual living cells. Micron-sized hollow SiO2 nozzles are realized in Si wafers using a deep plasma etching process. The micronozzles are integrated with glass wafers containing microfluidic channels and Ag/AgCl electrodes. Reliable cell positioning on the nozzles via hydrodynamic forces is obtained. Relevant electrical parameters of the system, especially seal resistances between attached cells and the nozzle, are determined.

Micromachining of glass inertial sensors

We demonstrate the feasibility of a powder blasting micro-erosion process for the micromachining of accelerometer devices in glass. Using high-speed abrasive microparticles and a metal contact mask, we structure millimeter-size cantilever beams from simple glass slides. By metalizing one side of the glass substrate, we demonstrate both capacitive and piezoresistive/strain gauge detection of the vibrating cantilever mass and measure the frequency response of mechanically excited cantilever beams. We think that our approach opens new perspectives for manufacture of inertial sensing devices in a technology alternative to Si.