Label-Free On-Chip Selective Extraction of Cell-Aggregate-Laden Microcapsules from Oil into Aqueous Solution with...

Microfluidic encapsulation of cells or tissues in biocompatible solidlike hydrogels has wide biomedical applications. However, the microfluidically encapsulated cells/tissues are usually suspended in oil and need to be extracted into aqueous solution for further culture or use. Current extracting techniques are either nonselective for the cell/tissue-laden hydrogel microcapsules or rely on fluorescence labeling of the cells/tissues, which may be undesired for their further culture or use. Here we developed a microelectromechanical system (MEMS) to achieve label-free on-chip selective extraction of cell-aggregate-laden hydrogel microcapsules from oil into aqueous solution. The system includes a microfluidic device, an optical sensor, a dielectrophoretic (DEP) actuator, and microcontrollers. The microfluidic device is for encapsulating cell aggregates in hydrogel microcapsules using the flow-focusing function with microchannels for extracting microcapsules. The optical sensor is to detect the cell aggregates, based on the difference of the optical properties between the cell aggregates and surrounding solution before their encapsulation in hydrogel microcapsules. This strategy is used because the difference in optical property between the cell-aggregate-laden hydrogel microcapsules and empty microcapsules is too small to tell them apart with a commonly used optical sensor. The DEP actuator, which is controlled by the sensor and microcontrollers, is for selectively extracting the targeted hydrogel microcapsules by DEP force. The results indicate this system can achieve selective extraction of cell-aggregate-laden hydrogel microcapsules with ∼100% efficiency without compromising the cell viability, and can improve the purity of the cell-aggregate-laden microcapsules by more than 75 times compared with nonselective extraction.