Up-conversion ferroelectric nanocrystals for optical sensing of electric potential in biological systems – UFO

Most living cells exhibit a difference in electrical potential across their plasma membrane resulting from differences in ion concentration maintained by ion channels and pumps. The membrane of a neuron can be suddenly (˜1 ms) depolarised (its intracellular potential rising from -70 mV to +30 mV) by the synchronised opening of these channels, stimulated by other neurons, thus generating an 'action potential' that spreads to other cells to which that neuron is connected by synapses. Monitoring this depolarisation thus provides information on synaptic transmission, which is essential for cognitive and neuromotor processes. The classical approach consists of measuring electrophysiological activity using micropipettes on a few cells at a time ("patch-clamp"), or with a microelectrode array able to record the extracellular potentials of a group of neurons.
In recent decades, optical measurement methods have been introduced to obtain the electrical activity of a large number of cells simultaneously with high resolution. Apart from a few works exploiting the modulation of electroplasmonic effects of gold nanoparticles or semiconductor nanocrystal charges, these methods present a certain number of drawbacks (photobleaching, toxicity...) or limitations regarding the measurement of an extracellular electrophysiological signal.

The objective of our project is to develop and biologically validate a new photoluminescent probe of the extracellular potential based on a transduction mechanism never explored for this application and which should lead to a very high spatiotemporal resolution. These probes are ferroelectric nanocrystals (FENC) doped with rare-earth ions (RE3+) whose spectral modulation of photon up-conversion (UC) will be detected as a function of the surrounding electrical potential. The variations of this potential, under the effect of the opening of the ion channels, modify the surface density of the polarization charges P of the FENC, making P vary which in turn leads to a deformation of the FENC by inverse piezoelectric effect, inducing finally a change of intensity of certain emission lines of UC. This process is supported by our recent observation of such a UC modulation in an FNCE exposed to an electric field.

First, we will synthesize BaTiO3 NCFEs of size˜200 nm doped with Er3+ and Yb3+ ions and also test other matrices with stronger piezoelectric response, and other dopants. Ab initio calculations will help us determine the most favourable crystallographic sites for ion incorporation. We will characterise the intensity of the CU and its lifetime. Next, we will image the ferro/piezoelectric domains of individual NCFEs by piezoelectric force microscopy (PFM) where an oscillating potential is applied to the tip. We will aim to produce bright single-domain FENCs. We will quantify the variation of the UC spectrum during PFM measurements, as well as under ion flux from a discharge tip. Finally, we will test the ability of FENCs to detect changes in charge density in solution, before using them, after biofunctionalization, as optical sensors of near-membrane potential changes during electroporation, and then to monitor nerve regeneration.

This highly interdisciplinary project requires the complementary skills of five teams, in the synthesis and characterisation of FENCs, optical spectroscopy and near-field probe microscopy, bio-conjugation of nanoparticles and bioelectrochemistry. This project exploiting the polarisation charges of ferroelectric nanosystems will open up a new field of applications beyond the biomedical one.