Large-Area Electronics-Enabled High-Resolution Digital Microfluidics for Parallel Single-Cell Manipulation

Abstract

Large-area electronics as switching elements are an ideal option for electrode-array-based digital microfluidics. With support of highly scalable thin-film semiconductor technology, high-resolution digital droplets (diameter around 100 μm) containing single-cell samples can be manipulated freely on a two-dimensional plane with programmable addressing logic. In addition, single-cell generation and manipulation as foundations for single-cell research demand ease of operation, multifunctionality, and accurate tools. In this work, we reported an active-matrix digital microfluidic platform for single-cell generation and manipulation. The active device contained 26,368 electrodes that could be independently addressed to perform parallel and simultaneous droplet generation and achieved single-cell manipulation. We demonstrate a high-resolution digital droplet generation with a droplet volume limit of 500 pL and show the continuous and stable movement of droplet-contained cells for over 1 h. Furthermore, the success rate of single droplet formation was higher than 98%, generating tens of single cells within 10 s. In addition, a pristine single-cell generation rate of 29% was achieved without further selection procedures, and the droplets containing single cells could then be tested for on-chip cell culturing. After 20 h of culturing, about 12.5% of the single cells showed cell proliferation.

Microfluidics: a concise review of the history, principles, design, applications, and future outlook

“…50 For instance, integrating microfluidics with other technologies such as nanotechnology, optics, and electronics has enabled the creation of advanced microfluidic devices with novel functionalities, broadening their applications in areas such as biomedicine, environmental monitoring, and material science. 248,249…”

“…Another example is the integration of microfluidics with electronics for the development of lab-on-a-chip devices, combining microfluidic channels with electronic sensors and circuits for on-chip analysis of samples, with potential applications in a wide range of fields. 249…”

Open Thermal Control System for Stable Polymerase Chain Reaction on a Digital Microfluidic Chip

“…However, with the development of the digital microfluidic technology, the number of electrodes has been further increased to achieve higher parallel processing capabilities. In our previous work, the number of electrodes in a chip was 4096, with a single droplet volume of 10 nL. , Existing temperature control methods cannot meet the requirements of high-throughput DMF chips, especially for scenarios such as droplet digital PCR and single-cell genomics that require temperature control for a large number of droplets. , These scenarios require the consideration of the planar and vertical temperature distribution inside the chip, which has not been previously studied. Therefore, in DMF technology, an open thermal control system that ensures precise temperature control over a wide range is desirable.…”

Smart Droplet Microfluidic System for Single-Cell Selective Lysis and Real-Time Sorting Based on Microinjection and Image Recognition

“…Due to its merits of precision, throughput, compatibility, independence, and lack of contamination, microfluidics, especially droplet microfluidics, − is becoming a powerful tool for single-cell lysis . According to the detailed principle, single-cell lysis methods based on microfluidics can be classified as physical and chemical protocols .…”