On-chip rapid drug screening of leukemia cells by acoustic streaming.

ABSTRACT

Rapid and personalized single-cell drug screening testing plays an essential role in acute myeloid leukemia drug combination chemotherapy. Conventional chemotherapeutic drug screening is a time-consuming process because of the natural resistance of cell membranes to drugs, and there are still great challenges related to using technologies that change membrane permeability such as sonoporation in high-throughput and precise single-cell drug screening with minimal damage. In this study, we proposed an acoustic streaming-based non-invasive single-cell drug screening acceleration method, using high-frequency acoustic waves (>10 MHz) in a concentration gradient microfluidic device. High-frequency acoustics leads to increased difficulties in inducing cavitation and generates acoustic streaming around each single cell. Therefore, single-cell membrane permeability is non-invasively increased by the acoustic pressure and acoustic streaming-induced shear force, which significantly improves the drug uptake process. In the experiment, single human myeloid leukemia mononuclear (THP-1) cells were trapped by triangle cell traps in concentration gradient chips with different cytarabine (Ara-C) drug concentrations. Due to this dual acoustic effect, the drugs affect cell viability in less than 30 min, which is faster than traditional methods (usually more than 24 h). This dual acoustic effect-based drug delivery strategy has the potential to save time and reduce the cost of drug screening, when combined with microfluidic technology for multi-concentration drug screening. This strategy offers enormous potential for use in multiple drug screening or efficient drug combination screening in individualized/personalized treatments, which can greatly improve efficiency and reduce costs.