Abstract: In surgery of epilepsy, a patient's cranium is opened for intracranial electroencephalogram (iEEG) measurement or electrical stimulation to treat a part of a brain causing seizures [1]. Conventionally, intracranial metal electrodes with a silicone rubber substrate have been widely used in iEEG measurements during surgery. However, the substrate of the electrode is stiff and needs to be pressed down to fit on the surface of the brain, which increases the tissue damage during the insertion into in a deep sulcus called a longitudinal cerebral fissure or a Silvian fissure. Besides, the low transparency of the electrode substrate decreases the immediate recognition of the diseased area, and the lack of permeability of that also cause damage to the brain in long term treatment including an implantation of the electrode. Herein, a flexible intracranial electrode using a hydrogel as a substrate was developed [2] . A soft carbon fabric electrode was embedded in a hydrogel composed of poly (vinyl alcohol) (PVA). The PVA hydrogel has excellent flexibility, biocompatibility, water content, and hydrophilicity, which leads to well adhesion and conformability to the brain. Moreover, the transparency of PVA hydrogel is expected to improve the visibility of the brain under the substrate and its permeability ensure adequate fluid delivery. Carbon fabric electrodes were fabricated by cutting the electrodes and lead wires out of the fabric and applying an insulation coating. The non-insulated electrode surface was coated with conductive particle polymer poly (3,4-ethylenedioxythiophene) (PEDOT) to increase the surface area and increase the electrical capacity. This process is to prevent electrolysis from occurring during electrical stimulation[3]. A gel precursor solution was prepared by dissolving PVA in distilled water and adding dimethyl sulfoxide (DMSO). The electrodes were embedded in the precursor solution and gelated by repeated freezing and thawing cycles. DMSO provided an uniform and clear gel, and to avoid its irritation, the obtained gel was soaked and washed well in saline. Figures 1 shows the electrodes placed on the brain model. While the conventional electrodes with silicone substrate hardly followed the shape of the object (Figure 1a), the electrodes with hydrogel substrate followed the object well (Figure 1b). The object was not clear to observe through the conventional silicone substrate, and that substrate did not swell the water droplet placed on the surface (Figure 1c). In contrast, the hydrogel-based substrate was clear after the adhesion onto the brain model, and the water droplets placed on the surface were spread over the entire surface and adsorbed to the hydrogel-based substrate. These results indicated that electrodes with a hydrogel substrate could adhere well to the brain surface while minimizing damage to the tissue, and allowing observation of the affected area during surgery. Our developed electrode with soft, hydrophilic, and soft hydrogel substrate were promising device for the treatment of epilepsy, overcoming the conventional problems and leading to new medical approach. References [1] S. Noachtar, I. Borggraefe, “Epilepsy surgery: A critical review”, Epilepsy Behav. , 15, 66-72, (2009) [2] S. Oribe, S. Yoshida, S. Kusama, S. Osawa, A. Nakagawa, M. Iwasaki, T. Tominaga, and M. Nishizawa, “Hydrogel-Based Organic Subdural Electrode with High Conformability to Brain Surface”, Sci. Rep. , 9, 13379, (2019). [3] S. Yoshida, K. Sumomozawa, K. Nagamine, and M. Nishizawa, “Hydrogel Microchambers Integrated with Organic Electrode for Efficient Electrical Stimulation of Human iPSC-Derived Cardiomyocytes”, Macromol. Biosci. , 19, e1900060, (2019) Figure 1

