SMD

Single or few molecules detection by combined enhanced spectroscopies

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 Obiettivo del progetto (Objective)

'Future breakthroughs in the understanding of fundamental biological processes causing major diseases are expected from the development of miniaturized probes or microscopes able to detect and identify a single or a small number of molecules. The SingleMoleculeDetection (SMD) proposal will develop a unique device able to perform simultaneously and in a dynamic way force and spectroscopic measurements. We will design and fabricate novel devices for the generation of plasmon polaritons as well as combine photonic crystals and plasmonic nanolenses. These new devices will be able to detect few/single molecules through Raman, InfraRed and Terahertz (THz) signals and in combination with Atomic Force Microscopy and Optical Tweezer force spectroscopy with a spatial resolution in the sub-10 nm for Raman and IR and sub-100 nm for the THz region. The complete characterization of single unknown molecule will be demonstrated through: i- investigations on the chemical and physical properties of membrane receptors, such as rhodopsin, odorant receptors and ionic channels; ii- identification of new molecules involved in cancer development and metastasis. The new devices will allow the acquisition of THz images and we will explore the possibilities of this new spectral region for biomedical scanning. The SMD proposal is based on an original idea of the coordinator, prof. E. di Fabrizio and will be exploited thanks to the complementary expertise present in the different sites and to a tight coordination between the various groups. The design, fabrication and testing will be performed at UMG, TASC and CBM Integration in a single instrument will be carried out at TASC, CBM, IIT Nanotec, RUB. Validation activities will be performed by all the partners taking advantage of the world leading expertise of the TUDO and the STRATH- AC in spectroscopy of natural and artificial biological systems. The SME NANOTEC and CBM will provide the commercial exploitation of the obtained results.'

Introduzione (Teaser)

A greater understanding of how individual molecules behave in biological systems will have significant implications for health care by opening up new avenues for intervention. A European consortium is contributing to this by developing new high-resolution devices that facilitate the detection of single molecules.

Descrizione progetto (Article)

The detection and characterisation of single molecules would facilitate research of fundamental biological processes and enable the recovery of structural information of membrane proteins. Moreover, diagnosis of many diseases including cancer could be improved.

To achieve this, scientists of the EU-funded 'Single or few molecules detection by combined enhanced spectroscopies' (SMD) project proposed to confine a high electromagnetic field in an extremely small portion of space to provide sensitive chemical mapping at the nano-scale level. To this end, they explored the properties of surface plasmon polaritons (SPPs), which are in essence electromagnetic waves created when light particles, also known as photons, impinge on metal plasmons under appropriate conditions.

The idea was to combine different experimental spectroscopy techniques in a single device so as to achieve label-free chemical characterisation at the single-molecule level. This system combines the technology of an atomic force microscope or an optical tweezer with optical spectroscopy, and allowed simultaneous dynamic way force and Raman, SERS, infrared or terahertz measurements. The spatial resolution achieved reached an unprecedented low level in the range of 10 nanometres or smaller.

Alongside the optimisation of the components, scientists synthesised an array of nanoprobes based on protein or DNA conjugates with metal ions. These were tested to obtain structural information and to characterise the conformational changes of the photoreceptor transmembrane protein in the cyclic nucleotide-gated ion channel. Additionally, by exploiting the BRCT domain proteins as probing molecules, researchers were able to distinguish the wild type from mutated peptides.

By successfully combining optical and mechanical (spectroscopic) characterisation methodologies in a single device, the SMD initiative addressed a significant technological challenge. Single-molecule spectroscopy has the potential to enhance diagnosis sensitivity and open up new avenues for pharmaceutical companies and industries interested in health care.