Review Article

Latest Updates on the Advancement of Polymer-Based Biomicroelectromechanical Systems for Animal Cell Studies

Table 7

Recent BioMEMS platforms for cell culture including the type of the platform, the main components, the fabrication strategy, the mechanism of operation, and the specifics of each platform.

BioMEMS platformMain componentsFabrication strategyMechanism of operationSpecificsRefs.

Indirect temperature measurement LOCHeating system Temperature sensor plate
PDMS chamber Electrodes
Soft lithographyThe PI control system implemented porous sensors to detect the temperature of the cell culture wells and to generate a response from the closed-loop temperature control system.The platform enables temperature control inside and outside the culture system.[81]
Microheater chip for cell cultureMicroheater
Culture chambers
Electrical probes
Soft lithography and laser direct-write methodsA precise square voltage pulse was applied to the electrical probes in order to generate a heating response from the thermal stimulator.The device supports a wide range of temperatures (37-100°C).[80]
μRespirometer LOCPS matrix
Glass wafer
Microsensor film
DRIE, powder blasting, and UV excitation processesμRespirometer determined the OCR of mammalian cells. The film was integrated into a closed microfluidic chip made of oxygen-impermeable materials.The integrated device allowed continuous fluorescent measurement over 12 hours.[84]
Butterfly-shaped microchipMain channel
Test channel
Fluid reservoir
Standard photolithographyThe main channel width was constant at some places and increased linearly at other regions. The test channels were all positioned at different distances from each other relative to the main channel. The device was used to determine whether there was a distance-dependent interaction between a cell type and a factor.The device was compatible with different cell types and mixtures.[98]
Long-term on-chip cultureFive inlets
Channels
3D printed holder
Photolithography and wet etchingThe culture chamber was located at the center of the device surrounded by two porous hydrogel walls, which provided the nutrients and gases from neighboring channels.The device required no external equipment and provided no shear stress on the cells.[82]
LEGO inspired modular microfluidicThree building blocksConventional lithography on a soft lithography moldThe building blocks could be interlocked via tongue and groove connections and by an interference fit vertical connections. To assemble the double-layer blocks, the microwells were attached to their respective tubing, coupled and hollowed to form an O-ring-free sealed microfluidic system.The device is stiff enough to allow manual coupling of the pieces, and yet, its deformability accommodates the interferences.[75]
Gelatin-based microfluidic cell culture chipPMMA
PDMS
Glass
NOA
GEL-D gelatin film
Soft lithographyThe culture chambers were sealed with their respective GEL-D gelatin film which allowed materials of different natures (PMMA, PDMS, and glass) to be attached to each other and interact with cells.The chips were found to be resistant to pressure (up to 0.7 MPa) and exposure to organic solvent, as well as temperature (up to 70°C)[76]
Multilayered-architecture microfluidic arrayPneumatic layers
Porous membranes
3D culture layer
Fluidic layers
Conventional lithography and soft lithographyThe porous membrane allowed the cell interaction with either different drugs individually or simultaneously due to the incorporated top and bottom valves.The device enables dual drug testing on the same cell culture chamber and is suitable for scaled-up drug testing.[77]
Closed microfluidic cell culture systemBattery
Peristaltic pump
Microchannel (PDMS, SJI-001)
Reservoir
Conventional lithography and soft lithographyCells seeded inside the microchannel were cultured for long periods with a controlled flow rate due to the peristatic pump.SJI-001 was used at the bottom of the microchannel, which improved the overall cell adhesion rate in comparison to the conventional counterpart.[78]
Microdroplet-based microfluidic system4 inlets
Mixing area
Outlet
PMMA laser engraving, drill pressingDouble-layered microdroplets were generated by hydrodynamic focusing, and flows were driven by gravity.Most cells remained undifferentiated, with slight lymphoid and myeloid exceptions.[86]
PDMS-PDA treated microfluidic deviceInlet
Outlet
Microchannel (PDMS, PDA)
Soft lithography and PDA coatingThe culture microchannel had a PDA and a collagen coat in order to improve cell attachment. PDA interacts with the amine groups and covalently binds them into the PDMS surface.The strategy improved cell attachment and stability.[85]

DRIE: deep reactive ion etching; LOC: Lab-on-a-chip; NOA: Norland optical adhesive; OCR: oxygen consumption rate; PDMS: polydimethyl siloxane; PMMA: poly(methyl methacrylate); PI: proportional-integral; GEL: Reversible gelatin-based; 3D: three-dimensional; PDA: polydopamine.