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N F de Rooij

Publications and source records attributed to N F de Rooij.

15 recordsLinked to original sources
PubMed2003

Planar microcoil-based microfluidic NMR probes.

Microfabricated small-volume NMR probes consisting of electroplated planar microcoils integrated on a glass substrate with etched microfluidic channels are fabricated and tested. 1H NMR spectra are acquired at 300 MHz with three different probes having observed sample volumes of respectively 30, 120, and 470 nL. The achieved sensitivity enables acquisition of an 1H spectrum of 160 microg sucrose in D2O, corresponding to a proof-of-concept for on-chip NMR spectroscopy. Increase of mass-sensitivity with coil diameter reduction is demonstrated experimentally for planar microcoils. Models that enable quantitative prediction of the signal-to-noise ratio and of the influence of microfluidic channel geometry on spectral resolution are presented and successfully compared to the experimental data. The main factor presently limiting sensitivity for high-resolution applications is identified as being probe-induced static magnetic field distortions. Finally, based on the presented model and measured data, future performance of planar microcoil-based microfluidic NMR probes is extrapolated and discussed.

Electronics↗
PubMed2001

Surface biopassivation of replicated poly(dimethylsiloxane) microfluidic channels and application to heterogeneous immunoreaction with on-chip fluorescence detection.

Poly(dimethylsiloxane) (PDMS) appeared recently as a material of choice for rapid and accurate replication of polymer-based microfluidic networks. However, due to its hydrophobicity, the surface strongly interacts with apolar analytes or species containing apolar domains, resulting in significant uncontrolled adsorption on channel walls. This contribution describes the application and characterization of a PDMS surface treatment that considerably decreases adsorption of low and high molecular mass substances to channel walls while maintaining a modest cathodic electroosmotic flow. Channels are modified with a three-layer biotin-neutravidin sandwich coating, made of biotinylated IgG, neutravidin, and biotinylated dextran. By replacing biotinylated dextran with any biotinylated reagent, the modified surface can be readily patterned with biochemical probes, such as antibodies. Combination of probe immobilization chemistry with low nonspecific binding enables affinity binding assays within channel networks. The example of an electrokinetic driven, heterogeneous immunoreaction for human IgG is described.

Dimethylpolysiloxanes↗
PubMed2001

Electrokinetically driven microfluidic chips with surface-modified chambers for heterogeneous immunoassays.

This article presents the first example of a microfluidic chip for heterogeneous bioassays using a locally immobilized biospecific layer and operated electrokinetically. The reaction chamber has picoliter dimensions and is integrated into a network of microchannels etched in glass. The high affinity of protein A (PA) for rabbit immunoglobulin G (rIgG) was exploited for chip testing, with PA being immobilized on microchannel walls and fluorescently labeled (Cy5) rIgG serving as sample. It was possible to operate the chip in an immunoaffinity chromatographic manner, using electrokinetically pumped solutions. Concentration of antibody from dilute solution onto the solid phase was demonstrated, with signal gains of approximately 30 possible. A dose-response curve for Cy5-rIgG was obtained for concentrations down to 50 nM, for an incubation time of 200 s. The flexibility of chip layout was demonstrated for competitive immunoassay of rIgG, using both a combined sample/tracer incubation and sequential addition of these solutions. With assay times generally below 5 min for this unoptimized device, the microfluidic approach described shows great potential for many high-throughput screening applications.

Carbocyanines↗
PubMed2001

Sample preconcentration by field amplification stacking for microchip-based capillary electrophoresis.

A microchip structure for field amplification stacking (FAS) was developed, which allowed the formation of comparatively long, volumetrically defined sample plugs with a minimal electrophoretic bias. Up to 20-fold signal gains were achieved by injection and separation of 400 microm long plugs in a 7.5 cm long channel. We studied fluidic effects arising when solutions with mismatched ionic strengths are electrokinetically handled on microchips. In particular, the generation of pressure-driven Poiseuille flow effects in the capillary system due to different electroosmotic flow velocities in adjacent solution zones could clearly be observed by video imaging. The formation of a sample plug, stacking of the analyte and subsequent release into the separation column showed that careful control of electric fields in the side channels of the injection element is essential. To further improve the signal gain, a new chip layout was developed for full-column stacking with subsequent sample matrix removal by polarity switching. The design features a coupled-column structure with separate stacking and capillary electrophoresis (CE) channels, showing signal enhancements of up to 65-fold for a 69 mm long stacking channel.

