We constructed a finite element model to simulate this desorption-release process. The finite element model depicts a spherical liposome (radius 188 nm, experimental average) with a round pore in its membrane. On the other side, the total quantity of chemical cargo was set as 151000 molecules (according to the average experimental current spikes of charge Q=48 fC), but divided into absorbed species (Q s , where s indicates the membrane inner surface) and freely diffusing species (Q f , f indicates the freely moving species). Species need to reach an adsorption-desorption equilibrium before release. If we pre-set parameters describing the adsorption-desorption process, such as the adsorption rate constant (k ads ), of adsorbed molecules in the saturated state (Γ s ), then the Q s and Q f can be calculated by use of Langmuir's adsorption equation and converted into an initial concentration on the membrane (C s,0 ) and in the liposome cavity (C f,0 ). After pore generation, the freely diffusing species exit the pore, while the absorbed species require time to dissociate from the membrane and transfer into the solution phase. The flux of molecules flowing out the pore is converted into current that is then used to fit to the experimental spike and estimate the key parameters in the desorption-release process, including the desorption rate constant (k des ) and radius of the pore (R p ). The Monte Carlo optimization method was used to facilitate these estimates owing to its advantages such as high efficiency to solve complex problems and exemption of any a priori hypothetical relationship between current spikes and initial parameters (see calculation protocol and details in Supporting Information). Four groups of typical DA and 5-HT spikes were analyzed by the finite element simulation. A pair of the experimental spikes and their best fit results are shown in Figure . The DLL spikes show a better fit with a DblExp decay, whereas the SLL spikes fit better to a SigExp decay. By comparing the estimated desorption rate constant (k des ) and pore radius (R p ) corresponding to DA or 5-HT spikes, the pore sizes of both groups (see Table ) cover a similar range (40~90 nm for DLL vs. 40~80 nm for SLL), while the k des of DA is obviously smaller than 5-HT (10 2.3~3.0 s -1 for DA vs. 10 3.5~5.1 s -1 for 5-HT). This smaller k des leads to the slower desorption rate (r des ) and longer time to end of the release, which is consistent with a longer decay for DLL spikes. The smaller k des of DA may result from the greater number of H-bonds (~3 bonds) formed between dopamine and the polar neutral lipid compared to serotonin which can form only 2. The higher free energy of DA to lipid binding (~21 kJ/mol) compared to 5-HT (~14 kJ/mol) 27 make it harder for DA to dissociate. These results support our assumption that different desorption rates alter the release dynamics between these two monoamines (Figure ). It also provides a new perspective for the DblExp decay in the study of bio-vesicular release by the VIEC experiment or exocytosis measured by single cell amperometry. However, it is worth noting that, in the VIEC analysis of native biological vesicles, the proportion of DblExp fitting (empirically 40%~60%) is much higher than that of liposomes (empirically <10%, when the ratio of χ 2 (single)/χ 2 (double)>2 set as the cutoff). This phenomenon likely indicates that the dense core in the bio-vesicles still also plays an important role in regulating release from the vesicle.