Abstract: A smart contact lens (CL) is an attractive wearable device that could enable noninvasive monitoring of physiological information and augmented reality display in addition to vision correction. Whereas, the CL is one of the causes of dry eye syndrome due to more rapid moisture evaporation through the CLs than that from the normal tear film covered by a lipid layer. Conventional rehydration by regular eye drops takes time and efforts. The only example so far of a smart CL for maintaining the moisture is that of Lee et al., who developed a CL coated with single layer of graphene which decreases the evaporation. Hence, there is still a high demand to develop a CL equipped with an anti-dehydration function. We here designed a charge-fixed soft CL generating electroosmotic flow (EOF) under an electric field for maintaining the moisture of the lens (Figure 1a) [1]. The CL supplies tears via EOF from the tear meniscus (temporary tear reservoir) behind the lower eyelid. EOF is the motion of water induced by an applied electric field across a fluid conduit like a capillary tube or a porous material such as hydrogels. When the fluid conduit contains fixed electrical charges, the dominant electromigration of the mobile counter ions produces net water flow. The soft CL made of negatively charged hydrogel were fabricated by copolymerizing methacrylic acid (MA, 0 – 15 wt%), 2-hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA). At First, we evaluated the efficiency of EOF generation for each of the 0.2 mm thick hydrogel films. DC currents of 1.0, 2.0, and 3.0 mA were applied to the films sandwiched by the side-by-side Franz cell with a horizontal capillary, and the flow velocity of EOF was calculated from the movement of the water surface in the horizontal capillary. These results indicate that a hydrogel with a high MA content is suitable for effective EOF generation in hydrogels. Secondly, compression tests were performed to the films to evaluate the indentation fracture toughness. The larger MA content tends to make the hydrogel become brittle and the hydrogel with 15 wt% MA was easily broken by folding. By considering both the results of the EOF strength and the fracture toughness, we mainly used the 10 wt% MA hydrogel in subsequent experiments. The water content and the conductance of the films were separately monitored at 100 kHz during the slow drying under 75% humidity. This result supports that the change in water content in the hydrogel film can be traced by the conductance measurement (Figure 1b). Finally, the EOF-based moisturization for the battery-mounted CL was demonstrated using an enzymatic fructose–oxygen fuel cell [2], in which the CL was put on a hemispherical jig (ocular model) equipped with printed Ag/AgCl electrodes for conductance measurements (Figure 1c). The lower end (≈3 mm) of the CL was dipped in a buffer solution containing D-fructose to imitate a tear meniscus. Figure 1d shows the observed changes in conductance (moisture) of CLs without EOF (gray, natural drying) and with upward EOF generated by an enzymatic fuel cell (red). The results demonstrated that applying an upward EOF through the CL reduced the moisture loss of the lens compared to natural drying. Since the demonstration was conducted at a relatively dry condition (40% humidity) for the hanging CLs, it can be expected that the moisturization would be more effective in situations where CLs are put onto eye. From these results, we believe that the proposed hydrogel will promise development of a contact lens devices with an anti-drying function. Reference [1] S. Kusama, K. Sato, S. Yoshida, and M. Nishizawa, “Self-Moisturizing Smart Contact Lens Employing Electroosmosis”, Adv. Mater. Technol. 5, 1, 1–9 (2020) [2] Y. Ogawa, K. Kato, T. Miyake, K. Nagamine, T. Ofuji, S. Yoshino, and M. Nishizawa, “Organic Transdermal Iontophoresis Patch with Built-in Biofuel Cell,” Adv. Healthc. Mater. 4 , 506–510 (2015). Figure 1

Abstract: Iontophoresis has been widely studied to improve transdermal drug administration and transdermal extraction of interstitial fluids without patient’ stress. The stratum corneum (SC), outermost layer of skin, has the barrier functions preventing contamination of harmful molecules into a body, and also hinders the iontophoresis due to its high electrical resistance. Previously, we have reported the porous microneedle (PMN) prepared by a molding process and porogen method, which has a potential to lower the total resistance of the skin and improves the effect on iontophoresis [1]. However, the reproducibility of PMN’s porosity had room for further improvement since the solution of porogen used in the previous method could evaporate and change its volume. Here, we studied a few kinds of porogen solution with different boiling point to create the PMN with higher