Table 1.

OMI in systems biology

Techniques	Physical processes	Resolution	Sensitivity	Penetration	Observation methods	Probes	Indicator localization	References
WFM LSCM MPLSM	RNA transcription and expression	High	High	High	DFI, FRET	FPs	In vitro, cells, tissues, organism	[63, 64, 71–76]
	Protein localization and dynamics				DFI	FPs	In vitro, cells, tissues, organism	[51, 52, 65, 77–79]
	Subcellular organelle dynamics				DFI, FRAP	FPs	Cells	[80–82]
	Protein interaction				FRET, FLIM, FCS	FPs, cpFPs	Cells, mouse	[46, 47, 49, 57, 59, 60, 83–88, 140]
	Protease and kinase activity				FRET	FPs		[89–96]
	Calcium				DFI, FRET	FPs, cpFPs	Cells, C. elegans, fish, mouse, Drosophila	[14, 27, 28, 97–101, 130–138]
	cAMP, cGMP				FRET	FPs	Cells	[102–106]
	Electrical activity				DFI, FRET	FPs	Cells	[107–109]
	pH				DFI, FRET	FPs	Cells, mouse	[110–112, 139]
	Tumor				DFI	QDs	Mouse	[33, 141, 142]
SHIM	Biomacromolecules	Low	High	Low	NI	–	Mouse, C. elegans, brain tissue	[116–118]
	Membrane potential				NI	Dyes	Cells, brain tissue	[119, 120]
OCT	Morphology of tissue	High	Low	High	EI	–	Human	[122, 123]
	Activity and disease of organ				EI	–	Human	[124, 125]
RS	Composition of structure	Low	High	Low	NI	–	Brain tissues, bronchial tissue	[126, 127]
FT-IR	Kinetics of reaction intermediates	Low	High	Low	NI	–	Yeast extract, fish liver	[67, 68]

Abbreviations: DFI, Direct fluorescent imaging; NI, nonlinear imaging; EI, light-echo imaging