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Co-processing active pharmaceutical ingredients (APIs) with excipients is a promising particle engineering technique to improve the API physical properties, which can lead to more robust downstream drug product manufacturing and improved drug product attributes. Excipients provide control over critical API attributes like particle size and solid-state outcomes. Eudragit E100 is a widely used polymeric excipient to modulate drug release. Being cationic, it is primarily employed as a precipitation inhibitor to stabilize amorphous solid dispersions. In this work, we demonstrate how co-processing of E100 with naproxen (NPX) (a model hydrophobic API) into monodisperse emulsions via droplet microfluidics followed by solidification via solvent evaporation allows the facile fabrication of compact, monodisperse, and spherical particles with an expanded range of solid-state outcomes spanning from amorphous to crystalline forms. Low E100 concentrations (≤26% w/w) yield crystalline microparticles with a stable NPX polymorph distributed uniformly across the matrix at a high drug loading (∼89% w/w). Structurally, E100 incorporation reduces the size of primary particles comprising the co-processed microparticles in comparison to neat API microparticles made using the same technique and the as-received API powder. This reduction in primary particle size translates into an increased internal porosity of the co-processed microparticles, with specific surface area and pore volume ∼9 times higher than the neat API microparticles. These E100-enabled structural modifications result in faster drug release in acidic media compared to neat API microparticles. Additionally, E100-NPX microparticles have a significantly improved flowability compared to neat API microparticles and as-received API powder. Overall, this study demonstrates a facile microfluidics-based co-processing method that broadly expands the range of solid-state outcomes obtainable with E100 as an excipient, with multiscale control over the key attributes and performance of hydrophobic API-laden microparticles.

Background: Ayushman Bharat Program was announced by Government of India in February 2018 with a vision, which is supposed to deliver comprehensive primary health care services to the entire population. Objectives: To obtain views of FLWs about their changing role at health & wellness centre and the challenges being faced by them in service delivery. Methods: A qualitative study done in 10 Health and wellness centres selected nearby Narayan Medical College & Hospital of Rohtas District of Bihar. The frontline workers posted in the selected HWCs were the study participants. Total duration of the study was 10 months. IDI of FLWs were done and the analysis of the verbatims was done using ATLAS-Ti (Free trial version) software. Results: After analysis of the verbatims two broad themes were made and there were several domains & codes under which the result was stated. It was observed that the frontline workers posted at the selected health & wellness centres were aware of the expanded range of services like yoga, school health, geriatric & palliative care being provided but they were also facing some challenges like manpower, equipment, working hour in service delivery.

This experimental study reports first observations of (i) SOA boundary shift in AlGaN/GaN HEMTs and (ii) early time-to-fail of vertical AlGaN/GaN epi-stack under fast changing (sub-10ns rise time) cyclic pulse transient stress, which otherwise qualified for 600 V DC stress. It is shown that a epi stack qualified for 10 years lifetime under DC stress, fails faster under cyclic transient stress. The drain-to-substrate leakage exhibits different trends under DC and pulse stress. Integrated electrical and mechanical stress characterization routine involving Raman/ PL mapping, PFM and CL spectroscopy along with atomistic simulations reveals material limited unique failure physics under transient stress condition. Failure analysis using cross-sectional SEM and TEM investigations reveal signature of different degradation and failure mechanism under transient and DC stress conditions. A failure model is proposed for rapid breakdown of AlGaN/GaN epi-stack under cyclic transient stress and it is experimentally validated.

Upconversion nanoparticles (UCNPs) have been used effectively as light transducers to convert near-infrared irradiation to short-wavelength emissions for photoactivation in deep tissues. UCNPs with single/multiple emissions under excitation at a single wavelength can be used for simultaneous activation of single or multiple photosensitive molecules only; an ideal multifunctional UCNP nanoplatform should not only have the ability to load multiple molecules but also should activate them at the right time with the right dose when necessary, depending upon the application for which it is used. The control of many biological processes requires complex (simultaneous or subsequent) photoactivation at different time points. Subsequent photoactivation requires UCNPs with orthogonal fluorescence emissions, which can be controlled independently. So far, there are only a few reports about UCNPs with orthogonal emissions. Synthesis of these orthogonal emission nanoparticles is complicated and tedious because nanoparticles with multiple shells need to be synthesized, and different lanthanide ions need to be doped into different shells. Also, there is no flexibility for changing the doped ions and emission profile after the nanoparticles are produced. Here, we have demonstrated a versatile method to modularly assemble individual UCNPs into UCNP clusters (UCNPs-C) with adjustable emissions. The synthesis is much easier, and there is a lot of flexibility in changing the particle size, shape, doped ions, and emission profile. We have demonstrated the use of such UCNPs-C for color encoding at the nanoscale. We further designed orthogonal photoactivatable UCNPs-C (OP-UCNPs-C), which can be independently activated under 980 nm excitation for red emission and 808 nm excitation for UV/blue emission. These OP-UCNPs-C were used for independent activation of processes for cell imaging (980 nm) and drug delivery (808 nm). In comparison to the traditional nonprogrammed activation, a programmed controlled imaging and drug delivery process could guarantee highly targeted and enhanced cell death of cancerous cells.

