## Materials and Methods
### Microcantilever Experiments  
The interaction of EVs and MCs was probed by the Cantisens Research platform (Concentris GmbH, Basel, Switzerland), that allows simultaneous experiments in both static and dynamic mode. The instrument is equipped with a microfluidic system to deliver the liquid and for all the experiments the flux rate was set to 0.42 \(\upmu\)L/s. The readout of the deflection of each individual MC is performed simultaneously by multiple lasers focused to the end of the MC and the temperature of the measurement chamber was set at 25 \({}^{\circ}\)C. MC arrays architecture consists of eight Si MCs with the top faces coated by a 20 nm Au thin film.  
For experiments in static mode, arrays of eight rectangular MCs of the same size were employed, namely 500 \(\upmu\)m long, 100 \(\upmu\)m wide, and 1 \(\upmu\)m thick (Concentris GmbH, Basel, Switzerland). Four of them used as internal reference were passivated with polyethylene glycol, 3400 Da (PEG 3k) in a capillary system for 3 h. The other four MCs were passivated with 6-mercapto1-hexanol in capillary system for 3 h. MC deflection can be related to the change in surface stress by [PERSON]'s equation [27]  
\[\Delta\sigma=\frac{\text{E}\,\text{t}^{2}\,\Delta\text{z}}{4\,\text{l}^{2}(1- \text{v})} \tag{1}\]  
where t is the thickness of the cantilever, l is the length, E is [PERSON]'s modulus (E = 169 GPa), and v the [PERSON]'s ratio (0.25 for rectangular MC).  
For experiments in dynamic mode, MCs were chosen with different lengths, and thus resonance frequencies (Concentris GmbH), in order to minimize mechanical crosstalk. The resonance frequency steps between MCs are 26 kHz on the first mode (according to Sader Inviscid Model [28]). MCs are 100 \(\upmu\)m in width and 7 \(\upmu\)m thick, the lengths are 212, 315, 249, and 500 nm repeated twice, and density of 2330 kg/m\({}^{3}\). The determination of the added mass is calculated according to [28]. The assumptions consider the effect of the EV deposition purely mass-related and negligible the contribution in the change of spring constant. This is a good approximation for the adsorption of a soft layer of biomolecules onto the MC surface, as reported in [29; 30]. Density and volume are considered constant over the whole experiment and for all samples. For further details, please refer to [28; 29]. Knowing the resonance frequency before (f\({}_{\text{a}}\)) and after (f\({}_{\text{b}}\)) the adsorption of EVs, the adsorbed mass is calculated as  
\[\Delta\text{m}=G_{\text{P}}^{2}C_{\text{n}}^{2}\text{E}\left(\frac{1}{\text{f }_{\text{b}}^{2}}-\frac{1}{\text{f}_{\text{a}}^{2}}\right) \tag{2}\]  
Figure 1: Protocol of the experimental steps. Scheme of the experimental process.  
where \(\rm G_{p}\) is an empirical coefficient that takes into account the differences between the experimental and ideal mechanical behavior of a microcantilever (internal defects and geometrical differences from the nominal values), \(\rm C_{n}\) is equal to \(\rm\beta_{n}^{2}/2\pi\sqrt{3}\), where \(\rm\beta_{n}\) are the solutions of the equation \(\rm cos\ \beta_{n}\rm I\cosh\beta_{n}\rm I+1=0\), and \(\rm E\) is the young modulus of the microcantilever [31].  
Before each experiment, MCs were immersed in acetone for 30 min and cleaned by UV/ozone plasma (PSD-UVT, Novascan Technologies, Boone, IA, USA) for 30 min. In all the experiments, the MCs were stabilized in PBS 10 mM for about 3 h before the injection of EV solution in PBS 10 mM. After injection, the EV solution was allowed to flow in the measurement chamber for about 2 min and then the flow stopped for about 30 min, in order to allow interaction equilibrium to be attained.