NMP4-CT-2005-017114

RECEPTRONICS, is a project financed by the VIth European Research WorkProgram involving 9 partners from European Institutions, namely: ARCES University of Bologna (Coordinator), Centre National de la Recherche Scientifique - CNRS Grenoble (FR), DSV and LETI laboratories at Commissariat à l’Energie Atomique - CEA Grenoble (FR), National and Kapodistrian University of Athens - NKUA (GR), EE and Chemistry Departments of University of Southampton (UK), Silicon Biosystems, S.p.A. (IT), and SPI-BIO (FR).

The total cost of the RECEPTRONICS project is 3.5M€ with a grant of 2M€ from EC. The goal is to develop low-cost, label-free biomolecular sensors by integrating concepts and methods from bio-nanotechnology and microelectronics. The RECEPTRONICS project is based on a strong multi-disciplinary platform where integration of knowledge from Biology, Physics, and Information Technologies is required.

The project is aimed to achieve the goal of molecular recognition at very low levels of concentration. In this specific task, state-of-the-art artificial systems cannot compete with living organisms. As an example, the sensitivity of chemical senses in insects is 100 billions greater than state-of-the-art electronic noses. Even if not to this extent, the project proposes to reduce the huge gap between Nature and Technology.

State-of-the-art nose technology is currently based on electrical conducting polymers - materials which are similar to plastics but can conduct electricity. These materials can be primed to absorb and respond to different odour molecules, and a typical artificial nose will feature an array of polymer sensors, each of which is responsive to a particular substance. However, odours affect many of the sensors in different ways, and the resulting pattern of responses needs to be analysed. Furthermore, their sensitivity is still relatively low.

The RECEPTRONICS project has picked up the problem from a different angle. The project plan to replicate what goes on in biology. In the nose are cells with molecules embedded in the cell membrane. When these bind with an odour molecule, a hole opens in the molecule and an electrical current flows, creating a stimulus, which is transmitted to the brain.

The researchers will use molecular engineering techniques to create receptors which are sensitive to different substances, based on designs found in animal noses. These receptors will be embedded in membranes in an array, with each receptor linked to an electronic interface which can detect electronic signals transmitted when the receptor binds with its target molecule. The system will be mounted on a credit-card sized chip.

The new nose will have a sensitivity 100 to 1000 times greater than today's electronic noses. The three-year project will focus on designing a system which could be used in medicine to detect hormones, and so help doctors to diagnose a range of diseases. This could be done since molecular recognition is one of the most important steps required for a deep understanding of mechanisms in living beings. Every active cell interacts each other and with the environment by means of a complex network of molecular messangers at very low concentration. There are perhaps thousands or millions of regulatory substances in the human body and any imbalance between them may have dramatic consequences for well-being and health.

The only way to boost the sensitivity for molecular recognition is using affinity binding paradigm employed by receptors. Receptors are proteins that are usually sitting on the cell membrane that are employing an extremely efficient molecular machinery for detecting specific molecules. The goal of the project is to combine efficiency of this bio-molecule with powerful flexibility of integrated electronics in a unique device called Receptron. The Project proponents are strongly convinced that the goal of molecular recognition could only be achieved using several strategies belonging to both Nanotechnology and Information Technology. This is the reason why RECEPTRONICS is organized in a stack of technology objective layers (see figure) where each task is integrated and developed in a strong synergy with others.

Being able to detect specific biological molecules at very low concentrations is a new promising area of Medicine that aims to identify the onset or prediction of disease before the patient shows any symptoms. If the technology can be made cheap and simple enough for widespread use, it will enable the rapid identification and monitoring of proteins and pathogens. As a result, it will be possible not only to give appropriate treatment much more quickly but also to make treatment patient specific, leading to fewer side-effects and faster patient recovery. RECEPTRONICS could provide a breakthrough technology for sophisticated diagnostic tools in the field of early cancer diagnosis and hormone balance monitoring. Furthermore, the same technology could be employed for detecting contaminants at very low concentration for environmental safety in Agriculture and industrial processes.

Results of the first year of the project

The main achievements of the first period have been:

• Validation of synthetic fusion protein design principle. Natural ion channels are artificially coupled with specific receptors. The resulting protein is not existing in living beings, but it can be used to naturally detect target substances at molecular level;

• Design and test of several approaches to electrically address arrays of artificial lipid bilayers and methods for delivering fusion proteins into them. The design has been driven by the requirements to achieve high reliability and reproducibility for industrial applications; Structures with an yield of about 90% have been preliminary demonstrated in the Project.

• Design and test of an extremely compact electronic system for single molecule event detection. The system, as large as a credit card, is the first step for designing efficient and integrated electronics for interfacing bionanosystems;

• Advances for data acquisition and statistical elaboration of molecular signals. This is needed since molecular signalling is intrinsically stochastic and it should be treated with proper tools. Precision below 1% of accuracy for ion channel open probability could be achieved with developed algorithms.

Contacts and information

Project Coordinator:

Prof Marco Tartagni

c/o ARCES University of Bologna, Campus of Cesena

Via Venezia 52, I-47023 Cesena , ITALY

Ongoing status of the project can be found in the website: www.receptronics.org.

Executive Summary 01 2007