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Experimental Study of Three-dimensional Dynamics of Active Particles

Periodic Reporting for period 1 - ACTIVEMOTION3D (Experimental Study of Three-dimensional Dynamics of Active Particles)

Reporting period: 2017-04-01 to 2019-03-31

The project ACTIVEMOTION3D studies the behaviour of microswimmers in three dimensional (3D) complex environments. Microswimmers are microscopic objects capable of using the energy from their surrounding mediums for directed motion, namely active motion. They provide an ideal system to study far-from- equilibrium physics and have exciting applications in from statistical physics and soft matter to biomedicine and robotics. For example, the active motion of artificial microswimmers can be used for targeted drug-delivery at micro/nanoscale to improve healthcare.

So far, almost all experimental studies of active motion involving either artificial microswimmers or micro-organisms such as bacteria have focused on their behaviour in 2D environments. However, their behaviour is theoretically predicted to be quantitatively different in more realistic 3D environments, which lacks experimental investigation. This is because of the limitations in employed microscopy techniques for 3D imaging in terms of high speed and depth resolution requirements.

This project is aimed at specifically bridging this gap by building a customized light- sheet microscope with fast 3D imaging capabilities to study active motion in 3D complex environments. The experiments to study the behaviour of artificial microswimmers, first in homogeneous environments (water solution) and then in viscoelastic mediums will lead to understanding the under-lying physics behind such systems.
The overall objective of ACTIVEMOTION3D is to utilise the understanding gained from these experiments for wide range of applications from statistical physics and soft matter to targeted drug-delivery in biology and biomedicine.2028
The project ACTIVEMOTION3D is strongly based upon the proposed state-of-the-art light sheet microscope to perform experiments on microswimmers in 3D. The secondment at ICFO-The institute of Photonic Sciences played a crucial role in learning the necessary skills to build the customised light-sheet microscope at the host institute (University of Gothenburg-UGOT). The overall design and imaging parameters of the set-up, such as resolution, speed and magnification were optimised based on the objectives of the project.

Following the successful secondment at ICFO in the beginning of the project, the set-up was successfully implemented at UGOT. The basic light-sheet microscope was functioning by the end of the first year and only the wavefront-coding method remained to be implemented. The wavefront-coding method is crucial to the final aim of the project in terms of imaging speed required to monitor artificial microswimmers in complex environments. The implementation of the wavefront-coding method was specifically challenging and required more time.

The implemented light-sheet microscope was also used for establishing new collaborations, oriented towards interdisciplinary research. One of the most exciting development of modern micro-bio-technology are organoids, where organ specific cells are cultured in 3D cultures, thus representing more physiologically relevant cellular properties compared to conventional 2D cell cultures. These organoids offer several advantages in terms of studying organ specific cells and their response to toxic and non-toxic drugs among many others. However, current methods require physical sectioning of these organoids to study their properties and responses, meaning separating the cells from their physiologically relevant environments. This restricts the scope of such studies because the cells have to be taken out of the organoids for various physiologically relevant studies and several studies can not be conducted on the cells from the same organoids.

The newly established light-sheet microscope was used for proof-of-principle experiments on liver organoids (acquired from collaborators at the university hospital) to demonstrate the advantages of optical sectioning in acquiring live images of biological samples. It was shown that the possibility to eliminate physical sectioning of organoids open up new avenues for more detailed study of cells growing in 3D, such as organ development and disease progression in organoids with infected cells.
The proposed light-sheet microscope of the project ACTIVEMOTION3D has been completed along with the wavefront coding method. The experiments with artificial microswimmers are ongoing currently. Until the end of the project, basic understanding of the behaviour of microswimmers is expected to be gained. These results may have penitential impact on various applications with societal impact, however more extensive experimental tests must be conducted before employing such applications.