Label-Free On-Chip Selective Extraction of Cell-Aggregate-Laden Microcapsules from Oil into Aqueous Solution with Optical Sensor and Dielectrophoresis

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.