Table 5 Overview of the commonly employed methods used to qualitatively and quantitatively assess maternal-fetal particle transfer
Ref | Method | (Semi-) Quantitative and/or qualitative assessment | Strengths | Limitations | NPs studied |
|---|---|---|---|---|---|
Imaging techniques | |||||
NP visualization | Easy, rapid, low cost, non-destructive | Low contrast, staining artifact, no NP sizing | Ag, Au, Fe2O3, Fe3O4, SPIONs, and magnetic NPs | ||
NP visualization | High sensitivity, 3D reconstruction (optical sectioning), increased optical resolution (no out-of-focus signals), multiplexing capabilities, non-destructive | Photobleaching, uncoupling or leakage of fluorophores, no NP sizing | PS, PGMA, SPIONs, and SiO2 NPs | ||
Ex vivo/in vivo fluorescence imaging [101] | NP visualization | Easy, low cost, non-invasive, multiplexing capabilities, whole-body imaging possible, not sample destructive, real-time | Limited imaging depth (tissue penetration < 1 cm, autofluorescence), photobleaching, uncoupling or leakage of fluorophores, no NP sizing | QDs, Au, PS, SiO2, and TiO2 NPs | |
NP visualization | Easy, low cost, multiplexing capabilities, non-destructive | Limited (axial) resolution and imaging depth (autofluorescence), photobleaching, uncoupling or leakage of fluorophores, no NP sizing | Au, PGMA, PS, SiO2, and TiO2 NPs | ||
NP visualization | Easy, multiplexing capabilities, improved SNR (differentiation of NP signal from autofluorescence), high specificity, non-destructive | No NP sizing | Ag and Au NPs | ||
MRI [96] | NP visualization | High resolution, non-invasive, non-destructive, whole-body imaging, real-time, not limited by tissue depth | Restricted to magnetic NPs, slow image acquisition and long post-processing times, uncoupling of contrast agents, no NP sizing | SiO2 and PGMA NPs | |
NP-cell interaction and visualization | High resolution, combination with EDX for elemental analysis, no quenching/bleaching/uncoupling effects | Time-consuming, expensive, destructive, staining and shrinking artifacts, only applicable for electron-dense NPs, no NP sizing, not suitable for living material | TiO2 NPs | ||
[1, 23, 24, 27, 29,30,31,32, 41, 43, 45, 47, 49, 52, 54, 58, 60, 61, 73, 75, 91, 92] | Ultrastructural analysis and (subcellular) NP visualization | High resolution, combination with EDX for elemental analysis, no quenching/bleaching/uncoupling effects | Time-consuming, expensive, destructive, staining and shrinking artifacts, only applicable for electron-dense NPs, no NP sizing, not suitable for living material | Ag, Au, BC, DEP, Fe3O4, SiO2, TiO2, and PS NPs | |
[1] | Two-photon fs pulsed laser microscopy [105] | NP visualization | High sensitivity and specificity, label-free, non-destructive | No NP sizing | BC particles |
[71] | Ultrasound imaging [106] | NP visualization | Low cost, real-time, non-destructive | Sensitive to blood flow and tissue elasticity, uncoupling of contrast agents, no NP sizing | SiO2 NPs |
[61] | NP visualization | High resolution, high specificity and sensitivity, large penetration depth | Destructive, radiation damage, no NP sizing | Au NPs | |
Spectroscopic techniques | |||||
AAS [109] | Elemental composition, NP quantification (LoD: high ppb range) | Accurate, fast, easy, high sensitivity and specificity | Time-consuming, expensive, no information on cellular NP localization | SPIONs, Ag, Au, and CdO NPs | |
Gamma spectroscopy [96] | Identification and quantification of radioisotope-labeled NPs | High sensitivity and specificity, | Expensive, radioactive labeling, radiation safety requirements, limited spatiotemporal resolution | Fullerene, Ag, Au, and SiO2 NPs | |
[22, 23, 31, 32, 38, 45,46,47, 50,51,52, 55, 58, 60, 61, 64,65,66,67,68, 72, 76,77,78, 81, 83,84,85,86] | Elemental composition, NP quantification (LoD: ppt range) | Rapid, high sensitivity and specificity, little sample preparation (no labeling needed), high sample throughput (all elements 2–6 min) | Chemical interference (e.g., argon from plasma), dissolution of NP, quantification of non-metal-based NPs not possible, no information on cellular NP localization | QDs, Ag, Au, CdO, CeO2, Cu, ZnO, and TiO2 NPs | |
Elemental composition, NP (cellular internalization) quantification (LoD: low ppb range) | Reproducible, high sensitivity and specificity, no chemical interference, little sample preparation (no labeling needed), high sample throughput (5–30 elements/min) | Spectral interference, dissolution of NP, quantification of non-metal-based NPs not possible, no information on cellular NP localization | QDs, Ag, and SiO2 NPs | ||
[33] | MPS [114] | NP quantification | High sensitivity, little sample preparation (no labeling nor purification needed) | Time-consuming, expensive, quantification of non-magnetic NPs not possible | SPIONs |
[69] | NP quantification | Easy, fast | Low sensitivity, no information on cellular NP localization | Fe2O3 NPs | |
Other techniques | |||||
[36] | NP quantification | High resolution, highly reproducible, rapid, size separation possible | Low sensitivity, no information on cellular NP localization | PS NPs | |
[27] | Flow cytometry [97] | NP (cellular uptake) quantification | Easy, rapid, high sample throughput, multiplexing capabilities, not sample destructive | No information on cellular NP localization, uncoupling or leakage of fluorophores | PS NPs |
[27] | HPLC (fluorescence detection) [118] | NP quantification | Rapid, size separation possible | No information on cellular NP localization, uncoupling or leakage of fluorophores | PS NPs |