In this paper, the impact of donor and acceptor states at the Schottky interface of fully recessed AlGaN/GaN Schottky diode is physically modeled using device TCAD and detailed experiments. This allowed us to develop physical insights into recessed AlGaN/GaN diode’s reverse breakdown, reverse leakage, and ON-state performance as a function of interface states and provided design guidelines to engineer fully recessed AlGaN/GaN Schottky diode for the maximum reverse breakdown and least reverse leakage without compromising its ON-state performance. It has been observed that donor states are responsible for high reverse leakage and reduced breakdown performance in Schottky diodes. On the other hand, the presence of acceptor states at the interface improves the diode leakage and breakdown voltage. Experiments involve a number of dry and wet surface treatments to: 1) validate computational findings and 2) find ways to cure or passivate donor states affected Schottky interface/recessed region. The introduction of acceptor traps at the Schottky interface has been proposed and experimentally verified using the Fluorine implant to cure donor state-affected Schottky interface, which improves the breakdown and reverse leakage characteristics significantly.

Rare earth ions doped upconversion nanoparticles (UCNPs) are capable of stepwisely converting two or more lower energy near-infrared (NIR) excitation photons into a higher energy visible and ultraviolet emission photon, resulting in a large anti-Stokes shift of several hundred nanometers. Because the f-electron configurations of lanthanide ions have abundant energy levels, and many of them possess long lifetimes, UCNPs exhibit unique optical properties including optical tunability over emission wavelengths and lifetimes, better photo-stability and improved monochromatic color-purity and spatial resolution. However, the low luminescent efficiency, largely owing to their substantially weak and narrow band absorptions, has greatly hampered the translation of UCNPs-based technologies from the academic stage to real world products. Recently, increasing efforts have been paid on boosting the upconversion luminescence brightness and efficiency, including inert shells coating, high concentration of activators dop...

Quenching of lanthanide-doped upconversion nanoparticle (UCNP) luminescence at high dopant concentrations is an existing challenge that hampers their desired applications. It has already been reported that concentration quenching is strongly coupled to surface quenching. However, in this study we found that surface quenching is not the only cause for concentration quenching and concentration quenching was still observed in UCNPs with a well-protected surface. By using a mathematical model to better understand the processes, we proposed that this concentration quenching could be minimized by moving the extra sensitizers (Yb3+) to a different layer. To achieve this, a new tri-layer UCNP structure with sensitizers isolated in the middle layer was developed. It was observed that the quenching was reduced, and the luminescence intensity was enhanced up to 11.8 times in comparison with the brightest UCNPs without the sensitizing layer.

Lanthanide-doped upconversion nanoparticles (UCNPs) are of great interest for biomedical applications. Currently, the applicability of UCNP bionanotechnology is hampered by the generally low luminescence intensity of UCNPs and inefficient energy transfer from UCNPs to surface-bound chromophores used e.g. for photodynamic therapy or analyte sensing. In this work, we address the low-efficiency issue by developing versatile core–shell nanostructures, where high-concentration sensitizers and activators are confined in the core and shell region of representative hexagonal NaYF4:Yb,Er UCNPs. After doping concentration optimization, the sensitizer-rich core is able to harvest/accumulate more excitation energy and generate almost one order of magnitude higher luminescence intensity than conventional homogeneously doped nanostructures. At the same time, the activator ions located in the shell enable a ∼6 times more efficient resonant energy transfer from UCNPs to surface-bound acceptor dye molecules due to the short distance between donor–acceptor pairs. Our work provides new insights into the rational design of UCNPs and will greatly increase the general applicability of upconversion nanotechnologies.

Background: Antenatal check- up is the routine health care of presumed healthy pregnant women without symptoms (screening), in order to diagnose diseases or complicating obstetric conditions without symptoms, and to provide information about lifestyle, pregnancy and delivery. Early registration to antenatal care is imperative for the timely diagnosis and treatment of pregnancy related morbidities. Objectives: This study aims to find the association between socio demographic factors and number of ANC visits of patients attending the Department of Obstetrics and Gynaecology, RIMS, Ranchi. Methods: This was a cross sectional hospital based study done in Obs. & Gynae. Department of RIMS, Ranchi for a duration of 3 months. All pregnant women admitted on the beds with odd numbers in ward during the data collection period were included. Total sample size during this period came out to be 160. Templates were generated in MS excel sheet and data analysis was done using SPSS software (version20.0). Results: On analysis and applying chi-square statistics test it was found that half of the respondents had their first ANC visit within 12 weeks of pregnancy. Various socio-demographic factors like husband education, residence and occupation were significantly associated (p

