Review Article

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

Table 5

Recent BioMEMS platforms for cell-cell communication 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 operationSpecificsRef.

Microfluidic device for indirect contact cocultureTwo layers of multiple cell culture chambers
Parallel layer of migration regions
Wet etching methodHuman liver carcinoma cells and human embryonic lung fibroblast cells were introduced into two culture chambers, and culture medium was infused into a third chamber.Indirect coculture with tumor cells was performed in this device. As a result, direct migration and transdifferentiation were observed.[56]
On-chip coculture systemCenter end-closed channels Cell culture chambers MicrochannelsStandard photolithography methodMelanoma cells and immune cells from the spleen of wild type and deficient knockout for interferon regulatory factor 8 mice were cocultured for one week and monitored by fluorescence microscopy and time-lapse recordings.The device monitored the interactions between cancer and immune cells of immune competence vs. immunodeficiency.[59]
Microfluidic device for chemical and physical contactCell culture chambers
Migration microchannel
Human peripheral blood mononuclear cells or alternative mouse splenocytes were loaded into one chamber and treated and untreated tumor cells into another chamber. The cells were carefully monitored by time-lapse recordings.FPR1 promoted interactions between dying cancer cells and leukocytes.[61]
Microfluidic device for tumor simulationCell culture chambers
Hydrogel barriers
Human bladder cancer cells, macrophages, fibroblasts, and HUVECs were cultivated inside the chambers and monitored by inverted microscopy.The device incorporated simulation system for screening of different chemotherapeutic agents.[60]
Synapses on-chipMicrogrooves
Chambers
Perfusion channel
Soft lithography methodRat hippocampal neurons were plated in the two compartments, cultured, and then infected with either a GFP- or RFP-Sindbis virus in order to visualize potential connections.The device incorporated simulation system to access and manipulate synaptic regions.[62]
Axon and glia coculture systemTwo compartments
Central channels
Standard photolithographyNeurons and glial cells were cultured in separate chambers. Only neuronal processes (especially axons) could enter the glial side through the central channels.The device allowed the studying of the signaling pathways between neurons and glia.[64]
Macro-micro-nano systemCell-seeding compartments
Nanochannel array
Two-step photolithography processOsteocyte-like cells and motor neurons were cultured on the device for 7 days and heated from one side. The concentrations of extracellular ATP and ATP receptor were measured to quantify the response of the cells.The device measured the signal response of osteocytes and neurons to heat shock.[97]
Multicompartment neuron-glia coculture platformCircular soma compartment
Satellite axon/glia compartments
Microchannels
Micromilling, hot embossing, and soft lithography methodsDissected primary neuron cells were loaded into the soma compartment. After 14–17 days of culture. When a dense axonal layer inside the axon/glia compartments was formed, oligodendrocyte progenitor cells and astrocytes were loaded on top of the isolated axon layer.The device facilitated the studying of the central nervous system axonal biology and axon–glia interactions.[65]
PDMS chipPDMS chip
Microreactor
100 mesoscale open wells
Microscale deep channels
Soft lithography method and UV lithographyCells were cultured in adjacent wells in the microreactor. Cell-cell communication was possible via the interconnecting channels of neighboring wells.The microstructure system allows both spatially separated cocultivation and specific treatment of cells.[63]
Unidirectional microfluidic chipTwo culture chambers
Two surrounded medium channels
Traditional photolithography and soft lithographyCells were cultured in separate culture chambers, and their respective secretions traveled through the medium channels to the opposing culture chambers.The device facilitated the study of communication and conversion between healthy and cancerous cells.[57]
Two-layer microfluidic devicePDMS layer
Two culture channels
Two media supply channels
Agarose layer
Traditional photolithography, soft lithography, and PDMS replicationBreast cancer cells and human adipose stromal cells were cultured in the inner culture channels while fresh media was supplied by the outer channels. The spacing between the media and the cell channels allowed the delivery of fresh media and cellular crosstalk via passive diffusion.The delivery of fresh media via a separate channel reduced the risk of the cells’ exposure to shear stress.[58]

ATP: adenosine triphosphate; FPR1: formyl peptide receptor 1; HUVECs: human umbilical vein endothelial cells; PDMS: polydimethylsiloxane.