Fluidic-manipulation-enabled multiplexed dose delivery of RONS by a CAP chip for dose optimization enhancement.

The plasma-derived reactive oxygen and nitrogen species (RONS) enable cold atmospheric plasma (CAP) to combat cancer and infectious wounds. Achieving therapeutic outcomes with CAP necessitates precise treatment doses. Current CAP devices are constrained by their capability of delivering a single dose to a single sample, limiting dose optimization. We propose a novel "one exposure, multiple-dose delivery" strategy by programming gas flows. This approach facilitates efficient screening of optimal CAP dose by distributing feed gas through boundary-conditioned transport channels to generate multiple, flux-varied gas streams, which ignite plasmas with diverse chemical compositions and dose gradients across samples. Our developed demonstration device, capable of administering three doses to sixteen samples, significantly reduces experimental complexity, particularly when handling large candidate doses or samples for treatment. Leveraging multiplexed treatment, we capably optimize the CAP dose to effectively eradicate the liver cancer cell line of Huh7 and bacteria of S. aureus within one exposure. Furthermore, we find manipulating gas flow velocities allows targeted generation of short-lived species. This approach disentangles the roles of short-lived and long-lived RONS in therapeutic applications, offering critical insights into their bio-functional mechanisms. The concept of multiplexed dose treatment with fluidic manipulation promises to catalyze the development of high-efficiency CAP devices and advance research in CAP-based therapies.