Trends in characterizing single cell's stiffness properties

Ahmad, Ida Laila; Ahmad, Mohd Ridzuan

doi:10.1186/s40486-014-0008-5

Micro and Nano Systems Letters

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]
MTC		-Free from contamination	-Magnetic bead size must be large enough as compared to the sample	[14]-[18]
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]
		-Cell aspiration can be done without cell bursting	-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	-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	-Inappropriate amount of force may cause cell bursting
		-Takes place in fluid environment	-Amount of force needed must be made prior known
		-Load cells fixed to the walls of flow chamber	-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
		-Low cost	-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]
		-Widely used to study cell deformation	-Inefficient trapping
		-Adjustable dimensions to suit different cell types	-Neglecting the effect of membrane rigidity and viscosity
		-Variety of geometry structure	-Neglecting the effect of membrane rigidity and viscosity
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
		-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
		-Enables pulse free pumping	-High energy consumption and high voltage

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