The recorded force-displacement curve for Samples 1-3 (Figure ) demonstrates that the whole compression process was kept in elastic region, assuring the HMNs did not fail during the compression experiments. The penetration performance and depth of HMNs were subsequently accessed on Samples 4-6 by parafilm penetration tests . A force load was applied at a speed of 1 mm/min and removed when the resistance reached 40 N and held for 30 seconds . The deformation resistance gradually decreased to approximately 25 N (Figure ). After the separation of HMNs, the SEM image (Figure ) of the HMNs and the optical images of parafilm layers (Figure , from the 1 st layer to the 6 th layer) were captured. The penetration efficiency was analyzed according to the holes created on each parafilm layer and the results were shown in Figure . It can be concluded that 82.67 ± 1.89 % of the fabricated HMNs were able to pierce about 3 layers of parafilm, affirming the successful penetration of HMNs to the dermis layer for ISF sampling . Thus, the 3D-printed biocompatible HMNs demonstrated excellent mechanical stability and penetration performance for ISF sampling.