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The need for hollow microneedle arrays is important for both drug delivery and wearable sensor applications; however, their fabrication poses many challenges. Hollow metal microneedle arrays residing on a flexible metal foil substrate were created by combining additive manufacturing, micromolding, and electroplating approaches in a process we refer to as electromolding. A solid microneedle with inward facing ledge was fabricated with a two photon polymerization (2PP) system utilizing laser direct write (LDW) and then molded with polydimethylsiloxane. These molds were then coated with a seed layer of Ti/Au and subsequently electroplated with pulsed deposition to create hollow microneedles. An inward facing ledge provided a physical blocking platform to restrict deposition of the metal seed layer for creation of the microneedle bore. Various ledge sizes were tested and showed that the resulting seed layer void could be controlled via the ledge length. Mechanical properties of the PDMS mold was adjusted via the precursor ratio to create a more ductile mold that eliminated tip damage to the microneedles upon removal from the molds. Master structures were capable of being molded numerous times and molds were able to be reused. SEM/EDX analysis showed that trace amounts of the PDMS mold were transferred to the metal microneedle upon removal. The microneedle substrate showed a degree of flexibility that withstood over 100 cycles of bending from side to side without damaging. Microneedles were tested for their fracture strength and were capable of puncturing porcine skin and injecting a dye.

Recently microneedles have been explored for transdermal monitoring of biomarkers with the goal to achieve time-sensitive clinical information for routine point-of-care health monitoring. In this highlight we provide a general overview of recent progress in microneedle-based sensing research, including: (a) glucose monitoring, (b) ex vitro microneedle diagnostic systems for general health monitoring with an emphasis on sensor construction, and (c) in vivo use of microneedle sensors.

Interstitial fluid (ISF) has recently garnered interest as a biological fluid that could be used as an alternate to blood for biomedical applications, diagnosis, and therapy. ISF extraction techniques are promising because they are less invasive and less painful than venipuncture. ISF is an alternative, incompletely characterized source of physiological data. Here, we describe a novel method of ISF extraction in rats, using microneedle arrays, which provides volumes of ISF that are sufficient for downstream analysis techniques such as proteomics, genomics, and extracellular vesicle purification and analysis. This method is potentially less invasive than previously reported techniques. The limited invasiveness and larger volumes of extracted ISF afforded by this microneedle-assisted ISF extraction method provide a technique that is less stressful and more humane to laboratory animals, while also allowing for a reduction in the numbers of animals needed to acquire sufficient volumes of ISF for biomedical analysis and application.

When attempting to integrate single-molecule fluorescence microscopy with microfabricated devices such as microfluidic channels, fabrication constraints may prevent using traditional coverslips. Instead, the fabricated devices may require imaging through material with a different thickness or index of refraction. Altering either can easily reduce the quality of the image formation (measured by the Strehl ratio) by a factor of 2 or more, reducing the signal-to-noise ratio accordingly. In such cases, successful detection of single-molecule fluorescence may prove difficult or impossible. Here we provide software to calculate the effect of non-design materials upon the Strehl ratio or ensquared energy and explore the impact of common materials used in microfabrication.

Next generation pulsed power (NGPP) machines and accelerators require a better understanding of the materials used within the vacuum vessels to achieve lower base pressures (P << 10−5 Torr) and reduce the overall contaminant inventory while incorporating various dielectric materials which tend to be unfavorable for ultra-high vacuum (UHV) applications. By improving the baseline vacuum, it may be possible to delay the onset of impedance collapse, reduce current loss on multi-mega Amp devices, or improve the lifetime of thermionic cathodes, etc [3]. In this study, we examine the vacuum outgassing rate of Rexolite® (cross-linked polystyrene) and Kel-F® (polychlorotrifluoroethylene) as candidate materials for vacuum insulators [1]. These values are then incorporated into boundary conditions for molecular flow simulations using COMSOL Multiphysics® and used to predict the performance of a prototypical pulsed power system designed for 10−8 Torr operations.

