Session: 14-10-01: Micro/Nanofluidics 2025 I

Paper Number: 172546

High-Throughput and Pump-Free Droplet Generation via Integrated Microfluidic Pipette Tips 

Droplet-based microfluidics are transforming biomedical and life sciences by enabling high-throughput, quantitative analysis of molecules and cells while minimizing reagent consumption. Despite these advantages, the widespread adoption of droplet microfluidics in biological and clinical settings has been hindered by the complexity of device fabrication—which often relies on advanced nanofabrication techniques—and the need for external pumps and precisely controlled fluidic systems. To overcome these barriers, we introduce the Integrated Microfluidic Pipette Tip (IMPTip), a simple and robust solution for generating uniform water-in-oil droplets as small as 30 µm in diameter, without requiring pumps and intricate microfluidic setups.

The IMPTip assembles a microfluidic adapter chip with a 24-nozzle array onto a standard pipette tip, enabling the generation of over 1,000 droplets per pipette stroke. The adapter chip features ultra-shallow nozzles with a height of 14 µm, and its mold is fabricated using stereolithography with a single 25 µm-thick resin layer. Optimizing resin overcuring parameters enables reliable fabrication of nozzle dimensions smaller than the nominal spatial resolution of the 3D printer. To guide the IMPTip design, a volume-of-fluid computational fluid dynamics (CFD) free-energy analysis is conducted. Furthermore, two novel 3D geometries—winged and wide-throat designs—are investigated to enhance droplet size uniformity.

The IMPTip can be easily assembled using a plug-and-play microfluidic adapter module compatible with standard 20 µL, 200 µL, and 1000 µL pipette tips. Microfluidic adapters with varying channel heights (16–271 µm), wedge angles (15°–75°), and -aspect ratios (2-10) are systematically investigated. The IMPTip can be rapidly prototyped within 10 hours, including stereolithographic printing of the adapter mold, soft lithography for PDMS replication, and final assembly of the adapter with the pipette tip. Once filled with aqueous samples, the pipette tip is inserted into the adapter, enabling direct droplet generation via a step-emulsification process, in which interfacial tension—induced by the nozzle geometry changes—causes the fluid to break into uniform droplets.

Volume-of-fluid CFD simulations were first conducted to optimize the dimensions and cross-sectional geometries of the microfluidic adapter chip by analyzing variations in interfacial free energy. Based on these optimized designs, droplets were experimentally generated using IMPTips, with the droplet formation process recorded under an inverted microscope for subsequent analysis of droplet diameter and coefficient of variation (CV) to evaluate uniformity. Monodisperse water-in-oil droplets (CV < 4%) were consistently produced across a wide range of flow rates (0.2–50 µL/min) using a single channel with a height of 100 µm. Droplet diameter decreased linearly from 794 µm to 30 µm as the nozzle height was reduced from 271 µm to 16 µm. Increasing the nozzle wedge angle to 75° resulted in a 27% reduction in droplet size, suggesting that steeper nozzle expansions lower the energetic barrier for neck formation during droplet breakup. In addition, 3D nozzle geometries with winged or wide-throat profiles generated droplets up to 30% smaller than those formed in conventional rectangular channels at the same flow rate (0.5 µL/min), highlighting the critical role of 3D design in controlling droplet size. Finally, IMPTips equipped with a 24-nozzle array demonstrated the capability to generate over 1,000 monodisperse water-in-oil droplets (CV < 4%) in a single 20 µL pipette stroke, enabling high-throughput droplet production.

In summary, this paper presents a pump-free, rapidly prototyped IMPTip capable of efficient, high-throughput droplet generation. The CFD simulation results closely match the experimental observations in terms of neck formation and breakup dynamics during droplet generation. By eliminating the need for external pumps, continuous-phase oil setups, and time-consuming flow rate adjustments, the IMPTip offers unprecedented simplicity and ease of use for producing uniform droplets. This approach has the potential to greatly expand access to droplet microfluidics for researchers in biological and clinical fields, streamlining workflows for applications such as single-cell analysis, digital PCR, drug screening, and disease diagnostics.

Presenting Author: Dehang Zhu University of Pennsylvania

Presenting Author Biography: Dehang Zhu is currently an M.S. student at the University of Pennsylvania. He received his B.S. degree in Applied Chemistry from Dalian University of Technology. His research interests include microfluidics, lab-on-a-chip, and BioMEMS.

Authors:

Dehang Zhu University of Pennsylvania
Feiyu Wang University of Pennsylvania
Wenyi Huang University of Pennsylvania
Kayla Fox University of Pennsylvania
Shujie Yang University of Pennsylvania