On-Demand Injection of Microfluidic Droplets Based on Three-Dimensional Visual Feedback Control for High Volume Consistency and Precise Additive Concentration.

Abstract

Precise and quantitative fluid addition is essential for maintaining consistency in volume and concentration across various applications including pharmaceuticals, food production, and biochemical research. Microfluidic droplet technology has emerged as a versatile microreactor for manipulating nanoliter- to picoliter-scale droplets, offering advantages such as reduced reagent consumption, faster reactions, and enhanced sensitivity. Among these, microfluidic droplet injection technology has shown promise for precise reagent addition. However, passive droplet injection methods as well as active injection methods driven by pneumatic, electrical, and acoustic forces often suffer from volume deviation due to external disturbance. Additionally, traditional two-dimensional (2D) measurement methods overlook the droplet's three-dimensional (3D) curvature, leading to insufficient data capture and significant measurement errors. This study introduces a novel on-demand microfluidic droplet injection system integrating quantitative phase imaging (QPI) for 3D visualization serving as feedback with a dual-pressure-pulse (DPP) method for fluid actuation. Comparative experiments confirmed that our approach significantly improves injection precision, achieving a coefficient of variation (CV) of 7.03%, which represents a 4.5-fold improvement over passive methods. Dynamic response experiments further verified the system's capability to adapt to target volume changes rapidly, maintaining deviations below 2% across varying conditions. As a proof of concept, the system effectively compensates for initial volume fluctuations, ensuring consistent final droplet volumes and enabling controlled isoconcentration of selenium-containing droplets, with deviations of 1.17% and 2.5%, respectively. These findings showcase the system's potential for applications requiring stringent control of volume and concentration, such as single-cell analysis, enzyme kinetics, drug delivery, and food production.