Motivation

Precise single-cell dispensing is critical for advancements in biomedical technology, personalized medicine, and biotechnology. “On-demand” precision-placement of individual cells is expected to enable the cell-by-cell assembly of microstructures within bioprinted organs, and facilitate applications such as cell-level drug screening in oncology. Both fields aim to provide significant societal and economic benefits.

Addressed Problems

Current single-cell bioprinting methods face limitations in cell isolation, cell-dispensing rate, precision placement, and cell-viability. These challenges hinder the effective application and widespread adaption of single-cell technologies in the abovementioned fields. From the deficits in current methods, five minimum requirements for cell-by-cell bioprinters have been derived, and summarized under the acronym “ORCAS”.

Proposed Novel Solution

A new cell-printing paradigm, termed “TrapJet” is proposed that combines microfluidic cell-traps with thermal “drop-on-demand” printing methods to fulfill the five ORCAS criteria simultaneously for the first time. The TrapJet concept aims to significantly increase single-cell deposition-rates and resolution while being scalable and adaptable for various cell-types and applications.

Results

In the current “proof-of-concept” configuration, TrapJet already demonstrates a significant increase in print-rates with respect to existing technologies. The array-based design provides a simple method to upscale print-rates. The capability for precision placement at single-cell resolution, with direct contact between individually deposited cells, was demonstrated. Post-printing cell-viability over at least 24 h was shown via the formation of self-assembled “proto-spheroid”. Fundamental fulfillment of all five ORCAS criteria for single-cell printing was confirmed. A patent-application covering the key elements of TrapJet technology was submitted in July 2023 and disclosed to the public in October 2024.

Outlook

It is proposed that ongoing optimization of TrapJet will further enhance dispensing-rate, making it a viable solution for high-precision additive biomanufacturing. Various additional applications across the biomedical spectrum are accessible without requiring significant modification of current TrapJet technology. Challenges regarding robust cell-supply, trap refill-rate increase, automated cell detection, and general process-automation remain, and should be systematically addressed. In order to unlock TrapJet’s full potential over the next decade, scaling methods from inkjet-printing must be implemented and early integration into future 4D-hybrid-bioprinters ensured.