Additive manufacturing of inorganic-organic hybrid materials for transdermal biosensor applications

Two photon polymerization offers many advantages over conventional processes for scalable mass production of medical devices, particularly those with small-scale features. First, the raw materials (e.g., inorganic-organic hybrid materials and acrylate-based polymers) used in two photon polymerization are inexpensive and are widely available. Second, two photon polymerization can be established in a conventional “dirty” manufacturing environment; no cleanroom facilities are required. Third, two photon polymerization is a straightforward and single-step process for creating complex structures with small-scale features. In previous work, two photon polymerization was shown to be able to create microneedles with a larger range of shapes and dimensions than conventional microneedle fabrication techniques [1]. For example, 500-700 micrometer tall microneedles were created out of an acrylate-based polymer that is used in Class IIa medical devices (e.g., hearing aid shells) (Figure 1 (a) and Figure 1 (b)) [1]. A hollow microneedle was used to create pores in the outermost layer of cadaveric porcine skin; a microneedle-generated pore was shown to facilitate delivery of carboxyl quantum dots to the deep epidermis and dermis layers of the cadaveric porcine skin within fifteen minutes. We have prepared several types of hollow microneedle-based biosensors using microneedles that were fabricated using either two photon polymerization or digital micromirror device-based stereolithography. In these biosensors, the sensing mechanisms are located within the bores of the microneedles. For example, we have examined incorporating carbon fiber electrodes within a hollow microneedle array, which was created using a digital micromirror device-based stereolithography instrument [2]. Studies involving trypan blue dye demonstrated that the microneedles remained intact after they punctured the outermost layer of cadaveric porcine skin. The carbon fibers were chemically modified to allow for the detection of hydrogen peroxide and ascorbic acid; the performance of the microneedle-based sensors was demonstrated using electrochemical measurements. In another study, we prepared a multiplexed microneedle-based biosensor array for simultaneous and selective amperometric detection of lactate, glucose, and pH over physiologically relevant analyte levels in complex media (Figure 1c) [3]. In another study, a solid-state ion selective electrode for potassium ions was prepared from three-dimensional porous carbon [4]. This electrode was integrated with a hollow microneedle that was created using two photon polymerization. The functionality of the ion selective electrode was demonstrated over the physiologic range of potassium and in the presence of interfering sodium ions. Please click Additional Files below to see the full abstract

Laser-based three-dimensional printing of zirconium oxide hybrid materials

We have recently examined use of an additive manufacturing approach known as two-photon polymerization to create structures out of zirconium oxide hybrid materials for medical device applications. Two photon polymerization involves processing of a structure with sub-microscale features in an additive manner directly from a computer-generated model. In two-photon polymerization, a femtosecond laser beam is focused within a small volume in a near infrared light-transparent photosensitive material; nearly simultaneous absorption of two photons within a small volume in the photosensitive material results in polymerization and hardening of the material. Because of the quadratic dependence of two-photon absorption probability on intensity, photopolymerization occurs in a localized volume. The energy associated with two photon absorption of infrared photons is analogous to the energy associated with a single photon in the ultraviolet light region of the electromagnetic spectrum. The unit volume of material polymerized using two-photon polymerization is known as a voxel (volumetric pixel). The minimum size of the features obtained in a two-photon polymerization-fabricated structure is related to the voxel-voxel distance, the photosensitivity of the material, the numerical aperture of the objective lens, the exposure time, and the laser power. Titanium:sapphire femtosecond lasers are used in two photon polymerization since these lasers produce high energy intensity in the focal volume due to their short pulse width and high peak power. A medically-relevant structure with an arbitrary geometry may be created using two photon polymerization by polymerizing the material along the laser trace, which is translated in three dimensions via a micropositioning system. Two photon polymerization exhibits advantages over conventional mechanisms for scalable production of small-scale medical devices. Several classes of inexpensive inorganic-organic hybrid materials, polymers, and other photosensitive materials may be fabricated via two photon polymerization. Two photon polymerization can be set up in a conventional environment; no specialized facilities (e.g., cleanroom facilities) are needed. In comparison with conventional multiple-step medical device processing techniques, two photon polymerization is a rapid, straightforward, single-step process. Two photon polymerization was used to create scaffolds for tissue engineering with linear designs in a layer-by-layer manner out of a zirconium oxide hybrid material. Good feature-to-feature uniformity within the scaffolds. In vitro cell studies were used to examine cell-scaffold interactions over time

