Résumé des résultats (Abstract)
(Anglais)
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This project intends to take advantage of the mechanical properties of micro- and nano-mechanical structures (cantilevers) to measure molecular (ligand-receptor) interactions. Such measurements would have applications in fields such as health and clinical diagnosis, environmental monitoring, detection of illicit materials and food safety. Within those application areas, the project will concentrate on the clinical diagnosis field, with two specific applications: the detection of tumour-associated protein and the detection of viruses. These applications have been selected because the partners already have specific know-how in those areas.
Objectives:
The main objectives of the project are:
i) to develop versatile, inexpensive, and easy-to-use diagnostic tools for health, environmental and other applications based on the measurement of molecular interactions (ligand-receptor itneractions) by integrated micro and nano-cantilever sensors and;
ii) to test the developed diagnostic tools in two specific health care applications, namely:
1) the detection of tumour markers in clinical diagnosis and;
2) the detection of viruses in pre-clinical diagnosis, providing a verification of the project´s achievements and initiating a generation of innovative products with significant market potential.
The proposed project capitalizes on the mechanical properties of micro- and nano-mechanical structures (cantilevers) to measure molecular (ligand-receptor) interactions.
Work description:
1. Development of a microsensor system based on microcantilevers and surface stress detection, for a general purpose instrument. The microcantilevers will be fabricated using CMOS technology plus post-processing. Signal-processing electronics will be integrated on-chip. The CMOS processing will be subcontracted to a commercial foundry. This approach has the advantage of a straight forward route to commercial fabrication of the devices, and of a common design environment for the sensing devices and the electronic circuits;
2. Development of a microsensor system based on nanocantilevers and force detection, for a high-sensitivity instrument. A technology for the fabrication of sub-micron cantilevers (nanocantilevers) will be developed. Integrated nanocantilevers with signal-processign circuitry will be fabricated. Nanocantilevers will have a much higher force sensitivity that microcantilevers. They will be used in a new approach, in which the binding forces between the functionalized cantilever tip and a substrate-immobilized molecule are directly measured;
3. Development of a diagnosis instrument with the following key features: Usable in-field, hand-held, affordable (disposable bio-specific chip), easily usable, multi-analyte capability.
Two versions will be developed:
A) General purpose instrument for clinical diagnosis, based on the microcantilever sensors;
B) High-sensitivity instrument for pre-clinical diagnosis, based on the nanocantilever sensors;
4.Tests in specific applications.
The sensors and instruments developed using micro- and nano- cantilevers will be tested in two specific clinical diagnosis problems:
i) Detection of a tumour-associated protein, the prostate-specific antigen (PSA). It will be used the instrument approach A, based on microcantilevers;
ii) Detection of a virus, the equine herpes virus. It will be used the instrument approach B, based on nanocantilevers.
Milestones:
Development of the technology to fabricate miniaturized sensors based on micro- and nano- cantilvers for clinical and pre clinical assays.
Development of a portable, easy-of-use instrument for performing clinical diagnoses based on the above sensor.
Test of the instrument in two already defined applications: the detection of tumour marker in clinical diagnosis and the detection of viruses in pre-clinical diagnosis.
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