Adsorption↗
PubMed2001

Multi-layer microfluidic glass chips for microanalytical applications.

A new, versatile architecture is presented for microfluidic devices made entirely from glass, for use with reagents which would prove highly corrosive for silicon. Chips consist of three layers of glass wafers bonded together by fusion bonding. On the inside wafer faces a network of microfluidic channels is created by photolithography and wet chemical etching. Low dead-volume fluidic connections between the layers are fabricated by spark-assisted etching (SAE), a computer numerical controlled (CNC)-like machining technique new to microfluidic system fabrication. This method is also used to form a vertical, long path-length, optical cuvette through the middle wafer for optical absorbance detection of low-concentration compounds. Advantages of this technique compared with other, more standard, methods are discussed. When the new glass-based device for flow-injection analysis of ammonia was compared with our first-generation chips based on silicon micromachining, concentration sensitivity was higher, because of the longer path-length of the optical cuvette. The dependence of dispersion on velocity profile and on channel cross-sectional geometry is discussed. The rapid implementation of the devices for an organic synthesis reaction, the Wittig reaction, is also briefly described.

Journal Article↗
PubMed1997

Microelectrode arrays for electrophysiological monitoring of hippocampal organotypic slice cultures.

A three-dimensional platinum (Pt) microelectrode array embedded on a micromachined silicon (Si) substrate (porosity of 13%, via hole diameter of 40 microns) has been developed. Electrodes are 35-micron wide and 20-microns high, spaced 200 microns apart and arranged in an elliptic geometry. Integrated within a microperfusion chamber, the devices were used for stimulation and recording experiments of hippocampal slice cultures over a period of several days.

Animals↗
PubMed1994

Development of a miniature bioreactor for continuous culture in a space laboratory.

A new type of miniature bioreactor for continuous culture of yeast cells in space laboratories has been developed. Silicon microtechnology has permitted the integration of numerous functions and systems in a volume of 87 x 63 x 63 mm3 and a weight of 610 g. The 100 ml of fresh medium can be delivered at variable flow rates to the cultivation chamber (volume 3 ml) by means of a micropump. The culture is agitated by a magnetic stirrer. Microsensors monitor pH, temperature and redox potential. The decrease of pH occurring during the cultivation of Saccharomyces cerevisiae is compensated electrochemically. A window allows the inspection of the culture status. Samples of up to 1 ml can be drawn through a silicone rubber septum. The data measured by the sensors are transmitted on-line to the ground station during operations in space. The bioreactor had to fulfil several requirements related to the safety regulation of the space agencies. In particular, new materials had to be selected and tested for their biocompatibility. The instrument has now passed all space and biological qualification tests and will be used in an experiment selected by ESA for the International Microgravity Laboratory-2 Mission in Spacelab in July 1994. This paper gives the results of the functional and biological tests and a detailed description of the instrument.

Fermentation↗
PubMed1994

Glucose-sensitive enzyme field effect transistor using potassium ferricyanide as an oxidizing substrate.

A glucose-sensitive field effect transistor was fabricated by immobilizing glucose oxidase on the gate of a pH-sensitive field effect transistor. Calibration curves of the biosensor were measured in phosphate and TRIS buffers in the presence of potassium ferricyanide. The use of the latter as an oxidizing substrate in the biocatalytic oxidation of glucose leads to an increase of the acidification rate of the solution inside the enzymatic layer, because three protons are now generated per one molecule of glucose instead of only one when the natural oxidizing cosubstrate, oxygen, is used. Depending on the concentration of ferricyanide we observe a 10-100 times increase of the biosensor response in concentrated buffer solutions and a substantial extension of its dynamic range. At sufficiently high concentrations of ferricyanide, the calibration curves in both buffers have a sigmoidal shape in linear coordinates with local pH changes on the surface of the field effect transistor reaching about two pH units in the saturation range. The resulting saturation of the curves at higher glucose concentrations is due to the inhibition of the activity of glucose oxidase at acidic pH by Cl- ions present in the solution. The proposed approach may be extended to allow the detection of a wide range of analytes using enzyme field effect transistors based on the enzymes for which reoxidation of the cofactor (coenzyme) leads to a liberation of H+ ions.

