A digital microfluidic system with 3D microstructures for single-cell culture

• Published in: Microsystems & nanoengineering Vol. 6; no. 1; p. 6
• Main Authors: Zhai, Jiao, Li, Haoran, Wong, Ada Hang-Heng, Dong, Cheng, Yi, Shuhong, Jia, Yanwei, Mak, Pui-In, Deng, Chu-Xia, Martins, Rui P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.01.2020; Springer Nature B.V
• Subjects: 639/166; 639/166/987; Actuation; Biotechnology; Breast cancer; Cell culture; Cisplatin; Controllability; Damage; Droplets; Electrodes; Engineering; Evaporation; Life span; Microfluidics; Surfactants; Transportation; Voltage
• ISSN: 2055-7434; 2096-1030; 2055-7434
• DOI: 10.1038/s41378-019-0109-7

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. Microfluidics: Use of 3D microstructure enables single-cell culture A novel microfluidic device enables researchers to isolate and culture single cells for use in drug testing and other experiments. To date, the high voltages required to capture cells on electrodes of a digital microfluidic (DMF) device have led to a reduced lifespan for the device and potentially damaged the cells. A team led by Yanwei Jia of the University of Macau overcame this by incorporating 3D microstructures into a DMF chip. This constrains the shape of cell culture droplets to isolate and capture single cells. With the use of low evaporation temperature oil and a surfactant, the system enabled them to use one quarter of the voltage of other designs for droplet transportation. The ability to isolate and culture individual cells will be of great value in addressing biological questions at the single-cell level.