Real-time monitoring of an individual’s physiologic state without constant observation by a healthcare professional necessitates the construction of an autonomous remote diagnostic device that is capable of performing a wide range of diagnostic functions. For many applications, assessing the immediate physiologic state of an individual as he or she is continuously exposed to diverse environments would require complex dynamic chemical processing scenarios that are capable of real time readouts. We seek to answer these problems by combining in vivo microneedle platforms with multifunctional lab-on-chip electrode arrays that are capable of detecting a wide variety of relevant biomarkers. The results presented here provide an important proof-of-concept demonstration of integration of microneedles with a microchip platform containing fluidic channels and electrode transducers. As shown by immunoassay detection of myoglobin and troponin, such a device may be used to extract interstitial fluid and monitor biologically important molecules.

Dermal interstitial fluid (ISF) is an underutilized information-rich biofluid potentially useful in health status monitoring applications whose contents remain challenging to characterize. Here, we present a facile microneedle approach for dermal ISF extraction with minimal pain and no blistering for human subjects and rats. Extracted ISF volumes were sufficient for determining transcriptome, and proteome signatures. We noted similar profiles in ISF, serum, and plasma samples, suggesting that ISF can be a proxy for direct blood sampling. Dynamic changes in RNA-seq were recorded in ISF from induced hypoxia conditions. Finally, we report the first isolation and characterization, to our knowledge, of exosomes from dermal ISF. The ISF exosome concentration is 12–13 times more enriched when compared to plasma and serum and represents a previously unexplored biofluid for exosome isolation. This minimally invasive extraction approach can enable mechanistic studies of ISF and demonstrates the potential of ISF for real-time health monitoring applications., Philip Miller et al. present an approach for extracting dermal interstitial fluid (ISF) using an array of hollow microneedles in a cylindrical substrate that minimizes skin compression and tissue damage. They extract larger volumes of ISF suitable for downstream analyses, compared to previous reports.

Electroplated iron was investigated as a novel material for microneedle fabrication due to its recent success as a biocompatible metal in other medical device applications. Hollow polymer microneedles were made using a laser direct write process that involved two-photon polymerization of a commercially available Class 2a biocompatible polymer and subsequent electroplating of this structure with iron. Electroplating bath and deposition conditions were shown to affect the mechanical properties of both iron plated microneedles and iron plated on planar polymer substrates. Conditions for depositing the iron coatings were investigated in terms of grain size, residual strain, and elemental composition for planar iron samples. Fracture strength and puncture mechanics into ex vivo porcine skin for iron coated hollow microneedles were examined. Biocompatibility testing was performed using the MTT assay against human epidermal keratinocytes with several concentrations of iron extract to investigate iron as a material used for transdermal applications. Iron coatings proved to significantly improve the strength of the hollow polymer microneedles and sustained structural integrity up to 7 insertions into porcine skin without bending. A commercially available device (Medtronic MiniMed Quick-Serter®) was used for controlled application of microneedles into porcine skin and estimations of insertion forces for the device were made. Plating conditions were optimized such that an adherent, uniform, and high purity iron coating was deposited onto polymer substrates and polymer microneedles without delamination or fracturing of the microneedles upon ex vivo insertion into porcine skin.

Microneedles are minimally invasive transdermal medical devices that are utilized for various applications, including drug delivery, fluid sampling, micro-dialysis, and electrochemical sensing. These devices are associated with less pain and tissue damage as compared with conventional hypodermic needle-based devices. In this study, we demonstrate fabrication of titanium alloy microneedle arrays with nitrogen-incorporated ultrananocrystalline diamond (N-UNCD) coatings. Microneedles were micromachined from ASTM F136 ELI Ti –6Al–4V alloy, a widely used medical-grade titanium alloy. N-UNCD coatings were deposited on the microneedles using microwave plasma enhanced chemical vapor deposition to enhance mechanical strength, increase hardness, improve biocompatibility, and provide an electrochemically stable surface. The structural and chemical properties of the N-UNCD titanium alloy microneedle arrays were evaluated using scanning electron microscopy and Raman spectroscopy. The mechanical robustness and skin penetration capability of the devices were demonstrated using cadaveric porcine skin. Finally, the electrochemical properties of the N-UNCD electrodes were evaluated; in vitro electrochemical detection of uric acid and dopamine was demonstrated using unmodified N-UNCD electrodes. These results demonstrate the application potential of N-UNCD-coated titanium alloy microneedles for transdermal electrochemical biosensing applications.

