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BioMEMS platform | Main components | Fabrication strategy | Mechanism of operation | Specifics | Ref. |
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Centrifugal hydrodynamic microfluidic chip | Cell chamber array Hydrodynamic-assisted single-cell traps | Standard soft lithography methods | Individual cells were hydrodynamically trapped and relocated into cell chambers by centrifugation of transient storage. Subsequently, a second cell could be captured and trapped in the structure of the device. | By this selective manipulation, the device could trap three or more single cells in one cell chamber. Moreover, the design gave more available spatial space to the cells and without chamber-chamber crosstalk. | [44] |
Hydrodynamic microfluidic chip | Hydrodynamic trap Oil-isolated microchambers | Cells flowed by hydrostatic pressure, and the corresponding traps were occupied. Subsequently, residual cells were washed away, and a different cell suspension was added sequentially. | High efficiency and single-cell accuracy were offered in this device with minimize chance of cross-contamination. | [45] |
Mechanical parylene slide system | PRF Tweezers Glass substrate SU-8 comb layer PDMS box PDMS cover Syringe pump | Tweezers were used to control the trapping area, where PFR on the comb layer was slide to open positions and cells were trapped along the PFR. Subsequently, another cell could be trapped through the same strategy. | The mechanism allowed the control of the amount and order of lined-up cells; however, the cell pairing system depended on wettability of the surfaces. | [46] |
Microfluidic deformability-based device | PDMS hydrodynamic traps Flow-through channel Syringe pumps | The cells were captured in the single-cell traps by passive hydrodynamics and pipetting. Once saturation was reached, additional cells traveled through the trap with an increased flow. Thus, the second load of cells were introduced to the device and were passively transferred into the larger traps with the captured cells. | Sequential trapping and pairing of cells with similar and diverse sizes were possible. In this platform, the cell fusion was achieved using biological, chemical, and physical biological, chemical, and physical stimuli. | [47] |
Droplet-based microfluidic platform | Sorting chip Collection chip Electroosmotic pump Syringe pumps | Before encapsulation, each cell type was stained with different fluorescent dyes. Afterward, emulsions were injected into the device and a refilling pump was used to withdraw droplets that did not trigger sorting. The positive droplets were collected into the chip, and trapping was monitored. | The device mimics a niche environment enabling pairing and cell-cell interactions at the single-cell level. It does not require specific solutions for cells of different sizes. | [48] |
Multifunction-integrated microfluidic device | IDA electrodes Microwells | Standard lift-off process, soft lithography technique, and mold-replica modeling | P-DEP was applied to attract two cells into the trenches. n-DEP force was then activated to achieve cell pairing. | Either electrical or chemical stimuli can be used for cell fusion allowing flexibility and multi-fusion. | [50] |
Droplet-based multifunctional microfluidic platform | Pneumatic microvalve Droplet trap chamber Lateral bypass channels | Multilayer soft lithography using PDMS | The array operates in a FIFO manner. The generated droplets were carried by the continuous oil phase into the FIFO storage unit and sequentially captured in the traps to form a library of immobilized droplets. After filling the trap array, selected droplets were moved to the merging chamber, where controlled droplet fusion was induced. | The entire procedure was accomplished in several minutes. | [51] |
Droplet microfluidic platform | Droplet microfluidic system 3D electrodes Microfluidic channels Droplet cultivation channel | 2PP microfabrication Multilayer soft lithography using PDMS | Vertical droplet cultivation was reflowed into a planar droplet reflow channel remaining tightly packed. Subsequently, the train of water-in-oil emulsion droplets flowed into the aqueous flow, and the carrier oil was cleaved into the first train of droplets which generated a second water-in-oil emulsion droplet, resulting in their pairing. | Droplets had the capacity to encapsulate cells from a large library to generate droplet libraries, while the paired cells remained closely connected. | [49] |
HL-Chip | Microwell platform Dual-well HL-Chip | Soft lithography | Objects were precisely positioned and loaded into the array and briefly centrifuged until the occupancy was achieved. The dual-well structure contributed to pairing. | The device permitted design arrays of defined cell/object combinations for different analysis and material retrieval. | [52] |
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