The release of cargo from soft vesicles is an essential step for chemical delivery related to various processes, including liposome drug delivery, exosome-mediated cell signaling, vesicular transport, intracellular vesicular trafficking, exocytosis, etc. Among these, exocytosis, with a key role in cell communication and possibly a therapeutic target for disease of the nervous or endocrine system, has attracted increasing attention even though its mechanism and dynamics has been investigated for decades. Electrochemical techniques, especially amperometry in combination with ultramicroelectrodes, have been developed as an approach to monitor the release of chemical cargo during the exocytotic event with high sensitivity and spatial-temporal resolution. The experimental signals of monitoring exocytosis, in the form of amperometric "spikes," usually contain complex information about vesicle geometry, cargo quantity, and release dynamics through the exocytotic pore driven and controlled by the SNARE protein complex, actin, and dynamin. For those vesicles isolated from cells, we can also trigger their cargo release (simulate exocytosis) and record the release signal again as "spikes" with our previously reported approach, called vesicle impact electrochemical cytometry (VIEC). However, some difficulties still exist in the dynamic analysis of these spike signals, especially for those involving complex release processes which are difficult to quantitatively describe. Usually, the exocytotic spike is observed as an asymmetrical peak, different in the rising and falling time. The spike decay lasts a longer time and for some spikes this current decay can be fit to a single exponential (I=Ae -αt ), whereas for other spikes to a double exponential (I=A 1 e -αt +A 2 e -βt ) function. The single exponential (SigExp) decay can be easily explained with a diffusion model where the release pore is static. In contrast, the widely observed double exponential (DblExp) decay events during exocytotic release appear to indicate that additional processes besides simple diffusion are involved. and Yue et al. suggested that the DblExp mode of vesicular release might result from the exocytotic pore closing mediated by membrane proteins. Oleinick et al. showed that the interaction of catecholamines with the protein dense core matrix in vesicles can lead to spikes with DblExp in the latter part of the spike. Interaction between chemical cargo and vesicle dense core is certainly important, however, interactions have been shown between the chemical cargo and membranes and these might play a broader role in vesicle release dynamics. These interactions could be broadly applicable as they will be observed in all vesicles, not only in the vesicles with a dense core. To the best of our knowledge this has not been investigated to date. Interaction between the chemical cargo and the membrane, i.e. an adsorption-desorption process, adds an element of complication to the release process model and provide a mechanism of biological regulation. Numerical approaches, represented by the finite element simulation, provide a powerful tool for solving the problems related to complex processes which are difficult with direct analytical approaches. Based on the numerical analysis of the spike signals recorded through the VIEC technique, we can reconstruct the physical model of the entire vesicle release process 28 and include an inverse estimation of the relative specific physical parameters, such as the vesicular pore size, diffusion coefficient of cargo chemicals, desorption rate constant, etc. These parameters can clearly describe the dissociation of cargo from the membrane and how it alters general vesicle release dynamics.