A microneedle-based self-powered biofuel-cell glucose sensor is described. The biofuel cell sensor makes use of the integration of modified carbon pastes into hollow microneedle devices. The system displays defined dependence of the power density vs glucose concentration in artificial interstitialfluid. An excellent selectivity against common electroactive interferences and long-term stability are obtained. The attractive performance of the device indicates considerable promise for subdermal glucose monitoring. Keywords: Microneedle array, Glucose, Self-powered sensor, Biofuel cell

Miconazole is an imidazole used for treatment of fungal infections that exhibits poor solubility in polar solvents (e.g., aqueous solutions). Microneedles, small-scale lancet-shaped devices that are commonly used for delivery of pharmacologic agents and vaccines, were made out of an acid anhydride copolymer using visible light dynamic mask micro-stereolithography/micromolding and loaded with miconazole using a piezoelectric inkjet printer. The miconazole-coated microneedles showed biodegradation and antifungal activity against the organism Candida albicans (ATCC 90028) on Sabouraud dextrose agar using an in vitro agar plating method. The results of this study demonstrate that piezoelectric inkjet printing may be used load microneedles and other drug delivery devices with pharmacologic agents. Miconazole-loaded microneedles prepared by the visible light dynamic mask micro-stereolithography–micromolding–piezoelectric inkjet printing approach have potential use in transdermal treatment of cutaneous fungal infections.

The determination of electrolytes is invaluable for point of care diagnostic applications. An ion selective transdermal microneedle sensor is demonstrated for potassium by integrating a hollow microneedle with a microfluidic chip to extract fluid through a channel towards a downstream solid-state ion-selective-electrode (ISE). 3D porous carbon and 3D porous graphene electrodes, made via interference lithography, are compared as solid-state transducers for ISE's and evaluated for electrochemical performance, stability, and selectivity. The porous carbon K(+) ISE's show better performance than the porous graphene K(+) ISE's, capable of measuring potassium across normal physiological concentrations in the presence of interfering ions with greater stability. This new microfluidic/microneedle platform shows promise for medical applications.

The delivery of amphotericin B, a pharmacologic agent with activity against a broad spectrum of fungi as well as against parasitic protozoa, has been complicated by the fact that amphotericin B exhibits poor solubility in aqueous solutions at physiologic pH levels. In this study, piezoelectric inkjet printing was used to modify the surfaces of Gantrez 169 BF microneedles (Ashland, Covington, KY). These amphotericin B-loaded microneedles demonstrated activity against Candida parapsilosis in a radial diffusion assay. The results of this study suggest that a combination of visible light dynamic mask microstereolithography, micromolding, and piezoelectric inkjet printing may be used to prepare amphotericin B-loaded microneedles with antifungal properties. It is envisioned that microneedles containing amphotericin B may be used for transdermal delivery of pharmacologic agents for the treatment of cutaneous fungal infections as well as cutaneous leishmaniasis.

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.

We report on the development of a microneedle-based multiplexed drug delivery actuator that enables the controlled delivery of multiple therapeutic agents. Two individually addressable channels on a single microneedle array, each paired with its own reservoir and conducting polymer nanoactuator, are used to deliver various permutations of two unique chemical species. Upon application of suitable redox potentials to the selected actuator, the conducting polymer is able to undergo reversible volume changes, thereby serving to release a model chemical agent in a controlled fashion through the corresponding microneedle channels. Time-lapse videos offer direct visualization and characterization of the membrane switching capability and, along with calibration investigations, confirm the ability of the device to alternate the delivery of multiple reagents from individual microneedles of the array with higher precision and temporal resolution than conventional drug delivery actuators. Analytical modeling offers prediction of the volumetric flow rate through a single microneedle and accordingly can be used to assist in the design of subsequent microneedle arrays. The robust solid-state design and lack of mechanical components circumvent reliability issues that challenge fragile conventional microelectromechanical drug delivery devices. This proof-of-concept study demonstrates the potential of the drug delivery actuator system to aid in the rapid administration of multiple therapeutic agents and indicates the potential to counteract diverse biomedical conditions.