reproducibility. Furthermore, the ionic resistance of the electrolyte-containing PMN and that of the skin with the PMN were evaluated in order to design an efficient iontophoretic PMN patch. The PMN was fabricated by the combination of a molding process and the porogen method [1]. Briefly, a female mold for the PMN was made with PDMS by duplicating an acrylic plate drilled with an end mill and drill. The PMNs were made by using two stock solutions. A monomer stock solution was prepared by mixing the monomer glycidyl methacrylate, crosslinker trimethylolpropane trimethacrylate, and crosslinker triethylene glycol dimethacrylate. A porogen stock solution was prepared by dissolving 4.0 g polyethylene glycol (10 kDa) in 20 g diethylene glycol monomethyl ether (DEG) at 50 °C. The mixed solution composed of monomer, porogen and photoinitiator, was filled to the mold by removing the air between the mold and the solution in a vacuum desiccator. After that, UV irradiation was performed in a nitrogen environment to polymerize the solution, and finally the obtained needle was immersed in a mixed solution of water and ethanol to elute the porogen. The 2-methoxyethanol (2ME) was also employed to compare with DEG. The porosity of PMN using each solvent was calculated from the difference of weight of PMN in dry and wet conditions (pure water). The experimental porosity of the PMN using DEG was closer to the theoretical value and the shape of that was closer to the mold, indicating that DEG can contribute the reproducibility of the PMN fabrication owing to its higher boiling point than that of 2ME. In order to determine the mechanical strength of the PMN, the load test was performed by the force gauge. The load value at which the PMN broke was recorded. In addition, to verify the load when inserted to a pig skin, the PMN was placed on a pig skin and the load test was performed. We found that the PMN could withstand 11 N (0.297 N/needle), indicating it is possible to insert human skin without break because the necessary load for insertion is known to be 0.098 N/needle [2]. The PMN was inserted to the pig skin at ca. 6.5 N and no broken structure was observed after the insertion. The ionic resistance of the PMN soaked in Ringer’s solution was measured by using the AC impedance at high frequency (10-100 kHz), where 100-µm tip of the PMN was stuck to a 3 wt% agarose gel and a couple of electrodes made of carbon fabric was placed on the PMN and agarose gel. The PMN was inserted into human skin, and the resistance value of the skin before and after insertion were compared. The resistance value was calculated from the voltage value when a constant current of 1 µA was applied for 10 seconds. The resistance value of PMN was found to be about 250 Ω. By comparing the resistance values of the skin before and after PMN insertion, it was found that the resistance of intact skin was 1-6 MΩ, but decreased to several hundred kΩ. It was also found that the dispersion of the resistance value by individuals is smaller when PMN was used. In conclusion, we successfully fabricated PMN that is useful for effective iontophoresis with highly reproducibility. References [1]Liming Liu, Hiroyuki Kai, Kuniaki Nagamine, Yudai Ogawa and Matsuhiko Mishizawa, RSC Adv. 6 , 48630-48645 (2016) [2] Weijiang Yu, Guohua Jiang, Yang Zhang, Depeng Liu, Bin Xu and Junyi Zhou, Materi. Sci. and Eng. C 80 , 187–196, (2017) Figure 1

Abstract: An electrical skin patch that can be flexibly attached to the skin and activated in 30 s by adding water was developed by integrating a built-in flexible glucose/O 2 biobattery. The latter consisted of a glucose dehydrogenase (GDH)-modified anode and an iron(II) phthalocyanine (FePc)-modified cathode. The quick activation of the patch components by water addition deep inside the patch was achieved by using a flexible water-absorbing sponge containing glucose and buffer electrolyte. A patch current of about 10 μ A was maintained for more than 12 h by optimizing the amount of glucose and electrolyte contained in the sponge tank. The entire patch was soft and highly flexible to conform to curved skin surfaces, owing to its thinness ( 〈 2 mm) and the flexibility of all the patch components, including the enzyme electrodes based on the carbon fabric.

