A Microfluidic Concentration Gradient Maker with Tunable Concentration Profiles by Changing Feed Flow Rate Ratios

Abstract

Microfluidic chips—in which chemical or biological fluid samples are mixed into linear or nonlinear concentration distribution profiles—have generated enormous enthusiasm of their ability to develop patterns for drug release and their potential toxicology applications. These microfluidic devices have untapped potential for varying concentration patterns by the use of one single device or by easy-to-operate procedures. To address this challenge, we developed a soft-lithography-fabricated microfluidic platform that enabled one single device to be used as a concentration maker, which could generate linear, bell-type, or even S-type concentration profiles by tuning the feed flow rate ratios of each independent inlet. Here, we present an FFRR (feed flow rate ratio) adjustment approach to generate tens of types of concentration gradient profiles with one single device. To demonstrate the advantages of this approach, we used a Christmas-tree-like microfluidic chip as the demo. Its performance was analyzed using numerical simulation models and experimental investigations, and it showed an excellent time response (~10 s). With on-demand flow rate ratios, the FFRR microfluidic device could be used for many lab-on-a-chip applications where flexible concentration profiles are required for analysis.

Microfluidic dose–response platform to track the dynamics of drug response in single mycobacterial cells

“…Although at present our system does not include components of the immune response, we can create diverse drug exposure patterns, and quantify the dynamics of response of individual cells under clinically relevant infusion patterns. To this aim, target-controlled infusion software systems could be implemented, in conjunction with multiple inlet ports or multi-directional valves, aiming to fine-tune each fluidic input according to in-silico models inferred from human PK parameters [73][74][75] . Spatiotemporal drug gradients could also be achieved by modulated oscillation of the inlet tubing of microfluidic devices.…”

Dynamics of drug response in single mycobacterial cells by microfluidic dose-response assay

“…Although at present our system does not include components of the immune response, we can create diverse drug exposure patterns, and quantify the dynamics of response of individual cells under clinically relevant infusion patterns. To this aim, target-controlled infusion software systems could be implemented, in conjunction with multiple inlet ports or multi-directional valves, aiming to fine-tune each fluidic input according to in-silico models inferred from human PK parameters ( 71–73 ).…”

Automatic Design of Microfluidic Gradient Generators

“…M ICROFLUIDIC concentration gradient generators are important components for biological and chemical research [1,2,3,4,5,6] due to their ability to create spatially resolved concentration values allowing to screen a wide range of concentrations at the same time. Especially tree-shaped gradient generators, comprised of branching, mixing, and recombining channels [7,8,9,10,11,12,13,14,15,16,17,18], are commonly used due to their flexibility in concentration values and their ability to maintain the gradient profile indefinitely [6].…”