Objectives

Organoids are 3D organ-like structures constructed in vitro from primary tissues, adult stem cells, embryonic stem cells or human induced pluripotent stem cells (hiPSCs) and exhibit key aspects of the in vivo function of the native organ. The mechanistic understanding of tissue maintenance, injury and repair derived from studying organoids holds an unfulfilled promise for the development of personalized medicine and new drug discovery. The pending delivery on the promise is attributed to the challenge of visualizing and modelling real-time dynamic cellular events in a three-dimensional (3D) tissue-like context of organoid. OrganVision’s multi-disciplinary technology solution will face this precise challenge and help accelerate organoid research toward better disease understanding, therapy design and knowledge discovery. OrganVision will establish its impact through a proof-of-concept on living engineered heart tissues (EHTs) that mimic heart muscle, are pivotal in cardiac therapy design, and extremely challenging to study because of the dynamics of heart beating.

OrganVision envisions to shift the paradigm for organoids from disease or drug-screening models to observable tissue micro-bio-environment for unravelling key physiological and pathological processes in humans. We aspire to enable the exploitation of the most important feature of organoids – life, health, disease, and death unfolding in real-time at sub-cellular and inter-cellular scales in cells and tissues, respectively.

Our ambition is to:

• Overcome the central obstacle that prevents realization of the vision, namely lack of real-time high-resolution label-free imaging technology suitable for organoids;
• Create new opportunities for organoid research and exploit them.

The current practice for imaging organoids employs perturbative and toxic fluorescence techniques with limited photon budget (translating to limited number of images) and trade-offs related to speed, resolution, and penetration. Most studies are therefore done in the form of time separated snapshots of the organoids in steady state, i.e. when disease or drug action has settled. RTI of life processes at various functional scales (inside cells to across the tissue) is difficult in organoids, and currently impossible for highly dynamic and heterogeneous biological systems such as a beating EHT.

Improvement in existing techniques is difficult because the light scattered by the or ganoid creates a large background blur which cannot be removed through advanced instruments or algorithms. OrganVision’s central goal is to develop a revolutionary microscopy technology to videograph the life processes in real-time at cell and tissue scales inside a living organoid without perturbing it through fluorescence markers. OrganVision’s ground-breaking multi-scale imaging technology will exploit the fact that light scattered by the sample encodes the sample’s inherent optical properties, a phenomenon that can be modelled at different scales by different physical models. It will therefore transform scattered light from being a road-block to a fundamental asset. By meeting the seemingly unsurmountable central challenge, OrganVision opens up new opportunities for studying organoids in real time.

We will simultaneously take up the challenges associated with making OrganVision a powerful knowledge discovery tool by undertaking also the following objectives:

• Imparting interpretability to the label-free 3D images acquired using OrganVision imaging technology through virtual staining them
• Developing interesting biological case studies which can exploit the breakthrough imaging technology for deriving unprecedented insight into the life processes of EHTs
• Developing a biotechnology platform for manipulating the environment of EHTs while imaging
• Developing artificial intelligence protocols for analyzing the large volumes of data generated by OrganVision