Extended Data Fig. 8: Fabrication of MNPs with OPMR and mRNA-LNPs.
From: On-patient medical record and mRNA therapeutics using intradermal microneedles

Vacuum through devices were custom designed and fabricated; (a) Top, (b) middle and (c) bottom layers of the device were designed using 2D CAD modeling. The top and bottom pieces were made by laser cutting 1/8’-thick Acrylic sheets (McMaster-Carr 8589K41), and the middle piece was made by laser cutting 0.045’-thick Acrylic foam adhesive sheet (McMaster-Carr 1630N24). The middle layer was adhered to the top layer first (d), and then the bottom layer was adhered to complete the assembly (e). Patterned MNPs were fabricated either by manually knocking out QD-loaded needles (f) or by selectively loading QDs using a mask (g). These two methods did not make a difference in signal transfer or signal longevity results. Patterned masks can be created by hole-punching or laser-burning during MNP fabrications. Other viable approaches to fabricate patterned MNPs could involve molds that consist of adjustable pins. Once a pattern is generated, a robot could push selected pins to create a positive mold representing the desired pattern in real time. The adjustable pin arrays could also directly press against pre-made full array MNPs to punch out specific needles. (h) Master molds of 20x20 needle arrays are 3D printed for negative PDMS mold fabrication. (i) A patterned mask is placed on top of the PDMS mold. (j) QD-PMMA solution is dispensed on the masked PDMS under vacuum to selectively load the dye into the needle tips in a pattern. (k) The mRNA-LNP-polymer solution is then added to the mold for the mRNA-OPMR MNP fabrication. (l) The footprint of dispensed mRNA-LNP-polymer solution while drying. (m) Once the polymer dries, a Delrin backing is attached to the back of the MNP, and the patch is removed from the PDMS mold to be further dried in a desiccator under vacuum for 48 hours. Once an MNP is applied to the skin, the microneedles are designed to readily dissolve within minutes, simultaneously delivering a clinically relevant dose of mRNA vaccine and an NIR pattern that represents corresponding medical information (e.g., vaccine type, manufacturer, vaccination date) to the dermis layer, producing effective immunogenicity and long-term information recording on patients. (n) Cross-sectional scanning electron microscopy (SEM) images of an OPMR-mRNA-MNP needle near the tip showing the OPMR dye (QD-PMMA microparticles; 10 µm), near the mid-body region where mRNA vaccine solution is loaded and at the backing of the needle where the PVA-PVP material is showing a smooth surface. Imaging was performed once. (o) Co-loaded OPMR-mRNA MNP needles will have OPMR dye concentrated at the needle tips and vaccine loaded in the needle bodies as depicted with pink color dye.