Abstract
Despite the precise controllability of droplet samples in digital microfluidic (DMF) systems, their capability in isolating single cells for long-time culture is still limited: typically, only a few cells can be captured on an electrode. Although fabricating small-sized hydrophilic micropatches on an electrode aids single-cell capture, the actuation voltage for droplet transportation has to be significantly raised, resulting in a shorter lifetime for the DMF chip and a larger risk of damaging the cells. In this work, a DMF system with 3D microstructures engineered on-chip is proposed to form semi-closed micro-wells for efficient single-cell isolation and long-time culture. Our optimum results showed that approximately 20% of the micro-wells over a 30 × 30 array were occupied by isolated single cells. In addition, low-evaporation-temperature oil and surfactant aided the system in achieving a low droplet actuation voltage of 36V, which was 4 times lower than the typical 150 V, minimizing the potential damage to the cells in the droplets and to the DMF chip. To exemplify the technological advances, drug sensitivity tests were run in our DMF system to investigate the cell response of breast cancer cells (MDA-MB-231) and breast normal cells (MCF-10A) to a widely used chemotherapeutic drug, Cisplatin (Cis). The results on-chip were consistent with those screened in conventional 96-well plates. This novel, simple and robust single-cell trapping method has great potential in biological research at the single cell level.
Highlights
Cells are analyzed based on the responses of a large population cultured in Petri dishes or well plates[1,2]
We present a digital microfluidics (DMF) system (Fig. 1) for single-cell culture with innovative micropatterned arrays constructed by 3D microstructures fabricated on a DMF chip to trap single cells and to prevent the trapped cells from aggregating during a long-time cell culture
For digital microfluidics (DMF), individual droplets are manipulated on an array of electrodes
Summary
Cells are analyzed based on the responses of a large population cultured in Petri dishes or well plates[1,2]. Single-cell culture and analysis remain in high demand for a full understanding of the cell-to-cell variability and for precision medicine. Microfluidics has emerged as the most promising platform for single-cell analysis due to its characteristics in handling small volumes of samples. Single-cell culture has been investigated with channel microfluidics with one or no cells in each droplet for precise cell identification[3,4,5,6]. Microfluidic devices integrated with dielectrophoresis (DEP)[7,8], optical tweezers[9,10,11], or acoustic waves[12,13] are powerful in trapping and manipulating single cells. Among the reported single-cell capture methods, microwell arrays fabricated in the flow channel have the highest single-cell capture efficiency
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