2-layer based microfluidic concentration generator by hybrid   serial and volumetric dilutions.
We present a 2-layer based microfluidic concentration generator by a hybrid of a serial and a volumetric dilution for dose-response experiments in drug screening. The hybrid dilution method using 2-layer based microfluidic network significantly reduces the total number of cascaded serial dilution stages. The proposed strategy is capable of generating a large number of universal stepwise monotonic concentrations with a wide range of logarithmic and linear scales. We have studied an equivalent electrical circuit to that of the 2-layer based microfluidic network, where the only variable parameter is channel length. We have designed a microfluidic dilution generator simultaneously covering 14 doses with a combination of 4-order logarithmic and 4-point linear concentrations. The design has been verified by a commercial circuit analysis software (e.g., P-Spice) for the electrical circuit analysis and a computational fluid dynamics software (e.g., CFD-ACE+) for the microfluidic circuit analysis. As a real-life application of the proposed dilution generator, we have successfully performed a dose-response experiment using MCF-7 human breast cancer cells. We expect that the proposed dilution method will be useful to study not only high throughput drug screening but also optimization in biology, chemistry, medicine, and material sciences.
Lee
Kangsun
K
SMALL, Nanobio Sensors and MicroActuators LearningLaboratory) Department of Electrical Engineering, University at Buffalo, The State University of New ,Buffalo, NY 14260, USA.
Kim
Choong
C
Kim
Youngeun
Y
Jung
Keunhui
K
Ahn
Byungwook
B
Kang
Ji Yoon
JY
Oh
Kwang W
KW
D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation*; D006801:Humans; D007201:Indicator Dilution Techniques / Q000295:instrumentation*; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods*; D044085:Microfluidics / Q000295:instrumentation* / Q000379:methods; D012984:Software