Durability of the bubble-jet sorter enables high performance bio sample isolation

Abstract

Sorting cells while maintaining their viability for further processing or analysis is an essential step in a variety of biological processes ranging from early diagnostics to cell therapy. Sorting techniques such as fluorescence-activated cell sorting (FACS) have evolved considerably and provide standard ways of sorting. Nevertheless, the search for compact, integrated, efficient, and high throughput microfluidic sorting platforms continues due to challenges such as cost, cell viability, and biosafety. In our previous work, we introduced a technology with the potential to become such a platform: the bubble-jet sorter. It is a silicon-based sorter chip relying on cell deflection through micro vapor bubble formation. In this work, we present a new version of the sorter chip that emphasizes durability and continuous sorting operation. To characterize the sorter, we first focus on the technical performance and show a sorter lifetime that repeatedly exceeds 80 million actuation cycles. In addition, we show continuous operation at high firing rates, but also discuss limitations due to heat buildup. In a second step, we present continuous sorting runs of millions of beads and CD3 positive T cells at rates surpassing 1000 sorting events per second, while maintaining high purity (>90%) and recovery (>85%). Dedicated viability tests show that the gentle sorting process maintains cell viability in this closed, aerosol-free device. The remarkable combination of high lifetime, sorting rate, and sorting efficiency, along with the potential for on-chip parallelization show the promise of this technology to meet the growing demand for large-scale sample isolation in drug and immunotherapy development.