Ultra-small tissue-compatible organoid printer for rapid and controllable modeling of respiratory organoids

Current organoid technology faces challenges such as low throughput and limited automation, which leads to inconsistencies in organoid development and hinders clinical applications. The limited ability to handle ultra-small samples greatly restricts the use of organoids in clinical settings. Our research introduces OrgFab, an integrated bioprinter that is able to manipulate ultra-small samples down to 5 μL and accurately print organoids onto 384-well plates. A 10-μL bioink produces around 100 organoid precursors, which is enough for one batch of drug testing. The instrument operates in a fully automated manner, from sample injection to organoid patterning, and the seeding density of the initial cells can be adjusted. High-density microfluidic droplet encapsulation was used to produce respiratory organoids with high fidelity and microenvironment recovery. This method accelerates organoid maturation due to increased paracrine signaling, as shown by RNA sequencing. The instrument promises to automate organoid-based assays for standardized drug discovery and diagnostics.