Refractive effects in pulsar scintillation

Recent studies have focused attention on the refractive effects of long-wavelength (≲ 10^(14) cm) electron density fluctuations in the interstellar medium upon radio observations of pulsars and compact extragalactic radio sources. In earlier work, a simple scattering model was introduced which allowed us to compute fluctuations in mean intensity, image size, pulse width and pulse arrival time, along with their cross-correlations and fluctuation time-scales, when there is a power-law spectrum of density perturbations in a thin ‘equivalent screen’ of scattering material. In this work, we extend the analysis to include refraction-induced fluctuations in intrinsically diffractive quantities such as the scintillation time-scale, t_s, and the decorrelation bandwidth, ν_(dc). We then use the theory to study the drifting bands in dynamic scintillation spectra caused by the dispersive steering of the diffraction pattern. We also estimate the fluctuations in the position of the image on the sky, rates of variation of intensity and position, and the root mean square elongation of the scatter-broadened image. We make two further extensions of the theory. First we show that, despite certain formal divergences, the theory can be extended to accommodate steeper density fluctuation spectra (power-law indices β > 4) than the conventionally assumed Kolmogorov spectrum (β = 11/3). Secondly, we test the validity of the thin-screen approximation, developing a formalism to treat scattering in an extended medium. We find that the thin-screen theory sometimes underestimates the refractive fluctuations by a factor ∼2. The auto- and cross-correlations of the various observables are calculated and comparison is made with the known scintillation properties of pulsars to select those effects most suited to observational verification. The predicted cross-correlation between decorrelation bandwidth and flux fluctuations seems particularly suitable for this purpose. These measurements should, in turn, provide insights into the density fluctuation spectrum and the distribution of the scattering along the line-of-sight

Low-frequency variability of pulsars

Several recent observational and theoretical investigations have suggested that long-wavelength (⁠≲ 10^(14) cm⁠) density fluctuations in the interstellar medium may have a major influence on observations of pulsars and extragalactic radio sources. These long-wavelength fluctuations are responsible for refractive focusing (in contrast to the diffractive scintillation which is conventionally attributed to shorter wavelength fluctuations), and may cause the monthly to annual variations in pulsar flux densities observed at low frequency. Fluctuations in the angular sizes, pulse arrival times and pulse widths of pulsars should also be observable and should be cross-correlated with the flux density variations. The magnitude of these correlations, and their dependence upon the time lag and the observing wavelength, for different power-law spectra of density fluctuations are estimated. It appears that if the flux variability is interstellar in origin, then the spectrum must have a somewhat steeper logarithmic slope that the value (∼11/3) given by the standard ‘Kolmogorov’ spectrum. Sensitive observations on selected pulsars will be able to confirm the importance of refractive effects in the interstellar medium and also determine the slope of the density fluctuation spectrum

Use of nanomaterials in water purification

The recent earthquake in Haiti has focused worldwide attention on the need for improved water purification materials and systems. Numerous individuals, religious charities, non-governmental organizations, and private companies have sent water purifications systems to Haiti in recent months in order to stem the spread of waterborne diseases. This recent tragedy has placed a spotlight on the ongoing problem of inadequate access to safe water in developing countries. The United Nations estimates that 1.1 billion people, or eighteen per cent of the world population, cannot obtain safe water at this time. In developing countries, waterborne diseases such as cholera, dysentery, enteric fever, and hepatitis A are quite common. Endemic diarrheal diseases place individuals, particularly children, at risk of arrested growth, malnutrition, and neurological conditions. The World Health Organization states that 1.6 million individuals, mostly young children, die from diarrheal diseases each year

Open innovation using satellite imagery for initial site assessment of solar photovoltaic projects

