Article on a new cell culture and imaging platform (JeWell) which can grow, maintain and analyse thousands of artificial organs rapidly in 3D. Written for MBI.

Based on: Automated high-speed 3D imaging of organoid cultures with multi-scale phenotypic quantification; Read here too: https://www.mbi.nus.edu.sg/science-features/the-crown-jewell-of-organoid-imaging/

Organoids are lab-grown cells or tissues that mimic organs. As models of the original organs, they enable scientists to modify and observe organs outside the body. This helps scientists to explore how our anatomy develops, how disease spreads in our body, and if a drug works or causes side effects. For example, heart ‘injury’ models are used to study the regenerative potential of heart muscle cells after they receive damage.

However, growing consistent and reproducible organoids is often difficult, and using organoids with physical variabilities skews the accuracy of their experiments. On top of that, current methods are not sophisticated enough to examine them efficiently in large numbers and in 3D. Thus, to create and check through so many organoids at a time is a great technological challenge.

To overcome this, the lab of Assoc. Prof. Virgile Viasnoff, Research Asst. Prof. Anne Beghin of the SiMBA-Microscopy Core and Dr. Gianluca Grenci of the Microfabrication Core from the Mechanobiology Institute set out to create a one-stop automated platform for growing, imaging and characterising organoids. This was achieved by synergistically combining advanced approaches in producing and studying them — including live and 3D imaging of organoids that is also long-term, high-content and high-speed, as well as the use of artificial intelligence for classifying them. Their invention was detailed in Nature Methods.

Known as the JeWell chip, each chip contains hundreds to thousands of JeWells, which are microscopic, pyramid-shaped chambers. The sample, typically a cell or a collection of them, sits at the bottom of the chamber to be grown (or "cultured") into organoids. Since organoids come in a diversity with unique physical and growth requirements, the shape, size and condition of JeWells can be customised to cater to them accordingly. For example, to grow the vessels that transport bile from the liver, the length of the JeWell can be made longer to house more tubular organoids.

Petri dishes each containing a JeWell chip, which each also contains thousands of “JeWells”

Each JeWell is also outfitted with mirrors on its inner walls, and a light source and a singular detecting lens underneath the sample. They work together as a system to visualise the sample, a method known as “single-objective selective-plane illumination microscopy (soSPIM)”. How SoSPIM works is that each mirror (on a 45° incline) naturally reflects the light beam (approaching from below) at a 90° angle towards the sample. The narrow beam cuts across the sample horizontally, illuminating only a cross-section or a single “plane” of it. The light intersecting the plane is then picked up by the detector. The thickness of the beam, which affects how focused the beam is on the plane, is synchronised to the position of the plane — similar to adjusting the focus of camera to the position of the subject to get the sharpest photo.

How the soSPIM component of JeWell helps to visualise the sample