Abstract: Intraoperative biomedical devices are used in many medical fields such as monitoring, diagnosis and treatment of diseases. Subdural electrodes used in monitoring cortical activity contribute to an identification of pathological lesions in an epilepsy surgery and also the advance of elucidation of brain function. These electrodes as an interface with living systems should be flexible, biocompatible, and conformable to the curved brain surface. However, conventional electrodes consisting of metals such as Pt electrodes and a silicone-based substrate have not fully resolved mismatches between electronics circuit of a machine and biological wet systems, which causes a decrease of measurement accuracy and damage to bio-tissue[1]. In a previous study, we have developed a totally organic hydrogel-based subdural electrode by embedding a carbon fabric (CF) modified with poly(3,4-ethylenedioxythiophene) (PEDOT) into a poly(vinyl alcohol) (PVA) hydrogel substrate[2] . This wet electrode showed a good softness similar to the living tissue, a high conformability to a curved surface such as brains, and easy handling. Moreover, the totally organic nature would contribute to obtain clear MRI images without image artifacts. In this study, we have developed a new type of the hydrogel-based transparent subdural electrode in which the salt bridge acts as interface to bio-tissue (Fig. 1A). The present electrode consisted of three different parts, a salt bridge made of PVA hydrogel insulated by the microchannel made of Poly(dimethylpolysiloxane) (PDMS) membrane embedded into the PVA hydrogel substrate. The unique feature of the hydrogel-based electrode with the salt bridge system was aqueous-based interface to bio-tissue on which can be decreased an effect of the electrochemical reaction. The aqueous-based electrode similar to bio-tissue enable to be flexible, biocompatible, and conformable due to the use of highly soft and wet biomaterial. In addition, the device has an optical transparency which can contribute to obtaining detailed visual information under the electrode during surgical operations and would be valuable to the neuroscience in optogenetics. The PDMS membrane-based channel (thickness: 600 µm, width: 500 µm, height 100 µm) was fabricated by spin-coating at 700 rpm for 15 seconds on the SU-8 mold and bonding with an oxygen plasma treatment. PVA (Mw~145000) hydrogels for both a salt bridge (10 wt%) and substrate (15 wt%) were dissolved in a mixture of dimethyl sulfoxide (DMSO) and saturated KCl solution (mass ratio = 4:1). The PDMS membrane-based channel connected to the silicone tube for extension was filled with PVA hydrogel as a salt bridge, sandwiched by glass slides with 1.5 mm-thickness spacer which was filled with the PVA hydrogel, and crosslinked by freeze-thaw cycles (as -30 °C for 10 min and 4 °C for 10 min, each repeated three times). The fabricated electrode was rinsed twice in Ringer’s solution for one hour and overnight. The conformability was evaluated by the rate of contact area between electrodes and the surface of the curved sheet with various curvatures. In vivo recording was conducted on a porcine which was anaesthetized with the head fixed in a stereotaxic apparatus, and the dura mater was partially removed by a neurosurgeon to expose the surface of the cerebral cortex. Then, electrodes were placed on the exposed cortex on each hemisphere for simultaneous electrocorticography (ECoG) recording (2019MdA-324). Figure 1B shows the conformability of the developed and conventional electrode to the curved surface. The contact area of the hydrogel electrode showed more than 80 %, which was higher conformable than that of the silicone-based conventional electrode (~ 50 %). Figure 1C shows that the hydrogel electrode consisting of PVA hydrogels and PDMS as a highly transparent and biocompatible material, showed a sufficiently transparent to recognize the condition under the device. In contrast, the commercially available electrode was opaque due to thick silicone-based substrate and metal. As shown in Figure 1D, we successfully measured brain waves by the hydrogel electrode with the salt bridge system in vivo measurements on porcine. From this result, the salt bridge acted as the resistance for ionical connection and ionically connected from bio-tissue to electronic measurement machine. We successfully developed a new hydrogel-based transparent subdural electrode with the salt bridge as a bio-friendly interface. References [1] H. Yuk et al., “Hydrogel bioelectronics,” Chemical Society Reviews , 48, 1642–1667 (2019). [2] S. Oribe et al. , “Hydrogel-Based Organic Subdural Electrode with High Conformability to Brain Surface,” Scientific Reports , 9, 1–10 (2019). Figure 1