One of the responses to the fight against climate change by the developing world has been the large-scale adoption of solar energy. The adoption of solar energy in countries like India is propagating mainly through the development of energy producing photovoltaic farms. The realization of solar energy producing sites involves complex decisions and processes in the selection of sites whose knowhow may not rest with all the stakeholders supporting (e.g., banks financing the project) the industry value chain. In this article, we use the region of Bangalore in India as the case study to present how open innovation using satellite imagery can provide the necessary granularity to specifically aid in an independent initial assessment of the solar photovoltaic sites. We utilize the established analytical hierarchy process over the information extracted from open satellite data to calculate an overall site suitability index. The index takes into account the topographical, climatic, and environmental factors. Our results explain how the intervention of satellite imagery-based big data analytics can help in buying the confidence of investors in the solar industry value chain. Our study also demonstrates that open innovation using satellites can act as a platform for social product development

A Bayesian regularization-backpropagation neural network model for peeling computations

Bayesian regularization-backpropagation neural network (BR-BPNN) model is employed to predict some aspects of the gecko spatula peeling viz. the variation of the maximum normal and tangential pull-off forces and the resultant force angle at detachment with the peeling angle. K-fold cross validation is used to improve the effectiveness of the model. The input data is taken from finite element (FE) peeling results. The neural network is trained with 75% of the FE dataset. The remaining 25% are utilized to predict the peeling behavior. The training performance is evaluated for every change in the number of hidden layer neurons to determine the optimal network structure. The relative error is calculated to draw a clear comparison between predicted and FE results. It is shown that the BR-BPNN model in conjunction with k-fold technique has significant potential to estimate the peeling behavior.Comment: 18 pages, 9 figure

Low-frequency variability of pulsars

Several recent observational and theoretical investigations have suggested that long-wavelength (⁠≲ 10^(14) cm⁠) density fluctuations in the interstellar medium may have a major influence on observations of pulsars and extragalactic radio sources. These long-wavelength fluctuations are responsible for refractive focusing (in contrast to the diffractive scintillation which is conventionally attributed to shorter wavelength fluctuations), and may cause the monthly to annual variations in pulsar flux densities observed at low frequency. Fluctuations in the angular sizes, pulse arrival times and pulse widths of pulsars should also be observable and should be cross-correlated with the flux density variations. The magnitude of these correlations, and their dependence upon the time lag and the observing wavelength, for different power-law spectra of density fluctuations are estimated. It appears that if the flux variability is interstellar in origin, then the spectrum must have a somewhat steeper logarithmic slope that the value (∼11/3) given by the standard ‘Kolmogorov’ spectrum. Sensitive observations on selected pulsars will be able to confirm the importance of refractive effects in the interstellar medium and also determine the slope of the density fluctuation spectrum

Refractive effects in pulsar scintillation

Recent studies have focused attention on the refractive effects of long-wavelength (≲ 10^(14) cm) electron density fluctuations in the interstellar medium upon radio observations of pulsars and compact extragalactic radio sources. In earlier work, a simple scattering model was introduced which allowed us to compute fluctuations in mean intensity, image size, pulse width and pulse arrival time, along with their cross-correlations and fluctuation time-scales, when there is a power-law spectrum of density perturbations in a thin ‘equivalent screen’ of scattering material. In this work, we extend the analysis to include refraction-induced fluctuations in intrinsically diffractive quantities such as the scintillation time-scale, t_s, and the decorrelation bandwidth, ν_(dc). We then use the theory to study the drifting bands in dynamic scintillation spectra caused by the dispersive steering of the diffraction pattern. We also estimate the fluctuations in the position of the image on the sky, rates of variation of intensity and position, and the root mean square elongation of the scatter-broadened image. We make two further extensions of the theory. First we show that, despite certain formal divergences, the theory can be extended to accommodate steeper density fluctuation spectra (power-law indices β > 4) than the conventionally assumed Kolmogorov spectrum (β = 11/3). Secondly, we test the validity of the thin-screen approximation, developing a formalism to treat scattering in an extended medium. We find that the thin-screen theory sometimes underestimates the refractive fluctuations by a factor ∼2. The auto- and cross-correlations of the various observables are calculated and comparison is made with the known scintillation properties of pulsars to select those effects most suited to observational verification. The predicted cross-correlation between decorrelation bandwidth and flux fluctuations seems particularly suitable for this purpose. These measurements should, in turn, provide insights into the density fluctuation spectrum and the distribution of the scattering along the line-of-sight