This article describes the design of a new and attractive minimally-invasive bicomponent microneedle sensing device for the electrochemical monitoring of the excitatory neurotransmitter glutamate and glucose. The new device architecture relies on the close integration of solid and hollow microneedles into a single biosensor array device containing multiple microcavities. Such microcavities facilitate the electropolymeric entrapment of the recognition enzyme within each microrecess. The resulting microneedle biosensor array can be employed as a minimally-invasive on-body transdermal patch, obviating the extraction/sampling of the biological fluid, thereby simplifying device requirements. The new concept is demonstrated for the electropolymeric entrapment of glutamate oxidase and glucose oxidase within a poly(o-phenylenediamine) (PPD) thin film. The PPD-based enzyme entrapment methodology enables the effective rejection of coexisting electroactive interferents without compromising the sensitivity or response time of the device. The resulting microneedle-based glutamate and glucose biosensors thus exhibit high selectivity, sensitivity, speed, and stability in both buffer and undiluted human serum. High-fidelity glutamate measurements down to the 10 µM level are obtained in serum. The attractive recess design also serves to protect the enzyme layer upon insertion into the skin. This simple, yet robust microneedle design is well-suited for diverse biosensing applications in which real-time metabolite monitoring is a core requirement.

Microneedles are small-scale needle-like projections that may be used for transdermal delivery of pharmacologic agents, including protein-containing and nucleic acid-containing agents. Commercial translation of polymeric microneedles would benefit from the use of facile and cost effective fabrication methods. In this study, visible light dynamic mask microstereolithography, a rapid prototyping technique that utilizes digital light projection for selective polymerization of a liquid resin, was used for fabrication of solid microneedle array structures out of an acrylate-based polymer. Pulsed laser deposition was used to deposit silver and zinc oxide coatings on the surfaces of the visible light dynamic mask microstereolithography-fabricated microneedle array structures. Agar diffusion studies were used to demonstrate the antimicrobial activity of the coated microneedle array structures. This study indicates that light-based technologies, including visible light dynamic mask microstereolithography and pulsed laser deposition, may be used to fabricate microneedles with antimicrobial properties for treatment of local skin infections.

We report on thin film deposition of poly(1,3-bis-(p-carboxyphenoxy propane)-co-sebacic anhydride)) 20:80 thin films containing several gentamicin concentrations by matrix assisted pulsed laser evaporation (MAPLE). A pulsed KrF* excimer laser was used to deposit the polymer–drug composite thin films. Release of gentamicin from these MAPLE-deposited polymer conjugate structures was assessed. Fourier transform infrared spectroscopy was used to demonstrate that the functional groups of the MAPLE-transferred materials were not changed by the deposition process nor were new functional groups formed. Scanning electron microscopy confirmed that MAPLE may be used to fabricate thin films of good morphological quality. The activity of gentamicin-doped films against Escherichia coli and Staphylococcus aureus bacteria was demonstrated using disk diffusion and antibacterial drop test. Our studies indicate that deposition of polymer–drug composite thin films prepared by MAPLE is a suitable technique for performing controlled drug delivery. Antimicrobial thin film coatings have several medical applications, including use for indwelling catheters and implanted medical devices.

Surgeons and patients are demanding improved replacements for dysfunctional ossicular bones. Replacement of the entire ossicular chain and positioning the prosthesis between the stapes footplate and the tympanic membrane are of particular challenges. Many materials have been used since the first ossicular replacement; at the present time, the two most widely used materials are titanium and hydroxyapatite. Studies have indicated little difference between these two materials. A variety of novel additions have been added to total ossicular replacement prostheses to overcome limitations associated with conventional prostheses. Testing of novel prosthesis materials and designs over long time intervals is needed in order to validate and expand their usage.

