Wim Laureyn

Nanoscaled interdigitated electrode arrays for biochemical sensors

Abstract Nanoscaled interdigitated electrode arrays were made with deep UV lithography. Electrode widths and spacings from 500 down to 250 nm were achieved on large active areas (0.5×1 mm). These electrodes allow for the detection of affinity binding of biomolecular structures (e.g. antigens, DNA) by impedimetric measurements. Such a sensor with Pd electrodes on SiO 2 is developed and theoretically analysed. It was experimentally characterised in KCl solutions demonstrating its bulk-insensitive behaviour and the immobilisation of glucose oxidase (GOD) could be monitored by measuring the double layer impedance.

Impact of spacers on the hybridization efficiency of mixed self-assembled DNA/alkanethiol films

The immobilization of DNA strands is an essential step in the development of any DNA biosensor. Self-assembled mixed DNA/alkanethiol films are often used for coupling DNA probes covalently to the sensor surface. Although this strategy is well accepted, the effect of introducing a spacer molecule to increase the distance between the specific DNA sequence and the surface has rarely been assessed. The major goal of this work was to evaluate a number of such spacers and to assess their impact on for example the sensitivity and the reproducibility. Besides the commonly used mercaptohexyl (C(6)) spacer, a longer mercapto-undecyl (C(11)) spacer was selected. The combination of both spacers with tri(ethylene)glycol (TEG) and hexa(ethylene)glycol (HEG) was studied as well. The effect of the different spacers on the immobilization degree as well as on the consecutive hybridization was studied using surface plasmon resonance (SPR). When using the longer C(11) spacer the mixed DNA/alkanethiol films were found to be more densely packed. Further hybridization studies have indicated that C(11) modified probes improve the sensitivity, the corresponding detection limit as well as the reproducibility. In addition two different immobilization pathways, i.e. flow vs. diffusion controlled, were compared with respect to the hybridization efficiency. These data suggest that a flow-assisted approach is beneficial for DNA immobilization and hybridization events. In conclusion, this work demonstrates the considerable impact of spacers on the biosensor performance but also shows the importance of a flow-assisted immobilization approach.

Discrimination of specific and non-specific bindings by dielectrophoretic repulsion in on-chip magnetic bio-assays.

Affinity binding is the principle used in a large number of bio-assays. Aside from specific bindings, non-specific bindings usually deteriorate assays by giving false positive signals and restrict the detection limit. Currently, the assay specificity is mainly dependent on the effectiveness of a suitable surface chemistry. We report an approach to discriminate specific and non-specific bindings with dielectrophoretic (DEP) forces for on-chip magnetic bio-assays. Conjugated to the analytes, magnetic particles were used as the agents for DEP force generation. Due to a weaker binding strength, the non-specifically bound particles were removed while specific bindings remained intact. Analytical and finite element calculations were also performed to study all relevant forces. Furthermore, the removal of magnetic particles was also assessed by measuring the magnetic signal using magnetoresistive sensors. This technique can not only be used to improve the specificity of the on-chip bio-assays but also be developed as a tool of force spectroscopy for the study of bio-molecular binding physics.

Characterization of Nanoscaled Interdigitated Palladium Electrodes of Various Dimensions in KCl Solutions

Nanoscaled interdigitated electrodes (IDEs) were developed for the purpose of being used as miniature and sensitive affinity biosensors. IDEs with palladium as the electrode material on a SiO2 substrate were made with electrode widths and spacings ranging from 550u2005nm down to 250u2005nm. These sensors were theoretically modeled, enabling the prediction of their impedimetric response in KCl solutions. The strength of the theoretical model was proven by a characterization of IDEs of various dimensions in KCl solutions of different concentrations. The results demonstrate a quite reproducible behavior and a correlation between the impedimetric response in KCl solutions and the electrode dimensions.

Investigation of protein adsorption with simultaneous measurements of atomic force microscope and quartz crystal microbalance

We have combined the tapping-mode atomic force microscope (AFM) and quartz crystal microbalance (QCM) for simultaneous investigation and characterization of protein adsorption on various metallic surfaces using these two instruments. The adsorption of proteins such as human plasma fibrinogen and anti-human immunoglobulin onto the metal or oxide/QCM surface were monitored using both methods at the same time when varying the concentration of proteins. The combination of AFM with QCM allowing the simultaneous measurements with two techniques working at very different scales and probing different properties of the adsorbed layer provides quantitative and qualitative information that can distinguish different protein adsorption behavior.

A wet release process for fabricating slender and compliant suspended micro-mechanical structures☆

This paper reports on the development of a generic wet release process for the fabrication of suspended slender and compliant micromechanical structures of poly-SiGe, poly-Si and aluminium with thickness values in the range 0.5–2 mm and gap spacing from 0.5 to 2 mm, respectively. A self-assembled monolayer (SAM) of n-decyltrichlorosilane (DTS) is used as an anti-stiction material. Process characterisation studies include DTS SAM characterisation, release of polycrystalline silicon germanium test structures, polycrystalline silicon device structures on silicon substrate and Aluminium test structures on AF45 glass substrate. We have obtained work of adhesion values of 0.06, 11, and 1 mJ/m 2 , slenderness ratio (SR) values of 3464, 752.2, and 2061, compliance (C) of 2100, 12, and 120 m/N, and contact angle of 1298 ,1 268, and 110.38, for poly-SiGe, poly-Si and aluminium cantilevers respectively. Our results compare favourably well with results from the literature. # 2003 Elsevier Science B.V. All rights reserved.

Cost effective realization of nanoscaled interdigitated electrodes

Nanoscaled interdigitated electrodes (IDEs) are being developed for the realization of miniaturized and highly-sensitive affinity biosensors. Until now, nanoscaled IDEs have been realized on silicon wafers using deep UV lithography or e-beam patterning. However, for many applications in the biochemical field there is a strong need for cheap and/or disposable sensor devices. Therefore, a new, cost effective fabrication method for nanoscaled IDEs, which can also be applied on cheap, micro-moulded plastic substrates, has been developed. The method is based on the directionality of a vacuum evaporation process and omits expensive lithography steps completely. The feasibility of this electrode deposition technique has been proven by realizing IDEs on silicon substrates. Future work is focused on the realization of IDEs on injection moulded plastic substrates.

Development of microelectronic based biosensors

Biosensors offer the opportunity to sense the biological world providing valuable information for medical diagnostics, analytical chemistry, environmental monitoring and fundamental research. Convergence of engineered (bio)chemical surfaces with micro- and nano- systems promises tremendous advances and potential cost reductions in biotechnology. This paper introduces some key challenges facing biosensor development, focussing on opportunities that arise from microsystem platforms utilising novel materials and processes. Examples from our work are presented illustrating the implementation of acoustic wave sensors and novel FET-type sensors.