Encoded nano-structures/particles have been used for barcoding and are in great demand for the simultaneous analysis of multiple targets. Due to their nanoscale dimension(s), nano-barcodes have been implemented favourably for bioimaging, in addition to their security and multiplex bioassay application. In designing nano-barcodes for a specific application, encoding techniques, synthesis strategies, and decoding techniques need to be considered. The encoding techniques to generate unique multiple codes for nano-barcodes are based on certain encoding elements including optical (fluorescent and non-fluorescent), graphical, magnetic, and phase change properties of nanoparticles or their different shapes and sizes. These encoding elements can generally be embedded inside, decorated on the surface of nanostructures or self-assembled to prepare the nano-barcodes. The decoding techniques for each encoding technique are different and need to be suitable for the desired applications. This review will provide a thorough discussion on designing nano-barcodes, focusing on the encoding techniques, synthesis methods, and decoding for applications including bio-detection, imaging, and anti-counterfeiting. Additionally, associated challenges in the field and potential solutions will also be discussed. We believe that a comprehensive understanding on this topic could significantly contribute towards the advancement of nano-barcodes for a broad spectrum of applications.

The goal of cancer immunotherapy is the selective killing of malignant cells by the cooperated efforts of immune cells at the primary and secondary sites. Here, we developed folic acid and secondary lymphoid tissue chemokine-loaded mesoporous silica-modified upconversion nanoparticle construct as a targeting, delivery, and imaging system to attract immune cells to folate receptor-expressing tumor cells. The effectiveness of the nanoparticles in targeting dendritic cells and T cells to the tumor compartment was tested in a vasculature-tumor interface model constructed from the co-culture of endothelial cells and ovarian cancer cells, in different interconnected channels in a microfluidic device. In comparison to the unconjugated nanoparticles, the folic acid-conjugated nanoparticles efficiently diffuse across the engineered blood vessel and specifically target the folate receptor-expressing ovarian cancer cells. The developed microfluidic platform was further used to demonstrate increased dendritic cell and T cell migration toward the ovarian cancer cell channel induced by the presence of the chemokine- and folic acid-loaded nanoparticles. The nanoparticle construct did not exhibit any significant cyto- and hemotoxicity. This proof of concept showed the potential of the nanoparticles to target cancer cells as well as to recruit dendritic cells and T cells to tumor sites to augment the weak host immune response.

Microbead-based point-of-care testing (POCT) has demonstrated great promise in translating detection modalities from bench-side to bed-side. This is due to the ease of visualization, high surface area-to-volume ratio of beads for efficient target binding, and efficient encoding capability for simultaneous detection of multiple analytes. This review (with 112 references) summarizes the progress made in the field of fluorescent microbead-based POCT. Following an introduction into the field, a first large section sums up techniques and materials for preparing microbeads, typically of dye-labelled particles, various kinds of quantum dots and upconversion materials. Further subsections cover the encapsulation of nanoparticles into microbeads, decoration of nanoparticles on microbeads, and in situ embedding of nanoparticles during microbead synthesis. A next large section summarizes microbead-based fluorometric POCT, with subsections on detection of nucleic acids, proteins, circulating tumor cells and bacteria. A further section covers emerging POCT based on the use of smartphones or flexible microchips. The last section gives conclusions and an outlook on current challenges and possible solutions. Aside from giving an overview on the state of the art, we expect this article to boost the further development of POCT technology. Graphical Abstract Schematic presentation of the fabrication of microbeads, the detection targets of interest including bacteria, circulating tumor cells (CTCs), protein and nucleic acid, and the emerging point-of-care testing (POCT) platform. The colored wheels of the bus represent the fluorescent materials embedded in (red color) or decorated on the surface of microbeads (green color).

This work demonstrates UV assisted probing of deep level traps in dielectric/GaN interface. The deep level donor traps lead to threshold voltage and gate leakage instabilities in GaN MISHEMTs. While UV exposure excites the deep traps, gate bias can sweep the trap energy state and trigger de-trapping. The recovery transient is evaluated to study the trap time constant. Besides, this work reveals a non-destructive technique to probe intrinsic traps as the UV exposure does not change the trap density across the device.

