Review Article

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

Table 6

Recent BioMEMS platforms for cell differentiation and identification 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.

μIFCAu and Cr electrodesConventional soft lithography techniqueA current between the external electrodes was generated by an AC signal. In the absence of particles, the output current was zero. In the presence of the particle, however, the positive output voltage increased. When the particle reached the second electrode, the negative output voltage was recorded.Differentiation was possible even when the cells had similar sizes.[66]
Pump-free microfluidic platformPDMS-based microfluidic device
Micropillars
Valve control
Soft lithography and DRIEA pump-free perfusion system was used for long-term differentiation. A passive pumping system was implemented to control medium perfusion in a constant flow rate.The differentiation was achieved within 14 days. The device had a derivation efficiency of 92%.[67]
Frequency shift-based POC deviceFPW sensor
Comb-like IDT electrodes
Five photolithographic steps based on photomask-setOscillations (23-30 MHz) were introduced to the device and caused the biomolecules to bind to the surface. The attached cells to the surface produced a mass gain.The device binds only to one type of chemokine and repels others.[68]
Electrical impedance spectroscopy-based LOCSilicon wafers and PDMSPhotolithography and anisotropic etchingImpedance measurements were done at 750 kHz and 10 MHz. Since the cells were of different sizes, the detected values depended on the size of cells. Finally, opacity could be used to differentiate cell lines.This noninvasive device has an effectiveness of 93.2%. The method requires no functionalization or cell labeling.[69]
Impedance measurement-based microfluidic devicePDMS
Microchannels
Bypass channels
Coplanar electrodes
Soft lithography and lift-offThe first path in this device was a trap while the second path was a bypass channel. When the trap was empty, a cell would be driven into the trap. Once the trap was occupied by a cell, the flow-through path would block. Therefore, the next cell would be driven into the bypass channel and enter the next available trap.The device could monitor dynamic changes in electrical properties of individual cells over long periods of time.[91]
Single-cell detection sensorExternal magnet Electrodes Microcoulter counter
Microfluidic chip
Standard soft lithographyThe sensor was able to detect single cells due to their magnetic properties. Three electrodes were used and divided the straight microchannels into two consecutive stage microcoulter. When the cells passed through the microcoulter, each cell generated a voltage pulse and by using the magnetic beads, the target cells were identified.The device identifies and counts cells in situ while measuring the size of each cell individually.[70]
Impedance-based CTC detectorPDMS
Syringe pump
Sensors
Planar electrodes
Photolithography and lift-offThe “off-chip” device had an embedded pair of planar electrodes. The impedance was obtained in the surrounding of the medium. When the CTC was detected, an impedance peak was obtained. When the “on-chip” device detected a CTC in the constriction channel, a peak was deviated from a constant baseline.Differentiation was achieved with 90% of success. The system has the potential for detecting different types of cancer.[71]
ISCRSPDMS
ESI-QTOF-MS
Syringe pump
Standard soft lithographyThe target cell was captured due to the probe’s adjustment.The accuracy of the classification was 91.8%.[72]
Photostimulation-based LOCPDMS
Gold nanorods
Standard soft lithographyGNRs were added into the cell buffer, and photostimulation was performed. Subsequently, the solution of suspended cells and oil was injected into the chip, and the cells created a single-cell laminar flow. Lastly, the cells were delivered into a petri dish for culture and analysis.The necrosis of apoptosis can be controlled by the laser focusing.[73]

AC: alternating current; : cell’s resistance; CTCs: circulating tumor cells; Cr: chromium; CMOS: complementary metal-oxide-semiconductor; DRIE: deep reactive ion etching; ESI-QTOF-MS: electrospray quadrupole time of flight mass spectrometer; FPW: flexural plate-wave; Au: gold; GNR: gold nanorods; IDT: interdigital transducer; ISCRS: in situ single-cell recognition system; LOC: Lab-on-a-chip; μIFC: microfluidic-based impedance flow cytometer; PDMS: polydimethyl siloxane; POC: point-of-care.