Abstract: The biomedical measurements such as electrocorticography and electromyography have been widely performed for medical monitoring, diagnosis, and treatment of the diseases. In particular, subdural electrodes directly placed on the surface of a brain have been developed for a treatment of epilepsy and surgery. Conventional subdural electrodes consisting of metal electrodes such as Pt and the silicone-based substrate has various problems; the silicone substrate is not able to completely adhere to the brain surface due to its hardness and hydrophobicity, and artifacts will be generated in MRI imaging due to metal electrodes. We have developed a total organic hydrogel-based subdural electrode by embedding carbon fabric (CF) modified with poly(3,4-ethylenedioxythiophene) (PEDOT) into a poly(vinyl alcohol) (PVA) hydrogel substrate. Their softness similar to the living tissue and conformability to the curved surface of brains enabled easy handling, and the total organic materials will contribute to clearer MRI images without image artifacts. Moreover, molecules can pass through the hydrogel substrate of the electrode. Currently, we are working on the development of a hydrogel salt bridge electrode that is more transparent than conventional and our reported electrodes and reduces adverse effect on the body by avoiding the electrode from the biotissue surface and embedding salt bridges in the hydrogel substrate (Figure 1a). Although silicone microchannel is needed for a separation between hydrogels for the salt bridge and substrate, the bonding strength of silicone and hydrogel is poor, which causes a slip of the electrodes from measuring points. Various techniques for chemical bonding of silicone and hydrogel have been reported [1] [2] , however, some of the substances used in these techniques are toxic and not biocompatible. In this study, we employed a physical bonding method with protrusions which are placed on the silicone surface to reduce the sliding of silicone and hydrogel. A frustum structure was selected as the shape of the protrusion, as for avoiding an exfoliation of the PVA hydrogel substrate from the silicone microchannel (Figure 1a). In order to evaluate the bonding strength, we prepared micro-structured polydimethylsiloxane (PDMS) sheets with 3D printed molds. The various micro-structured PDMS sheets were designed as rectangular (2 mm in the width) and frustum protrusions (4 mm, 2 mm, 1 mm and 0.5 mm in width) (Figure 1b). PDMS sheets with protrusions were embedded in PVA gel (15wt%), which were cross-linked by repeating freezing and thawing cycles (10 min at -30 °C and 10 min at room temperature for three times). A digital force gauge and an electric stand were used to perform tensile tests. Tensile loads were applied to both ends of the specimens, and the tension was recorded until the PDMS sheet and PVA gel were completely separated. In order to apply to the electrocorticography, we prepared the salt bridge electrode combined with the protrusions. The electrode was fabricated by injecting PVA precursor (10wt%) into the PDMS channel with protrusions and embedding that in PVA gel (15wt%). Each PVA was cross-linked by repeating freezing and thawing cycles at the same condition the above experiment. Then the electrode was placed on the brain of a pig along with a conventional electrode, and the brain wave was measured by electrocorticography (ECoG). Among the prepared PDMS sheets, the bonding strength of specimens with frustrum protrusions (10.8 kPa for 2 mm) showed higher than that of specimens with rectangular protrusions (9.3 kPa) and without protrusions (8.0 kPa) (Figure 1c). The bonding strength increased with a decrease of the size (0.5 mm, 2 mm and 4 mm) of protrusions (Figure 1d). Only 1 mm of protrusions did not follow the manner, which was under discussing. These results show that the frustum protrusions contribute to the physical bonding. Finally, we measured the ECoG signal by using the prepared hydrogel electrode. The salt bridge electrode was highly flexible enough to closely contact with the surface of the brain. Moreover, the ECoG signal measured by the hydrogel electrode was followed to conventional electrodes (Figure 1e). In conclusion, we successfully fabricated a flexible and biocompatible subdural electrode. References [1] Q. Liu, G. Nian, C. Yang, S. Qu and Z. Suo, “Bonding dissimilar polymer networks in various manufacturing processes,” Nature Communications, vol. 9, (2018) [2] D. Wirthl, R. Pichler, M. Drack, G. Kettlguber, R. Moser, R. Gerstmayr, F. Hartmann, E. Bradt, R. Kaltseis, C. M. Siket, S. E. Schausberger, S. Hild, S. Bauer and M. Kalten, “Instant tough bonding of hydrogels for soft machines and electronics,” Science Advances, vol. 3, no. 6, (2017). Figure 1

