Table 1 Micro/nano devices for intracellular measurements

From: Voyage inside the cell: Microsystems and nanoengineering for intracellular measurement and manipulation

Measurement

Technique

Description

References

Electrical properties

3D kinked silicon nanowire

NanoFET built on kinked nanowire; phospholipid bilayer coated; sensitivity: 4∼8 μS/V for conductance measurement; capable of pH measurement with a 58 mV/pH sensitivity

20,28,29

 

Branched nanoFET

Hollow SiO2 structure; 5 nm probe size with controlled taper tip

31,32

 

Multielectrode arrays

Parallel sensing; higher throughput; unknown disturbance to cell activities; unable to control individual insertion depth

33,36,37,38

 

Carbon nanotube

High tensile strength and elastic modulus; high electric current density; 100∼200 nm tip size

34,44,45,46,51

Mechanical properties

Modified AFM tip

Fabricated via FIB or direct growth/assembly of nanowires on AFM tips; capable of measuring nuclear mechanics and mapping intracellular stiffness; 30∼180 nm tip diameter; 0.5∼6 μm tip height

19,34,48,60,61,62

 

Vinculin-fused fluorescent protein (FP)

Force sensitive focal adhesion proteins tagged with GFP used to visualize the formation of local complex in response to local forces

96

 

Cdc42/Src-specific FP

Local mechanical stimulation induces changes in the FRET level of Cdc42/Src-specific fluorescent signal

97,104

 

Lamin-A/Fib GFP

GFPs conjugated to nuclear Lamin-A or Fib reveal the shape and motion changes of nucleus in response to mechanical stimulation

107

Temperature

CdSe quantum dots

Temperature changes convert to spectrum shift; first experimental demonstration of heterogeneous intracellular temperature

76,77

 

Polymetric nanoparticles

Consist of a thermosensitive unit, a hydrophilic unit, and a fluorescent unit; 0.18∼0.58 °C resolution; 0.96 °C average temperature variance in COS7 cells

18

 

Nanodiamond

Ultrahigh 1.8 mK resolution; thermally induced lattice strains cause the changes in transition frequency

46,71

 

GFP

Intracellular temperature variations cause GFP characteristic changes in blinking relaxation time or polarization anisotropy

113,114,115

Chemical sensing (e.g., pH, Ca2+, Cu2+, Cl−)

Dual-emission nanoparticle

Incorporation of a sensing dye and analyte insensitive reference dye enables ratio metric measurement

84,85

 

Core-shell nanoparticle

A reference-dye-rich core coated with a thin layer of sensing-dye-rich silica shell; measured endosome pH varying from 5.0 to 6.5

88,89

 

GFP

Fluorescence and absorbance properties of mutant GFP reflect intracellular pH level

99,111,112

Pressure

MEMS sensor

Intracellular pressure deflects device membrane and alters the intensity of reflected light; introduced into cell via lipofection; device size: 4 × 6 × 0.4 μm

116

Optical measurement

SiO2 nanowire

Works as either a light source for imaging or a spectrometer to collect optical signal; can be coupled with untethered nanoparticles to measure intracellular pH or temperature; 100∼250 nm tip size

35