Laser micromachining is becoming a common method for fabrication of microstructured medical devices. Developments in pulsed laser technology have made it possible to achieve precision machining of sub-micrometer features with minimal damage to the surrounding material. Several aspects of laser micromachining, including machining methods, types of lasers used in micromachining, and laser-material interaction, are discussed in this article. Biomedical applications of laser micromachining are also reviewed. The ablation behavior of silicon was examined as a function of laser energy, aperture, and repetition rate. In vitro studies showed that microscale grooves on silicon substrates may be used to orient human aortic vascular smooth muscle cells. We anticipate that the use of laser micromachining for modifying medical and dental devices will become more significant over the coming years.

Sandia National Laboratories will provide technical assistance, within time and budget, to Requester on testing and analyzing a microneedle-based electrolyte sensing platform. Hollow microneedles will be fabricated at Sandia and integrated with a fluidic chip using plastic laminate prototyping technology available at Sandia. In connection with commercial ion selective electrodes the sensing platform will be tested for detection of electrolytes (sodium and/or potassium) within physiological relevant concent ration ranges.

We report on thin film deposition by matrix assisted pulsed laser evaporation (MAPLE) of two polymer–drug composite thin film systems. A pulsed KrF* excimer laser source ( λ = 248 nm, τ = 25 ns, ν = 10 Hz) was used to deposit composite thin films of poly( d , l -lactide) (PDLLA) containing several gentamicin concentrations. FTIR spectroscopy was used to demonstrate that MAPLE-transferred materials exhibited chemical structures similar to those of drop cast materials. Scanning electron microscopy data indicated that MAPLE may be used to fabricate thin films of good morphological quality. The activity of PDLLA–gentamicin composite thin films against Staphylococcus aureus bacteria was demonstrated using drop testing. The influence of drug concentration on microbial viability was also assessed. Our studies indicate that polymer–drug composite thin films prepared by MAPLE may be used to impart antimicrobial activity to implants, medical devices, and other contact surfaces.

The development of a minimally invasive multiplexed monitoring system for rapid analysis of biologically-relevant molecules could offer individuals suffering from chronic medical conditions facile assessment of their immediate physiological state. Furthermore, it could serve as a research tool for analysis of complex, multifactorial medical conditions. In order for such a multianalyte sensor to be realized, it must be minimally invasive, sampling of interstitial fluid must occur without pain or harm to the user, and analysis must be rapid as well as selective. Initially developed for pain-free drug delivery, microneedles have been used to deliver vaccines and pharmacologic agents (e.g., insulin) through the skin.1-2 Since these devices access the interstitial space, microneedles that are integrated with microelectrodes can be used as transdermal electrochemical sensors. Selective detection of glucose, glutamate, lactate, hydrogen peroxide, and ascorbic acid has been demonstrated using integrated microneedle-electrode devices with carbon fibers, modified carbon pastes, and platinum-coated polymer microneedles serving as transducing elements.3-7,8 This microneedle sensor technology has enabled a novel and sophisticated analytical approach for in situ and simultaneous detection of multiple analytes. Multiplexing offers the possibility of monitoring complex microenvironments, which are otherwise difficult to characterize in a rapid and minimally invasive manner. For example, this technology could be utilized for simultaneous monitoring of extracellular levels of, glucose, lactate and pH,9 which are important metabolic indicators of disease states7,10-14 (e.g., cancer proliferation) and exercise-induced acidosis.15

Electrospun scaffolds have been used extensively for tissue engineering applications due to the simple processing scheme and versatility. However, many additional benefits can be imparted to these materials via post-processing techniques. Specifically the addition of structured pores on the micro-scale can offer a method to enable patterned cell adhesion, enhanced diffusional properties, and/or guide vascular infiltration upon implantation in vivo. In this study, we laser ablated electrospun poly(L: -lactic acid) (PLA) scaffolds and assessed the ablation process and cellular interaction by examining human adipose-derived stem cell (hASC) viability and proliferation on laser micro-machined scaffolds. Laser ablated pores of 150, 300, and 600 μm diameter were micro-machined through electrospun PLA scaffolds. Laser ablation parameters were varied and it was determined that the aperture and z-travel direction of the laser linearly correlated with the ablated pore diameter. To assess cytocompatibility of the micro-machined scaffolds, hASCs were seeded on each scaffold and cell viability was assessed on day 7. Human ASCs were able to adhere around the micro-machined features. DNA content was quantified on all scaffolds and it was determined that hASCs were able to proliferate on all scaffolds. The process of laser ablation could impart many beneficial features to electrospun scaffolds by increasing mass transport and mimicking micro-scale features and assisting in patterning of cells around micro-machined features.

