Periodic Reporting for period 1 - FLAMMES (On-chip metasurface-based neuroimaging platform toward high-throughput drug screening in freely behaving animal)
Reporting period: 2021-04-01 to 2023-03-31
Neurological and psychiatric disorders are clinical areas where the probability of novel drugs discovery, and indeed effectiveness, is among the lowest in the field of pharmacological development over last decades. A strategy for monitoring both the whole-brain dynamics and the behavior of zebrafish larvae can help to map both the actual interaction mechanisms between the neuronal activities and the behavior, as well as the impact of different neuro-specific drug on their behaviors.
Goal of this project is to develop a “miniaturized microscope” (FLAMMES) capable of producing whole-brain imaging of zebrafish larvae and compatible with behavioral studies, such to open to the possibility of automatically processing and evaluating, at the same time, the effects of many compounds on their biological activities in a large number of organisms. The key enabling technology of this platform is the integration of state-of the-art CMOS imaging sensors with metasurfaces, flat optical components with multiplexing and tunable properties.
Goal of this project is to develop a “miniaturized microscope” (FLAMMES) capable of producing whole-brain imaging of zebrafish larvae and compatible with behavioral studies, such to open to the possibility of automatically processing and evaluating, at the same time, the effects of many compounds on their biological activities in a large number of organisms. The key enabling technology of this platform is the integration of state-of the-art CMOS imaging sensors with metasurfaces, flat optical components with multiplexing and tunable properties.
During the first part of the project, in collaboration with the HI and the Secondment lab, I designed, fabricated and characterized a novel metasurface-based illumination module. Specifically, I first developed a novel method to generate structured light distributions known as Bessel beam lattices by modulating the light wavefront phase on a single optical plane. This represented the building pillar opening the possibility to integrate the currently bulky optical layouts in small footprint configurations. Afterward, I focused on the development of a computational pipeline for translating the phase correction in a layout compatible with the metasurface technology. At the end of the first part of the project I focused on the development of a novel nanofabrication process flow to fabricate the designed optical element on dielectric metasurfaces with silicon nitride on silicon dioxide substrates. We realized that the developed approach along with the specific aims of the project, was also of interest for other fields outside the neurobiology field such as light-based material processing and optical microscopy in general.
With the prototypes designed and developed in the first part of the project, during the second part of the project at the HI, I worked on the integration of the metasurface-based optical element into a custom made up-right microscope to enable lattice light microscopy of the zebrafish brain. I challenged myself using the developed element for optical recordings of neuronal activity from a living organism. For this I learned the optical techniques and sample handling for working with calcium-based fluorescent reporters of neuronal activity. Then, I developed an experimental protocol to optimize the zebrafish larvae imaging conditions, a software framework for the acquisition and the analysis of the acquired dataset. I obtained with the developed optical element recordings of the neuronal activity with cellular resolution.
I disseminated the project results presenting my work at two international conferences with two oral presentations. Moreover, I launched and leaded a multidisciplinary program (FNIP program, https://fnip.biomed.unipd.it/) to favor a scientific exchange and networking opportunities for future collaborations.
With the prototypes designed and developed in the first part of the project, during the second part of the project at the HI, I worked on the integration of the metasurface-based optical element into a custom made up-right microscope to enable lattice light microscopy of the zebrafish brain. I challenged myself using the developed element for optical recordings of neuronal activity from a living organism. For this I learned the optical techniques and sample handling for working with calcium-based fluorescent reporters of neuronal activity. Then, I developed an experimental protocol to optimize the zebrafish larvae imaging conditions, a software framework for the acquisition and the analysis of the acquired dataset. I obtained with the developed optical element recordings of the neuronal activity with cellular resolution.
I disseminated the project results presenting my work at two international conferences with two oral presentations. Moreover, I launched and leaded a multidisciplinary program (FNIP program, https://fnip.biomed.unipd.it/) to favor a scientific exchange and networking opportunities for future collaborations.
Along with the research and dissemination activities, during the project, I worked on one patent application and two publications.
A patent request has been submitted with the title “Metodo per la generazione di un reticolo di fasci Bessel” (ref. num. BI5740R). The invention relates to a method for rendering 1D/2D/3D lattices of quasi-Bessel beams by means of one single, flat (sub-millimetric scale), and lightweight (gram scale) optical element. More specifically, the present optical system uses a special design of the phase spatial distribution to generate a series of non-diffractive beams in its far field. Each beam of the lattice produced with this method can be engineered with independent optical properties and positions.
This invention opens new application scenario (e.g. material processing, telecommunication, and microscopy) requiring structured illumination with multiple beams with higher depth of focus and lower lateral size width respect to solution based on conventional bulky lenses.
An article with the title “Generation of Bessel beam lattices by a single metasurface for neuronal activity recording in zebrafish larva” has been submitted to a peer-reviewed journal and one other article has been published ("Thermally reconfigurable metalens").
A patent request has been submitted with the title “Metodo per la generazione di un reticolo di fasci Bessel” (ref. num. BI5740R). The invention relates to a method for rendering 1D/2D/3D lattices of quasi-Bessel beams by means of one single, flat (sub-millimetric scale), and lightweight (gram scale) optical element. More specifically, the present optical system uses a special design of the phase spatial distribution to generate a series of non-diffractive beams in its far field. Each beam of the lattice produced with this method can be engineered with independent optical properties and positions.
This invention opens new application scenario (e.g. material processing, telecommunication, and microscopy) requiring structured illumination with multiple beams with higher depth of focus and lower lateral size width respect to solution based on conventional bulky lenses.
An article with the title “Generation of Bessel beam lattices by a single metasurface for neuronal activity recording in zebrafish larva” has been submitted to a peer-reviewed journal and one other article has been published ("Thermally reconfigurable metalens").