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.