High-Definition Single-Cell Printing: Cell-by-Cell Fabrication of Biological Structures

Abstract

Bioprinting is a powerful technology with the potential to transform medical device manufacturing, organ replacement, and the treatment of diseases and physiologic malformations. However, current bioprinters are unable to reliably print the fundamental unit of all living things, single cells. A high-definition single-cell printing, a novel microfluidic technology, is presented here that can accurately print single cells from a mixture of multiple candidates. The bioprinter employs a highly miniaturized microfluidic sorter to deterministically select single cells of interest for printing, achieving an accuracy of ≈10 µm and speed of ≈100 Hz. This approach is demonstrated by fabricating intricate cell patterns with pre-defined features through selective single-cell printing. The approach is used to synthesize well-defined spheroids with controlled composition and morphology. The speed, accuracy, and flexibility of the approach will advance bioprinting to enable new studies in organoid science, tissue engineering, and spatially targeted cell therapies.

Keywords: bioprinting; droplet microfluidics; fluorescence-activated cell sorting; single-cell printing; spheroids.