Project description:Recently, photodynamic therapy (PDT) which involves a photosensitizer (PS), a special drug activated by light, and light irradiation has been widely used in treating various skin diseases such as port-wine stain as well as cancers such as melanoma and non-melanoma skin cancers. PDT comprises two general steps: the introduction of PS into the body or a specific spot to be treated, and the irradiation process using a light source with a specific wavelength to excite the PS. Although PDT is gaining great attention owing to its potential as a targeted approach in the treatment of skin cancers, several limitations still exist for practical use. One of the biggest challenges is the limited penetration of light owing to scattering, reflection, and absorption of light inside the skin layers. In addition, accidental light exposure of the target area causes additional cellular damage, which causes unexpected complications. To solve these issues, we introduced an optical microneedle-lens array (OMLA) to improve the efficiency and safety of PDT treatment. We designed and fabricated a novel optical microneedle-lens array with controlled dimensions to optimize light transmission. In addition, PS was coated uniformly over the tips of the OMLA using the dip coating method. Finally, we confirmed that the PS coated on the OMLA was released into the target area and subsequently generated radical oxygen by light irradiation. We expect that our proposed OMLA for PDT treatment can realize a new light-transmission platform optimized for PDT with targeting various types of skin cancers.
Project description:We demonstrate the design and integration of droplet-based microfluidic devices with microoptical element arrays for enhanced detection of fluorescent signals. We show that the integration of microlenses and mirror surfaces in these devices results in an 8-fold increase in the fluorescence signal and in improved spatial resolution. Using an array of microlenses, massively parallel detection of droplets containing fluorescent dyes was achieved, leading to detection throughputs of about 2000 droplets per second and per lens, parallelized over 625 measurement points.
Project description:Biopsy is the gold standard for tumor diagnosis, as this technology provides highly detailed and reliable information on tumorigenesis and progression. Resembling the discrete wettability of desert beetles, in this study, a fluorescence polymerase chain reaction (F-PCR) microneedle array (MNA) platform is developed for efficient spatial tumor biopsy. This MNA is fabricated by the coupled strategies of bottom-up self-assembly and top-down photolithography; it comprises a hydrophobic silica nanoparticle-assembled substrate and graphene aerogel-hydrogel hybrid microneedle peaks. Benefitting from the hydrophilicity and absorption capacity of its graphene hybrid microneedle peaks, MNA can easily penetrate tissue specimens and collect tumor nucleic acid biomarkers stereoscopically. In addition, because of the discrete wettability of the platform, both tissue fluids and PCR liquids can be easily removed from the substrate, and each microneedle peak is similar to an independent island for directly conducting F-PCR reactions for tumor marker discovery. Based on these advantages, the F-PCR-MNA platform is demonstrated to be ideal for detecting DNA biomarkers of lung carcinoma in standard solutions, mouse tissue samples, and clinical specimens, thus indicating its practical potential as an innovative tumor biopsy system.
Project description:Successful development of siRNA therapies has significant potential for the treatment of skin conditions (alopecia, allergic skin diseases, hyperpigmentation, psoriasis, skin cancer, pachyonychia congenital) caused by aberrant gene expression. Although hypodermic needles can be used to effectively deliver siRNA through the stratum corneum, the major challenge is that this approach is painful and the effects are restricted to the injection site. Microneedle arrays may represent a better way to deliver siRNAs across the stratum corneum. In this study, we evaluated for the first time the ability of the solid silicon microneedle array for punching holes to deliver cholesterol-modified housekeeping gene (Gapdh) siRNA to the mouse ear skin. Treating the ear with microneedles showed permeation of siRNA in the skin and could reduce Gapdh gene expression up to 66% in the skin without accumulation in the major organs. The results showed that microneedle arrays could effectively deliver siRNA to relevant regions of the skin noninvasively.
Project description:A microneedle array patch (MAP) has been developed as a new delivery system for vaccines. Preclinical and clinical trials with a vaccine MAP showed improved stability, safety, and immunological efficacy compared to conventional vaccine administration. Various vaccines can be delivered with a MAP. Currently, microneedle manufacturers can mass-produce pharmaceutical MAP and cosmetic MAP and this mass-production system can be adapted to produce a vaccine MAP. Clinical trials with a vaccine MAP have shown comparable efficacy with conventional administration, and discussions about regulations for a vaccine MAP are underway. However, there are concerns of reasonable cost, mass production, efficacy, and safety standards that meet FDA approval, as well as the need for feedback regarding the best method of administration. Currently, microneedles have been studied for the delivery of many kinds of vaccines, and preclinical and clinical studies of vaccine microneedles are in progress. For the foreseeable future, some vaccines will continue to be administered with syringes and needles while the use of a vaccine MAP continues to be improved because of the advantages of less pain, self-administration, improved stability, convenience, and safety.
