Lightsheet Brillouin Nanoscopy: mechano-sensitive superresolution imaging for regenerative medicine

Introduction

Better microscopes have always triggered scientific discovery. Lightsheet microscopy and nanoscopy are no exception and have initiated knowledge jumps in structural and dynamical imaging. However, they do not inform us on mechanical properties.

Current State of Mechano-sensitive Microscopy

The domain of mechano-sensitive microscopy is still in its infancy yet has already unveiled a stark dependence of cellular development on local stiffness and viscoelasticity. For instance, coordinated strain on the sub-millimetre scale is a key ingredient to grow induced pluripotent stem cells into a beating adult cardiac muscle; without such an environment, a twitching heap of cardiomyocytes develops instead.

Research Questions

What are the processes within cells that cause this forked differentiation? How can we optimise the growth of artificial tissue in regenerative medicine? Given the dynamics and 3D nature of the problem, paired with the requirement of sub-cellular resolution, one must conclude that our current instrumentation is not up to the task.

Project Aim

Thus, this project aims to develop a label-free microscopy technique that can image viscoelasticity at unprecedented sub-diffraction resolution inside living, differentiating cardiac tissues at order-of-magnitude faster acquisition speeds than previously possible.

Innovative Approach

This will be made possible by a completely new type of optical element that allows snap-shot hyperspectral imaging at unparalleled speed and sensitivity. Transforming the latest innovations within nanoscopy and lightsheet imaging and using Brillouin scattering as a proxy for viscoelastic tissue properties on the microscale, Lightsheet Brillouin Nanoscopy (LiBriNa) will be the fastest, most gentle, and highest resolution mechanosensitive microscope ever built.

Broader Impacts

Besides being an enabler technology for cellular biology and regenerative medicine, the project will explore new principles in label-free nanoscopy methodology and initiate innovation jumps in optical instrumentation.