Vision-Based 40-nm-Accuracy Liquid Level Detection Compliant With Micromanipulation

Recent efforts in single-cell research call for precise liquid level detection (LLD) for end-effectors to manipulate small volume of liquid samples such as nano- to pico-liter droplets. Existing LLD methods, however, are yet satisfactory for such delicate micromanipulation tasks. This article presents a vision-based contact type LLD method, which adopts the hardware settings normally used in typical micromanipulation scenarios. The detection principle is based on the generation of patterned ripples when the end-effector (e.g., glass micropipette), that is being vibrated, moves to get contact with the liquid surface. Through the microscopic imaging system in micromanipulation, the image frames of patterned ripples such as concentric circles are recorded, from which the wavelength is extracted to determine the contact moment. The vision-based LLD method was cross-validated by the electrical impedance-based method. Experiments revealed that the best detection accuracy was 40 nm, only limited by the micromanipulator's positioning resolution. Moreover, the method was robust to various micromanipulation settings, such as illumination intensity, microscopy magnification, exposure time, and focal plane. As a demonstration, this method was successful in detecting the surface of droplets with a volume as low as 450 pL for different liquids. Given its generality, this method is expected to suit many scenarios involving liquid handling tasks in micromanipulation and industry.