Project description:The successful application of lasers in the treatment of skin diseases and cosmetic surgery is largely based on the principle of conventional selective photothermolysis which relies strongly on the difference in the absorption between the therapeutic target and its surroundings. However, when the differentiation in absorption is not sufficient, collateral damage would occur due to indiscriminate and nonspecific tissue heating. To deal with such cases, we introduce a novel spatially selective photothermolysis method based on multiphoton absorption in which the radiant energy of a tightly focused near-infrared femtosecond laser beam can be directed spatially by aiming the laser focal point to the target of interest. We construct a multimodal optical microscope to perform and monitor the spatially selective photothermolysis. We demonstrate that precise alteration of the targeted tissue is achieved while leaving surrounding tissue intact by choosing appropriate femtosecond laser exposure with multimodal optical microscopy monitoring in real time.
Project description:Pulsed dye laser (PDL) is the gold standard for treatment of port-wine stain (PWS) birthmarks but multiple treatments are required and complete resolution is often not achieved. Posttreatment vessel recurrence is thought to be a factor that limits efficacy of PDL treatment of PWS. Imiquimod 5% cream is an immunomodulator with antiangiogenic effects.We sought to determine if application of imiquimod 5% cream after PDL improves treatment outcome.Healthy individuals with PWS (n = 24) were treated with PDL and then randomized to apply posttreatment placebo or imiquimod 5% cream for 8 weeks. Chromameter measurements (Commission Internationale de l'Eclairage L?a?b? colorspace) for 57 PWS sites (multiple sites per patient) were taken at baseline and compared with measurements taken 8 weeks posttreatment. The ?a? (change in erythema) and ?E (difference in color between normal-appearing skin and PWS skin) were measured to quantify treatment outcome.Two patients developed minor skin irritation. Other adverse effects were not noted. Average ?a? was 0.43 for PDL + placebo sites (n = 25) and 1.27 for PDL + imiquimod sites (n = 32) (P value = .0294) indicating a greater reduction in erythema with imiquimod. Average ?E was 2.59 for PDL + placebo and 4.08 for PDL + imiquimod (P value = .0363), again indicating a greater color improvement with imiquimod.Effects were evaluated after a single treatment and duration of effect is unknown.Combined selective photothermolysis and antiangiogenic therapy may enhance PWS treatment efficacy.
Project description:Highly reliable signal recording with low electrode-skin impedance makes the microneedle array electrode (MAE) a promising candidate for biosignal sensing. However, when used in long-term health monitoring for some incidental diseases, flexible microneedles with perfectly skin-tight fit substrates lead to sweat accumulation inside, which will not only affect the signal output but also trigger some skin allergic reactions. In this paper, a flexible MAE on a Miura-ori structured substrate is proposed and fabricated with two-directional in-plane bendability. The results from the comparison tests show enhanced performance in terms of (1) the device reliability by resisting peeling off of the metal layer from the substrate during the operation and (2) air ventilation, achieved from the air-circulating channels, to remove sweat. Bio-signal recordings of electrocardiography (ECG), as well as electromyography (EMG) of the biceps brachii, in both static and dynamic states, are successfully demonstrated with superior accuracy and long-term stability, demonstrating the great potential in health monitoring applications.
Project description:The development of a microneedle-based biosensor array for multiplexed in situ detection of exercise-induced metabolic acidosis, tumor microenvironment, and other variations in tissue chemistry is described. Simultaneous and selective amperometric detection of pH, glucose, and lactate over a range of physiologically relevant concentrations in complex media is demonstrated. Furthermore, materials modified with a cell-resistant (Lipidure(®)) coating were shown to inhibit macrophage adhesion; no signs of coating delamination were noted over a 48-h period.
Project description:A microneedle array is an attractive option for a minimally invasive means to break through the skin barrier for efficient transdermal drug delivery. Here, we report the applications of solid polymer-based ion-conductive porous microneedles (PMN) containing interconnected micropores for improving iontophoresis, which is a technique of enhancing transdermal molecular transport by a direct current through the skin. The PMN modified with a charged hydrogel brings three innovative advantages in iontophoresis at once: (1) lowering the transdermal resistance by low-invasive puncture of the highly resistive stratum corneum, (2) transporting of larger molecules through the interconnected micropores, and (3) generating electroosmotic flow (EOF). In particular, the PMN-generated EOF greatly enhances the transdermal molecular penetration or extraction, similarly to the flow induced by external pressure. The enhanced efficiencies of the EOF-assisted delivery of a model drug (dextran) and of the extraction of glucose are demonstrated using a pig skin sample. Furthermore, the powering of the PMN-based transdermal EOF system by a built-in enzymatic biobattery (fructose / O2 battery) is also demonstrated as a possible totally organic iontophoresis patch.