PROOF OF CONCEPT OF A NOVEL OPTICAL GLUCOSE ENZYME-BASED MICRO-BIOSENSOR USING SU-8

A novel one-step microfabrication process of SU-8 films for the development of inexpensive light-weight and small size optical glucose micro-biosensors is proposed. Experimental work was carried out in order to investigate whether SU-8 photoresists, which are polymers widely used in MEMS applications, can be utilised as immobilisation matrices for the simultaneous encapsulation of glucose oxidase and an oxygen-sensitive fluorescent indicator. The immobilisation of the enzyme, the encapsulation of the indicator and the patterning of the custom-made SU-8 take place simultaneously, thus simplifying the microfabrication process.

Simulteanous enzyme immobilisation and micro-nanofabrication process for low-cost biosensor applications

Nico de Rooij, Sotiria Psoma, Peter Van der Wal

Biosensors which are based on BioMEMS combine developments in micro-nanotechnology and biological recognition elements, in order to enable the measurement of low level analyte concentrations with portable detection-systems. A major challenge of such small biochips is the accuracy of the sensing process. The main aim of the present research project was the investigation and development of novel low cost matrices based on custom-made SU-8 polymer for simultaneous microfabrication and immobilisation of enzymes in order to form the basis for the development of novel low-cost micro-nano-biosensors. The negative photoresist SU-8 was utilised because of its attractive characterestics such as stability under environmental conditions, biocompatibility and low cost. The entrapment of biological molecules into the SU-8 structures was experimentally assessed using the enzyme glucose oxidase; and, electrochemical and optical sensing techniques were employed. The major emphasis of the experimental studies was on selectivity, sensitivity and stability improvements as well as on the optimum design, and microfabrication process. A detailed investigation of the optimum microfabrication process and composition of biocompatible SU-8 matrices with encapsulated enzyme such as glucose oxidase was carried out. The conditions of the various steps of the SU-8 processing are hostile to the enzymes’ survival. Improving the process conditions and encapsulation matrices were primordial for the success of this work. This study implied variation in enzyme concentration matrices in order to improve the activity of the encapsulated enzyme inside the matrix. Different sacrificial materials for SU-8 and their influence on the used enzyme and on the products of enzymatic reactions were investigated.

2013

Microfabrication d'objets composites fonctionnels en 3D et à haut facteur de forme, par procédés UV-LIGA et microstéréolithographie

Sébastien Jiguet

The present thesis deals with new composite photoresists for the UV-LIGA and microstereolithography microfabrication processes. The aim is to build functional 3D objects, with high aspect ratio. Two projects have been investigated in parallel for each microfabrication process. Their similitude is the use of dry or colloidal particles to prepare photosensitive formulations. The first project is focused on the well-known negative tone photoresist SU-8. This epoxy resin is used for the UV-LIGA processes, because of its high aspect ratio. As a thick photoresist, the main applications of the SU-8 are for moulding or for making inert structures (supports). However, the SU-8 structures show some cracks and unstickings of the substrate, due to the internal stress of the epoxy resin, which is the main disadvantage of the SU-8 photoresist. In order to avoid or to decrease the cracks, silica particles have been dispersed into the photosensitive matrice. The new composite photoresist is photosensitive to UV irradiations, and allows the fabrication of composite structures, which show a better adhesion on quartz, and silicon substrates, and a better sonication resistance. The SU-8 photoresist is also used for packaging applications as a non functional material, because of its electrical isolation properties. The idea to enhance its electrical conductivity comes from its high aspect ratio and the aim to microfabricate, directly, electrical structures without a moulding step. Silver particles have been used to make a photosensitive composite material, which can be applied to the UV-LIGA process. The obtained structures are electrically conductive, even at a low percolation threshold (6%vol.), and their thicknesses range up to 20 µm. It has been shown that electrodes and screens for absorbing electromagnetic waves are possible. The second project is focused on the microfabrication of 3D complex objects by microstereolithography. These objects are usually in polymer and to widen their applications to the biomedical world, alumina particles have been added to the photoresist, a photosensitive acrylate resin. Ceramic composite objects with complex form have been built by the integral microstereolithography, and their resolution is similar to the one of polymer objects. In order to obtain ceramic objects, photosensitive composite formulations need to be highly loaded in alumina powder. That induces rheological problems, such a higher viscosity, which have been overcome by modyfying the microstereolithography process. After a thermal treatment, the ceramic composite objects, highly loaded are transformed into ceramic objects without any deformations, and cracks.

EPFL2004

A novel enzyme entrapment in SU-8 microfabricated films for glucose micro-biosensors

Olivier Frey, Sotiria Psoma

The present work investigates the utilisation of the widely used SU-8 photoresist as an immobilisation matrix for glucose oxidase (GOx) for the development of glucose micro-biosensors. The strong advantage of the proposed approach is the simultaneous enzyme entrapment during the microfabrication process within a single step, which is of high importance for the simplification of the BioMEMS procedures. Successful encapsulation of the enzyme GOx in "customised" SU-8 microfabricated structures was achieved through optimisation of the one-step microfabrication process. Although the process involved contact with organic solvents, UV-light exposure, heating for pre- and post-bake and enzyme entrapment in a hard and rigid epoxy resin matrix, the enzyme retained its activity after encapsulation in SU-8. Measurements of the immobilised enzyme's activity inside the SU-8 matrix were carried out using amperometric detection of hydrogen peroxide in a 3-electrode setup. Films without enzyme showed negligible variation in current upon the addition of glucose, as opposed to films with encapsulated enzyme which showed a very clear increase in current. Experiments using films of increased thickness or enzyme concentration, showed a higher response, thus proving that the enzyme remained active not only on the film's surface, but also inside the matrix as well. The proposed enzyme immobilisation in SU-8 films opens up new possibilities for combining BioMEMS with biosensors and organic electronics. (C) 2010 Elsevier B.V. All rights reserved.

Elsevier2010

Microfabrication d'objets composites fonctionnels en 3D et à haut facteur de forme, par procédés UV-LIGA et microstéréolithographie

Sébastien Jiguet

EPFL2004