Porous Polymer Microneedles with Interconnecting Microchannels Toward Efficient Sensing of Interstitial Fluid

The microneedle array, the two-dimensional array of small needles of submillimeter length, is a minimally invasive alternative to conventional hypodermic needles. It penetrates skin and bypasses the diffusion barrier of stratum corneum and facilitates drug delivery as well as sampling and electrochemical sensing of biologically relevant molecules in interstitial fluid.1,2 Microneedles for sampling interstitial fluid fall into three types: hollow microneedles, hydrogel microneedles, and porous microneedles. Hollow microneedles have a bore inside the microneedle made by a photolithographic process. Hydrogel microneedles swell by absorption of interstitial fluid, and ex vivo analysis has been achieved. Porous microneedles have random pores in the body of the microneedle, and they have advantages such as a large pore volume ratio, efficient capillary action by many microchannels, large surface area for immobilization of sensor molecules, etc. Making porous microneedles with a polymer material has the advantages such as biocompatibility, easy fabrication by molding, a variety of molecular structures for tuning properties, etc. Despite their apparent advantages, the fabrication of porous polymer microneedles has been a challenge. In this study, we have fabricated microneedle arrays made of a porous polymer with interconnecting micropores.3 A porous polymer monolith is synthesized by polymerizing glycidyl methacrylate (GMA) with bi- and trifunctional crosslinkers by the irradiation of 365 nm UV in the presence of poly(ethylene glycol) in 2-methoxyethanol as a porogen, followed by washing with methanol/water.4 We fabricated a porous polymer monolith of this poly(glycidyl methacrylate) (PGMA) in a soft polydimethylsiloxane mold. The resulting microneedle array was a hard, opaque solid (Figure (a)), whereas a control with no porogen was transparent. Scanning electron microscopy (SEM) observation revealed that microneedles made with a porogen have interconnecting pores with ~1 µm in diameter on the surface and interior (Figure (b)). The porous microneedles with varied porogen ratios were fabricated to investigate its effects on porosity, water absorption speed, and skin penetration efficiency. Porosity was measured by weight increase of the porous microneedles after immersion into water. As an porogen ratio was increased, the porosity increased as well. The pore connectivity parameter, defined as (porosity)/(porogen ratio), versus a porogen ratio showed a sigmoidal profile that converges to unity, which indicated all the pores are interconnecting and accessible from the surface above a certain threshold of the porogen ratio. Water absorption speed of the porous microneedles was evaluated by a piece of water sensor paper that turns blue upon water absorption. The water sensor was attached on the top surface of the microneedle array, and the response time of the water sensor was measured. The response time decreased sharply to less than 20 minutes at the 36% porogen ratio, and this was consistent with the threshold of the porogen ratio for pore connectivity. The microneedle arrays were applied to a pig skin with the force of 1 N/needle, and punctured spots of the pig skin were stained with trypan blue. The microneedle arrays with lower porogen ratios had higher penetration efficiencies, and the porous microneedles with >80% penetration efficiency was achieved for the porogen ratio no more than 49%. With the lower porogen ratios, the porous microneedles become mechanically more robust, and the tips of the microneedles become sharper. In summary, by optimizing the porogen ratio (Figure (c)), we successfully developed porous polymer microneedles that combine fast water absorption speed and high skin penetration efficiency. The fabricated porous microneedles are a potentially versatile tool for sampling and sensing of interstitial fluid. References [1] M. R. Prausnitz, Adv. Drug Deliv. Rev., 56,581 (2004). [2] L. Ventrelli et al, Adv. Healthc. Mater., 4,2606 (2015). [3] L. Liu et al, submitted. [4] J. Courtois, E. Byström and K. Irgum, Polymer, 47, 2603–2611 (2006). Figure 1