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. 2022 May 16;14:854957. doi: 10.3389/fnsyn.2022.854957

TABLE 1.

Common secondary ion mass spectrometry (SIMS) and electrochemical methods for neuronal and synaptic measurements.

Methods Applications Advantages/disadvantages
Time of flight secondary ion mass spectrometry (ToF-SIMS) Imaging spatial distribution of ions up to ∼ 2,000 Da (metabolites, molecular lipids, small peptides)
2D and 3D imaging possible
+ Parallel detection within a large mass range (0-2,000 Da)
+Suitable for non-targeted imaging (non-labeling)
+ Many primary ion sources available
- Topographical sample effect
- Spatial resolution possibly ∼ 250 nm
Nanoscale secondary ion mass spectrometry (NanoSIMS) Imaging spatial distribution of monoatomic or diatomic ions at subcellular resolution
2D and 3D imaging possible
+ Spatial resolution ∼ 50 nm
- Molecular information lost
- Parallel detection up to 7 ions
- Isotopic labeling often employed
Single cell amperometry (SCA) Quantification of the number of neurotransmitters released from individual vesicles + High temporal resolution (sub-milliseconds to a few millisecond)
- Cannot distinguish between catecholamine and other electroactive molecules at the same time
Vesicle impact electrochemical cytometry (VIEC) Quantification of the total number of neurotransmitters stored inside individual vesicles
Investigation of the effects of drug treatments on vesicle properties
+ easily manipulate the surrounding environment of vesicles
- Risk of leakage of vesicular transmitters and changes of vesicle properties during the vesicle isolation process
- Cannot distinguish between catecholamine and other electroactive molecules at the same time
Intracellular vesicle impact electrochemical cytometry (IVIEC) In situ approach quantifying total vesicle content within their cellular environment (in the cytoplasm) + Possible to change external factors such as osmolarity, pH and pharmaceutical treatments with minimal impact on the cells
- Cannot distinguish between catecholamine and other electroactive molecules at the same time
Fast scan cyclic voltammetry (FSCV) Study of the behavior, addiction, and disease of live animals by measuring in vivo the rapid changes of neurotransmitters + Possible to simultaneously quantify and identify various analytes by selecting voltage limits of the interested analyte
- Cannot measure basal levels of neurotransmitters, governed by phasic and tonic neuronal activity, only fast change of electroactive species because the background current can be only stable for a brief time