Due to their ability to serve as fluorophores and drug delivery vehicles, quantum dots are a powerful tool for theranostics-based clinical applications. In this study, microneedle devices for transdermal drug delivery were fabricated by means of two-photon polymerization of an acrylate-based polymer. We examined proliferation of cells on this polymer using neonatal human epidermal keratinocytes and human dermal fibroblasts. The microneedle device was used to inject quantum dots into porcine skin; imaging of the quantum dots was performed using multiphoton microscopy.

In this study, carbon fiber electrodes were incorporated within a hollow microneedle array, which was fabricated using a digital micromirror device-based stereolithography instrument. Cell proliferation on the acrylate-based polymer used in microneedle fabrication was examined with human dermal fibroblasts and neonatal human epidermal keratinocytes. Studies involving full-thickness cadaveric porcine skin and trypan blue dye demonstrated that the hollow microneedles remained intact after puncturing the outermost layer of cadaveric porcine skin. The carbon fibers underwent chemical modification in order to enable detection of hydrogen peroxide and ascorbic acid; electrochemical measurements were demonstrated using integrated electrode-hollow microneedle devices.

Electrospun scaffolds have been studied extensively for their potential use in bone tissue engineering applications. However, inherent issues with the electrospinning approach limit the thickness of these scaffolds and constrain their use for repair of critical-sized bone defects. One method to increase overall scaffold thickness is to bond multiple electrospun scaffolds together with a biocompatible gel. The objective of this study was to determine whether multiple human adipose-derived stem cell (hASC-seeded electrospun, nanofibrous scaffolds could be layered via in situ collagen assembly and whether the addition of laser-ablated micron-sized pores within the electrospun scaffold layers was beneficial to the bonding process. Pores were created by a laser ablation technique. We hypothesized that the addition of micron-sized pores within the electrospun scaffolds would encourage collagen integration between scaffold layers, and promote osteogenic differentiation of hASCs seeded within the layered electrospun scaffolds. To evaluate the benefit of assembled scaffolds with and without engineered pores, hASCs were seeded on individual electrospun scaffolds, hASC-seeded scaffolds were bonded with type I collagen, and the assembled ∼3-mm-thick constructs were cultured for 3 weeks to examine their potential as bone tissue engineering scaffolds. Assembled electrospun scaffolds/collagen gel constructs using electrospun scaffolds with pores resulted in enhanced hASC viability, proliferation, and mineralization of the scaffolds after 3 weeks in vitro compared to constructs using electrospun scaffolds without pores. Scanning electron microscopy and histological examination revealed that the assembled constructs that included laser-ablated electrospun scaffolds were able to maintain a contracted structure and were not delaminated, unlike assembled constructs containing nonablated electrospun scaffolds. This is the first study to show that the introduction of engineered pores in electrospun scaffolds assists with multilayered scaffold integration, resulting in thick constructs potentially suitable for use as scaffolds for bone tissue engineering or repair of critical bone defects.

Microneedles are needle-like projections with microscale features that may be used for transdermal delivery of a variety of pharmacologic agents, including antibacterial agents. In the study described in this paper, an indirect rapid prototyping approach involving a combination of visible light dynamic mask micro-stereolithography and micromolding was used to prepare microneedle arrays out of a biodegradable acid anhydride copolymer, Gantrez(®) AN 169 BF. Fourier transform infrared spectroscopy, energy dispersive x-ray spectrometry and nanoindentation studies were performed to evaluate the chemical and mechanical properties of the Gantrez(®) AN 169 BF material. Agar plating studies were used to evaluate the in vitro antimicrobial performance of these arrays against Bacillus subtilis, Candida albicans, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Large zones of growth inhibition were noted for Escherichia coli, S. aureus, Enterococcus faecalis and B. subtilis. The performance of Gantrez(®) AN 169 BF against several bacteria suggests that biodegradable acid anhydride copolymer microneedle arrays prepared using visible light dynamic mask micro-stereolithography micromolding may be useful for treating a variety of skin infections.