Biosensing Techniques↗
PubMed1994

Micromachined analyzers on a silicon chip.

For an example of a silicon-based micromachined analyzer, we describe a combined PO2, PCO2, and pH sensor designed for extracorporeal blood gas monitoring. The clinically well-accepted amperometric (PO2) and potentiometric (PCO2, pH) sensing principles are used, realized in a planar and miniaturized form on a single silicon chip (6 x 22 mm). The transducer part of the chip is fabricated by standard silicon technology. Polyacrylamide and polysiloxane polymeric layers, which are used as internal electrolyte and gas-permeable membrane, respectively, are deposited and patterned by photopolymerization. The entire sensor is fabricated on the wafer level by using integrated-circuit-compatible processes, thus allowing mass production. By integrating a flow-through channel directly on the chip, the sample size and the reagent consumption are substantially reduced. The device was characterized in aqueous solutions and in blood intended for transfusion. The sensor has a typical sensitivity of 0.36 nA/mmHg (PO2), -39 mV/decade (PCO2), and 51 mV/pH (pH); low drift; and a functional lifetime of > 2 months. The analytical precision in the physiologically expected range is better than 2 mmHg for the PO2 and PCO2 sensor, and 0.02 pH unit for the pH sensor.

Biosensing Techniques↗
PubMed1992

Polymeric membranes for silicon based (bio)sensors.

During the last decade, chemical and biochemical sensor research has benefited from the availability of new technologies and materials. New embodiments of classical devices have resulted from the use of e.g., solid state technology for the realization of the transducers. In this paper we describe several examples of membrane deposition techniques used in connection with planar, silicon based electrochemical transducers. Casting and electrochemical deposition of glucose oxidase containing membranes are described for the fabrication of glucose enzyme electrodes. Photolithographic patterning of polyacrylamide hydrogel and of siloxane based gas permeable membrane is used for the realization of an amperometric oxygen sensor and an ISFET-based pCO2 device. The last example is that of a free-chlorine sensor for which the photolithographic patterning of the polyHEMA hydrogel layer is described.

Animals↗
PubMed1991

In-vivo behaviour of hypodermically implanted microfabricated glucose sensors.

The in-vivo behaviour of microfabricated GOD (glucose oxidase)/H2O2 glucose sensor implanted subcutaneously in normal anaesthetized rats has been studied. The sensor consists of a planar, three-electrode microcell, an enzyme membrane (glucose oxidase and bovine serum albumin cross-linked with glutaraldehyde) and an outer diffusion limiting polyurethane membrane. The sensor behaviour during hyperglycaemic (13.8 mM and 11.2 mM), euglycaemic (7.8 mM) and hypoglycaemic (3.5 mM) plateau levels was determined. The values of the in-vivo sensitivity (0.64 +/- 0.05 nA/mM) and background current (1.25 +/- 0.4 nA) were determined using a two-point calibration method and then used to calculate apparent subcutaneous glucose concentrations. The results show the presence of a good correlation between all the plasma glucose levels (G) and the apparent subcutaneous tissue concentrations (G'), with G' = 0.997.G - 0.066, r = 0.9782.

Animals↗
PubMed1989

In vivo response of microfabricated glucose sensors to glycemia changes in normal rats.

A planar glucose sensor based on an amperometric detection of H2O2 is presented. The transducer part which is a planar three-electrode cell consisting of two Pt-electrodes and one Ag/AgCl-thin film electrode is realized using microelectronic technology. The overall dimensions are 0.8 mm x 3 mm x 0.38 mm and the working electrode area is 0.1 mm2. GOD is immobilized using glutaraldehyde as a cross-linking agent and bovine serum albumin as a carrier protein. The resulting membrane has a typical thickness of 25 microns. Also, an outer polyurethane membrane is dip-coated all around the tip of the electrode. The influence of pO2 on the sensor response as well as the sensor temperature coefficient, sensitivity and linear range have been investigated. The sensor has been tested in vivo in a subcutaneous tissue of anaesthetised rats. During experiments, blood sampling allows to measure changes in venous plasma glucose using a Beckman analyzer. The sensor response following hyperglycaemic clamps as well as intravenous glucose loads is discussed.

Animals↗