No abstract

Physicochemical conditions play a key role in the development of biofilm removal strategies. This study presents an integrated, double-layer, high-throughput microfluidic chip for real-time screening of the combined effect of antibiotic concentration and fluid shear stress (FSS) on biofilms. Biofilms of Escherichia coli LF82 and Pseudomonas aeruginosa were tested against gentamicin and streptomycin to examine the time dependent effects of concentration and FSS on the integrity of the biofilm. A MatLab image analysis method was developed to measure the bacterial surface coverage and total fluorescent intensity of the biofilms before and after each treatment. The chip consists of two layers. The top layer contains the concentration gradient generator (CGG) capable of diluting the input drug linearly into four concentrations. The bottom layer contains four expanding FSS chambers imposing three different FSSs on cultured biofilms. As a result, 12 combinatorial states of concentration and FSS can be investigated on the biofilm simultaneously. Our proof-of-concept study revealed that the reduction of E. coli biofilms was directly dependent upon both antibacterial dose and shear intensity, whereas the P. aeruginosa biofilms were not impacted as significantly. This confirmed that the effectiveness of biofilm removal is dependent on bacterial species and the environment. Our experimental system could be used to investigate the physicochemical responses of other biofilms or to assess the effectiveness of biofilm removal methods.

Microfluidic lab-on-chip devices are widely being developed for chemical and biological studies. One of the most commonly used types of these chips is perfusion microwells for culturing multicellular spheroids. The main challenge in such systems is the formation of substantial necrotic and quiescent zones within the cultured spheroids. Herein, we propose a novel acoustofluidic integrated platform to tackle this bottleneck problem. It will be shown numerically that such an approach is a potential candidate to be implemented to enhance cell viability and shrinks necrotic and quiescent zones without the need to increase the flow rate, leading to a significant reduction in costly reagents’ consumption in conventional spheroid-on-a-chip platforms. Proof-of-concept, designing procedures and numerical simulation are discussed in detail. Additionally, the effects of acoustic and hydrodynamic parameters on the cultured cells are investigated. The results show that by increasing acoustic boundary displacement amplitude (d0), the spheroid’s proliferating zone enlarges greatly. Moreover, it is shown that by implementing d0= 0.5 nm, the required flow rate to maintain the necrotic zone below 13% will be decreased 12 times compared to non-acoustic chips.

Microfluidic lab-on-chip devices are widely being developed for chemical and biological studies. One of the most commonly used types of these chips is perfusion microwells for culturing multicellular spheroids. The main challenge in such systems is the formation of substantial necrotic and hypoxic zones within the cultured spheroids. Herein, we propose a novel acoustofluidic integrated platform to tackle this bottleneck problem. We show that such an approach enhances cell viability and shrinks necrotic and hypoxic zones in these spheroid-on-a-chip platforms without the need to increase the flow rate, leading to a significant reduction in costly reagents' consumption. Proof-of-concept, designing procedures, and finite element numerical simulation are discussed in details. Also, the effects of acoustic and hydrodynamic parameters on the cultured cells are investigated. The results show that by increasing acoustic boundary displacement amplitude (d0), the spheroid’s proliferating zone enlarges greatly. Moreover, it is shown that by implementing d0=0.5 nm, the required flow rate to maintain the necrotic zone below 13% will be decreased 12 times compared to non-acoustic chips.