In this study, biodegradable acid anhydride copolymer microneedles containing quantum dots were fabricated by means of visible light dynamic mask micro-stereolithography-micromolding and inkjet printing. Nanoindentation was performed to obtain the hardness and the Young's modulus of the biodegradable acid anhydride copolymer. Imaging of quantum dots within porcine skin was accomplished by means of multiphoton microscopy. Our results suggest that the combination of visible light dynamic mask micro-stereolithography-micromolding and inkjet printing enables fabrication of solid biodegradable microneedles with a wide range of geometries as well as a wide range of pharmacologic agent compositions.

The design and characterization of a microneedle array-based carbon paste electrode towards minimally invasive electrochemical sensing are described. Arrays consisting of 3 × 3 pyramidal microneedle structures, each with an opening of 425 µm, were loaded with a metallized carbon paste transducer. The renewable nature of carbon paste electrodes enables the convenient packing of hollow non-planar microneedles with pastes that contain assorted catalysts and biocatalysts. Smoothing the surface results in good microelectrode-to-microelectrode uniformity. Optical and scanning electron micrographs shed useful insights into the surface morphology at the microneedle apertures. The attractive performance of the novel microneedle electrode arrays is illustrated in vitro for the low-potential detection of hydrogen peroxide at rhodium-dispersed carbon paste microneedles and for lactate biosensing by the inclusion of lactate oxidase in the metallized carbon paste matrix. Highly repeatable sensing is observed following consecutive cycles of packing/unpacking the carbon paste. The operational stability of the array is demonstrated as well as the interference-free detection of lactate in the presence of physiologically relevant levels of ascorbic acid, uric acid, and acetaminophen. Upon addressing the biofouling effects associated with on-body sensing, the microneedle carbon paste platform would be attractive for the subcutaneous electrochemical monitoring of a number of physiologically relevant analytes.

The fabrication of defined surface topographies and three-dimensional structures is a challenging process for various applications, e.g. in photonics and biomedicine. Laser-based technologies provide a promising approach for the production of such structures. The advantages of femtosecond laser ablation and two-photon polymerization for microstructuring are well known. However, these methods cannot be applied to all materials and are limited by their high cost and long production time. In this study, biomedical applications of an indirect rapid prototyping, molding microreplication of laser-fabricated two- and three-dimensional structures are examined. We demonstrate that by this method any laser-generated surface topography as well as three-dimensional structures can be replicated in various materials without losing the original geometry. The replication into multiple copies enables fast and perfect reproducibility of original microstructures for investigations of cell–surface interactions. Compared to unstructured materials, we observe that microstructures have strong influence on morphology and localization of fibroblasts, whereas neuroblastoma cells are not negatively affected.

This paper gives an overview of the techniques and processes used to protect or ‘harden’ electronic equipment against the effects of the Nuclear Electromagnetic Pulse (EMP). Working from an engineering viewpoint, it not only considers how the threat operates and why it is a threat, but also it considers the measures that can be used to counter the threat andwhat these measures are attempting to achieve. Throughout it is stressed that once the decisionto harden a new piece of equipment is taken, the effects of EMP must be considered during all stages of its development. The paper is then concluded with a list of the typical activities that this might entail.

Endemic cretinism in the adult is often accompanied by a variety of skeletal malformations. The victims of this disorder characteristically exhibit poor posture, with the head inclined forward and with the hips, knees and ankles maintained in partial flexion. 1 Their gait is such as to give the observer an impression of marked instability. One of the factors contributing to the instability is the disturbance of the mechanics of pelvic support resulting from relaxation of the pelvitrochanteric musculature. This in turn arises from the presence of coxa vara, a deformity which is frequently encountered in cretins. 2 The osseous changes appearing in children and resulting in the development of coxa vara in cretins have received scant attention. But few reports on the subject have appeared and these have been limited to the Swiss and German literature. In them the authors have described the occurrence of a disease of the hip