Abstract: The skin is a structure that covers the surface of the body and separates the inside and outside of the body. The stratum corneum on the surface of the skin has a barrier function that prevents the entry of foreign substances and excessive moisture evaporation. It has been reported that impaired barrier function can lead to dryness and diseases of the skin. Therefore, it is important to evaluate the barrier function. Currently, the measurement of transepidermal water loss (TEWL) is used as the main method. The barrier function is evaluated based on the fact that water evaporation increases when barrier function is reduced. This method, however, requires strict temperature and humidity control, and can be used only in designated locations as a result. As another indicator of barrier function, it has been known that the transepidermal potential (TEP), a potential difference in the thickness direction in the epidermis, can be used [1], but there was no practical method to measure it. In this study, we developed a wearable patch-type TEP measurement device that can evaluate barrier function with minimal invasiveness. To measure the TEP, it is necessary to connect electrodes to the inside and outside the epidermis. In order to connect electrodes to the inside the epidermis, we developed a tip-conducting porous microneedle array by insulating except for the tip of a porous microneedle array that is entirely conductive [2]. In order to make the device thinner and more flexible, an Ag/AgCl reference electrode was developed, in which the electrode and liquid junction were screen-printed on a thin film. We then combined a microneedle array and a flexible electrode into a patch-type device. In addition, we are now developing a small voltmeter that can be connected to a patch-type device to make a wearable device for long-term TEP monitoring. First, a tip-conducting porous microneedle array was developed to connect minimally invasively to the interior of the epidermis. The microneedle array was prepared by mixing the monomer solution with the porogen solution, pouring it into a mold and solidifying it with UV light. The microneedle array was placed on a block of Polydimethylsiloxane (PDMS), pressed down with a 10 g weight, and the needle tips were buried in PDMS block while the vapor deposition of the parylene C coating. The porogen was then dissolved in an organic solvent. The distribution of parylene C at the tip of the needle was evaluated by using energy dispersive X-ray spectroscopy (EDX). In addition, the electrical resistance of the microneedle array was measured to evaluate the insulation. Next, a flexible Ag/AgCl reference electrode was developed. Plastic wrapping film was used as a substrate, Ag/AgCl paste was printed by screen printing, and polyvinylpyrrolidone (PVP) gel containing KCl was dripped over it and dried. A waterproof adhesive tape with a 0.1 mm diameter hole was then applied, and a liquid mixture of polyurethane and cellulose acetate dissolved in an organic solvent and KCl powder was applied and dried. The prepared electrode was then immersed in Ringer's solution and the electrode potential was measured for 24 hours to evaluate the deviation of the electrode potential. Then, a patch-type device was fabricated by combining a tip-conducting porous microneedle array with a flexible Ag/AgCl reference electrode. A microneedle array was attached to the electrode using a waterproof adhesive tape. The device was used to measure the TEP of porcine skin samples, and the measured values were evaluated in comparison with the results obtained by the conventional method, which is not practical due to its high invasiveness. The fabricated microneedle array was successfully insulated except for the tip of the needle (Fig. 1A). The deviation of the electrode potential of the fabricated flexible electrodes was less than 5 mV after 24 hours of