PIRO · Phototransient InfraRed Holography (PIRO)

Molecules are the fundamental building blocks of life: disease is intrinsically linked to molecular malfunction and, sometimes, a tiny molecular error in a single cell can kill an organism. Drugs, such as antibiotics, are designed to protect us: they rid us of pathogens by disrupting their molecular machinery. If unsuccessful, surviving bacteria might adapt to evade future attacks and a few resistant bacteria can cause great damage. Everything mentioned above relies on specific molecular changes. A technique that could rapidly visualise them holds great promise: it would allow us to specifically target this one deadly cancer cell or adopt antibiotics treatment before resistance emerges. Vibrational imaging, which combines spatial cues with molecular resolution, is the prime-candidate for revealing this molecular stand-off: Spontaneous Raman readily acquires broadband spectra but is too slow to interrogate large samples. Coherent Raman can measure them but lacks spectral resolution. Finally, Fourier transform infrared microscopy combines spectral resolution and speed but its spatial resolution is insufficient.PIRO promises to deliver the necessary tool for the job by combining concepts from nonlinear ultrafast spectroscopy and digital holography. PIRO implements a novel vibrational imaging platform: a phototransient infrared holographic microscope (PIROscope). The PIROscope, inspired by our recently introduced ultrafast holographic microscope, combines femtosecond IR-excitation with visible readout to, ultimately, retrieve spectrally resolved quantitative images with an unprecedented combination of imaging speed, spectral observation window and spatial-resolution. During PIRO we will implement the PIROscope and validate it for biomedical imaging. We will then use our edge over the state-of-the-art to take first steps towards PIRO-based diagnostics by high-resolution visualising breast cancer tissue and the metabolic activity of antibiotics-treated bacteria.