In this line of research, after five years of intensive work, the first nanomechanical spectrometer has been developed.

ESI ionisation is used to generate charged species mainly desolvated at ambient pressure, and the charged species were then guided to a tiny nanomechanical detector. The spectrometer is based on the identification of intact biological entities by a dual signature: mass and rigidity (instead of the mass-to-charge ratio used by conventional mass spectrometers in biology). It overcomes the fundamental limitations of conventional mass spectrometry: it does not require sample fragmentation and is insensitive to loading. Proof of concept was demonstrated with gold nanoparticles and E. coli bacteria (Nature Comm. 7, 13452, (2016)). Next steps are the discovery of protein cancer biomarkers in plasma and the unbiased detection of emerging pathogenic viruses such as HIV, Zika or Ebola in clinical samples. This activity is currently funded by European projects (ERC-Co-2016-LIQUIDMASS-681275 and FETPROACT-2016-VIRUSCAN-731868).

In this line, cavity optics, plasmonic effects and nanomechanics are combined on the surface of tailor-made silicon microcantilevers to develop an ultra-sensitive sandwich immunoassay labelled with gold nanoparticles. The presence of the biological analyte in the sample is revealed by i) a dramatic increase of the sensor’s brightness in the darkfield microscope in a particular colour and ii) a shift of its natural mechanical frequency due to the «weight» of the nanoparticles. The immunoassay achieves a detection limit of 10-7 ng/ml in serum with cancer biomarkers such as PSA and CEA, which is at least five orders of magnitude lower than that achieved in routine clinical practice. False positives and negatives are less than 0.1%. This milestone has been published in Nature Nanotechnology (vol. 9, p1047 (2014)) and has been featured by the journal as News & Views. Immunoassays have also been applied to early detection of HIV just one week after infection (PLOS One 12, e0171899 (2017)), proving the sensors’ figures of merit for clinical research. Clinical trials have been initiated for early detection of lung and breast cancer. Research has been funded by national projects and associations (AECC, Asoc. Helena Torres).

Research into the mechanobiology of cancer is providing increasing evidence of how the mechanical properties of cells and the interaction forces between cells and the microenvironment play an essential role in cancer. We develop new technologies based on optomechanical systems, force microscopy and digital holography microscopy to fingerprint cancer cells through universal mechanical properties and to find the mechanical interactions that aid tumour progression. We have recently described the intimate link between cell mechanics and malignancy in breast epithelial cell lines (ACS Nano 10, 3365 (2016)). From this line of research, we hope to develop innovative tools for cancer diagnosis and treatment. This research line has been funded by the ERC programme (NANOFORCELLS- ERC-StG-2011-278860 and LIQUIDMASS-ERC-CoG- 681275).

Knowledge transfer: To ensure the exploitation of the results, the most relevant analytical tools developed by the group are patented and licensed to spin-off companies founded by members of the group, such as MecWins S.A (www.mecwins.com) part of the Grifols group and with a stable collaboration with Quidel (USA) which develops instrumentation for clinical diagnosis.