measurement. The fabricated device was thin and flexible (Fig. 1B). The measured TEP values of the fabricated device were almost consistent with those of the conventional method (Fig. 1C). Furthermore, we are now developing a small wristwatch-type voltmeter. In conclusion, this device could be a wearable device that can monitor TEP minimally invasively and for a long time. References [1] E. Kawai, J. Nakanishi, N. Kumazawa, K. Ozawa, and M. Denda, “Skin surface electric potential as an indicator of skin condition: A new, non-invasive method to evaluate epidermal condition,” Exp. Dermatol. , 17 , 688–692 (2008). [2] K. Nagamine, J. Kubota, H. Kai, Y. Ono, and M. Nishizawa, “An array of porous microneedles for transdermal monitoring of intercellular swelling,” Biomed. Microdevices , 19 , 1–6 (2017) Figure 1

Abstract: Oral drugs administrate to a body with painless and low cost, however, the efficiency of most oral drugs is not high due to the metabolic degradation during adsorption process. In contrast, a skin patch-based transdermal drug delivery is attractive for avoiding the route of metabolic degradation, as well as its painless property. In order to improve the transdermal drug delivery, microneedle array has been of much interest since it can reach inside stratum corneum and enhance the transdermal adsorption of the drugs. Different types of microneedles of the drug-coated, the dissolvable, and the hollowed structure have been applied for skin patches. In the previous study, we have developed porous microneedles (PMN) consisting of glycidyl methacrylate (GMA) by using the porogen method with polyethylene glycol (PEG), which allowed fast water absorption and enough mechanical strength to reach into the skin [1]. Moreover, the GMA-PMN was proved to decrease the transdermal ionic resistance [2] , and thus is expected to enhance the iontophoresis efficiency. However, since the tip of GMA-PMN remained in the body is hard to be metabolized, an adverse effect on the human body could be cased. In this study, we developed PMNs consisting of a biodegradable material, polylactic acid-glycolic acid copolymer (PLGA) (Figure 1A). In order to improve the hydrophilicity and mechanical strength of the PLGA-PMNs, the water-soluble and biodegradable polymer was composited to the PLGA-PMNs. The PMN were fabricated by a combination of molding method and freeze-drying. PLGA dissolved in 1,4-dioxane was filled into a PDMS mold, frozen in a freezing chamber, and dried in a freeze-drying machine. The structure of the PMN chip consists of a substrate (8 mm in the width), the supporting posts (500 µm in diameter, 300 µm in height), and the needles (300 µm in length). The supporting post improves the penetration of the needle into the skin. The pitch between the centers of each needle is 1 mm. The pore size of the fabricated PMN was found to be about 10 µm from SEM images (Figure 1B). The mechanical strength evaluated by a force gauge and a load cell was 0.03 N/needle, which less than the enough strength to penetrate the skin (0.06 N/needle [3]). In order to improve the mechanical strength of the PLGA-PMNs, an aqueous solution of carboxymethyl cellulose (CMC) was filled in the pores of the PLGA-PMNs and dried. The CMC-filled PLGA-PMN showed a higher load-bearing capacity than the PLGA-PMN. By soaking the PMN with saline solution and applying current, the ionic conduction through the PLGA-PMN chip was observed. In addition, the water adsorbing rate of the CMC-filled PLGA-PMN was faster than that of PLGA-PMN. These results indicate the pores of the PMN form continuous channels through the chip, and the CMC improves wettability of the PLGA-PMN due to its high hydrophilicity. In conclusion, we successfully fabricated porous microneedle from biodegradable materials and improved the mechanical strength and hydrophilicity by stuffing the biodegradable polymer, which provides a key role for practical applications. References [1] L. Liu, H. Kai, K. Nagamine, Y. Ogawa, M. Nishizawa, “Porous Polymer Microneedles with Interconnecting microchannels for rapid fluid transport.” RSC Advances 6, 48630-48635, (2016). [2] K. Nagamine, J. Kubota, H. Kai, Y. Ono, M. Nishizawa, “An array of porous microneedles for trans dermal monitoring of intercellular swelling”, Biomed Microdevices , 19, 68, (2017) [3] J.D. Kim, M. Kim, H. Yang, K. Lee, H. Jung, “Droplet-born air blowing: novel dissolving microneedle fabrication.” Control Release , 170(3), 430-436, (2013) Figure 1