This methodology was taken from our previous study (46). MNs were fabricated using five uniform silicone molds from Blueacre Technology Ltd. The MNs have a 300-μm-diameter round base, which tapers for a height of 600 μm before ending in a tip that is roughly 5 μm in radius. The MNs were arranged 600 μm apart, tip to tip, in a 20 by 20 array. First, aqueous PVA solution (10 weight %, 100 μl) was prepared and deposited in a silicone mold, which was kept under vacuum for 20 min. The mold was then centrifuged at 500 rpm for 20 min in a Hettich Universal 32R centrifuge to compact the gel solution into MN cavities. Then, additional aqueous solutions of PVA (100 μl) were loaded into the mold, and the above procedure was repeated several times, until a total volume of 500 μl of PVA solution was added to the mold. Last, each micromold was dried under vacuum for another 24 hours. Once dried, the MN array patch was carefully separated from the silicone mold for further application. An FEI Verios 460L field-emission scanning electron microscope was used to assess the morphology of the MNs. Cy5.5-labeled PVA MN was prepared similarly. In short, Cy5.5 was first used to modify PEG5K-NH2, which was subsequently dissolved in PVA aqueous solution to label the MN. The modification of Cy5.5 with PEG5K could increase its water solubility and retention in MN. A stress-strain gauge was used to determine the mechanical strength of the MNs by pressing a stainless steel plate toward the MNs on a DTS delaminator. The initial gauge between the tips of MN and the plate was 2.00 mm, with the load cell capacity of 10.00 N. The plate approached MNs at a speed of 0.1 mm/s. The force that led to the failure of MNs was defined as the force at which the needle began to buckle.

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