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Table 1 Comparison of various techniques available for single cell's stiffness measurement

From: Trends in characterizing single cell's stiffness properties

Technique Cell types Advantages Limitations References
AFM Living neurons (293 T), biological membrane, plant cell, bacteria, fungi, yeast -Wide range of applied forces -Bulky [9]-[13]
-Stiffness map can be generated -Complicated fluid-probe interaction in aqueous environment
-Nano-indentation based on cell membrane displacement -Difficult to be used with non adherent cells
MTC Mouse embryos, endothelial cells, human airway smooth muscle cells, 3 T3 fibroblasts cells -Non invasive -Special procedure to induce cell binding with the beads [14]-[18]
-Free from contamination -Magnetic bead size must be large enough as compared to the sample
MA Neutrophils, chondrocytes, endothelial cell, red blood cells (RBC), HeLa cells, aortic endothelial cells -Cell aspiration can be done without cell bursting -Slow and tedious operation [19]-[22]
-Need an expert for calibration
-Loading pressure can be controlled up to 0.1 Pa -Impossible for big no. of cells
-Fluid loss due to evaporation
-Susceptible to vibration, noise offset and humidity
-Conceptually straightforward
-Time consuming
OT Sickle cell RBC, RBC -Capable of trapping a small object within a defined region -Forces applied is limited to <0.1nN [23]-[25]
-Surpassed the contact problem -Difficult handling and time consuming
-Free from contaminants -Prone to light/optical interference due to poor setting
-High accuracy force measurement -Non uniform stress distribution
-Impossible for big no. of cells
-Exposure to prolong heating
Shear/stretching device Platelets, somatic cell hybrid, astrocytes, motile fish keratocyte, rat cardiac cell, chick embryonic fibroblasts, NIH 3 T3 cell, rat kidney epithelial cells -Cell friendly test -Inappropriate amount of force may cause cell bursting [26]-[34]
-Takes place in fluid environment
-Amount of force needed must be made prior known
-Load cells fixed to the walls of flow chamber
-Challenges to sustain similar chemical environment
MEMS – puller Kidney fibroblasts, BHK-21 fibroblasts, adult myocytes -No need for external actuator -Not suitable to all types of cells [35]-[37]
-Less cost -Limited to one or two degree-of-freedom measurements
-Less complicated -Not suitable to all types of cells
-High sensitivity over broad range
-Small physical size
MEMS – pillar Epithelial cells, cardiac myocytes, Bovine artery pulmonary smooth muscle cells -High sensitivity over broad range -Cell spreading problem [38]-[44]
-Small physical size
-Simpler experimental set up
MEMS – probe Monkey kidney fibroblasts -Less complexity -Cell handling is difficult [45],[46]
-Low cost -Need for expert personnel to operate
-Cell indentation is challenging
Microfluidic-Constricted Geometry RBC, malaria infected RBC, leukaemia cell, monocytic THP-1 cell, neutrophils, MCF-10A cells, MCF-7 cells, MC 3 T3 cells -Widely used to study cell deformation -Prone to clogging [47]-[57]
-Inefficient trapping
-Adjustable dimensions to suit different cell types -Neglecting the effect of membrane rigidity and viscosity
-Variety of geometry structure
Microfluidic-Aspiration Induced Porcine aortic valve interstitial line, human neutrophils, mouse embryo fibroblast, THP-1 cells, RBC -Simple & straightforward concept -Leaking problem [58]-[61]
-Time consuming
-Required high suction pressure
Microfluidic-Fluid Induced HeLa cells, MCF-7 cells, RBC, leukocytes, human lung H1650 cells, yeast cells, -Potential to process sample continuously -Taylor dispersion existence making it hard to track analyte concentrations [62]-[68]
-Can be utilized with other bio-chemical assays
-Limited usage for aliquoting
-Optimized for mixing and separation
-Deform the cell without contact
Microfluidic-Electrically Induced MCF-10A cells, MCF-7 cells, Chinese hamster ovary cells, human promonocytes cells, SiHa cells, ME180 cells, RBC, DNA, L929 cells, 3 T3 fibroblasts cells, DS 19 murine cells, bakers yeast cells -Faster heat dissipation, better resolution, faster separation -Streaming currents which counteract with the external electric [69]-[81]
-Enables the automation and parallelization of tests with reduced amount of samples
-Gas bubble as a result from electrolysis
-Enables pulse free pumping -Hand-held realization is challenging
-High energy consumption and high voltage