Upconversion nanoparticles (UCNPs) are the preferred choice for deep-tissue photoactivation, owing to their unique capability of converting deep tissue-penetrating near-infrared light to UV/visible light for photoactivation. Programmed photoactivation of multiple molecules is critical for controlling many biological processes. However, syntheses of such UCNPs require epitaxial growth of multiple shells on the core nanocrystals and are highly complex/time-consuming. To overcome this bottleneck, we have modularly assembled two distinct UCNPs which can individually be excited by 980/808 nm light, but not both. These orthogonal photoactivable UCNPs superballs are used for programmed photoactivation of multiple therapeutic processes for enhanced efficacy. These include sequential activation of endosomal escape through photochemical-internalization for enhanced cellular uptake, followed by photocontrolled gene knockdown of superoxide dismutase-1 to increase sensitivity to reactive oxygen species and finally, photodynamic therapy under these favorable conditions. Such programmed activation translated to significantly higher therapeutic efficacy in vitro and in vivo in comparison to conventional, non-programmed activation., The synthesis of nanoparticles capable of orthogonal photo-activity is complex. Here, the authors report on an assembly process of two distinct nanoparticles into composite nanoparticles as a simple method and report on the application in photodynamic therapy and siRNA delivery in tumour therapy.

The authors describe the use of white-light emitting upconversion nanoparticles (WL-UCNPs) for visual detection of the pesticide thiram. The method is demonstrated to undergo a better discernable color change upon target binding. The WL-UCNPs are modified with the lead(II)-dithizone complex which acts as the energy acceptor and recognition unit. This leads to quenching of the blue (475 nm) and green (545 nm) emissions of the WL-UCNPs, while the red emission (650 nm) remains unaffected. Upon addition of thiram, the quenched emissions are recovered, with a linear signal increase in the range from 2 nM to 20 nM of thiram and a limit of detection of 0.26 nM. The nanoprobe was further integrated into a test paper for visual detection. The concentration-dependent color change that varies from red to cyan and bluish violet and then to white can be visually distinguished. Graphical abstract Schematic presentation of a white-light emissive upconversion nanoparticle based test paper for color-discernable detection of the pesticide thiram. The test stripe exhibits a concentration-dependent color variation spanning from red, cyan, to bluish violet, and at last to white.

Optogenetics is widely used to interrogate the neural circuits underlying disease and has most recently been harnessed for therapeutic applications. The optogenetic toolkit consists of light-responsive proteins that modulate specific cellular functions, vectors for the delivery of the transgenes that encode the light-responsive proteins to targeted cellular populations, and devices for the delivery of light of suitable wavelengths at effective fluence rates. A refined toolkit with a focus towards translational uses would include efficient and safer viral and non-viral gene-delivery vectors, increasingly red-shifted photoresponsive proteins, nanomaterials that efficiently transduce near-infrared light deep into tissue, and wireless implantable light-delivery devices that allow for spatiotemporally precise interventions at clinically relevant tissue depths. In this Review, we examine the current optogenetics toolkit and the most notable preclinical and translational uses of optogenetics, and discuss future methodological and translational developments and bottlenecks.

This experimental study reports first observations of (i) SOA boundary shift in GaN HEMTs and (ii) early time to fail of vertical AIGaN/GaN Epi stack under fast changing (sub-10ns risetime) cyclic transient stress conditions for a 600V qualified commercial grade HEMT stack. It is shown that a stack qualified for 10 years lifetime under DC stress, fails faster under cyclic transient stress. Integrated electrical and mechanical stress characterization routine involving Raman/PL mapping and CL spectroscopy reveals material limited unique failure physics under transient stress condition. Failure analysis using cross-sectional TEM investigations reveal signature of different degradation and failure mechanism under transient and DC stress conditions. A failure model is proposed for failure under cyclic transient stress.

Fluorescently encoded microbeads are in demand for multiplexed applications in different fields. Compared to organic dye-based commercially available Luminex’s xMAP technology, upconversion nanoparticles (UCNPs) are better alternatives due to their large anti-Stokes shift, photostability, nil background, and single wavelength excitation. Here, we developed a new multiplexed detection system using UCNPs for encoding poly(ethylene glycol) diacrylate (PEGDA) microbeads as well as for labeling reporter antibody. However, to prepare UCNPs-encoded microbeads, currently used swelling-based encapsulation leads to non-uniformity, which is undesirable for fluorescence-based multiplexing. Hence, we utilized droplet microfluidics to obtain encoded microbeads of uniform size, shape, and UCNPs distribution inside. Additionally, PEGDA microbeads lack functionality for probe antibodies conjugation on their surface. Methods to functionalize the surface of PEGDA microbeads (acrylic acid incorporation, polydopamine coating) reported thus far quench the fluorescence of UCNPs. Here, PEGDA microbeads surface was coated with silica followed by carboxyl modification without compromising the fluorescence intensity of UCNPs. In this study, droplet microfluidics-assisted UCNPs-encoded microbeads of uniform shape, size, and fluorescence were prepared. Multiple color codes were generated by mixing UCNPs emitting red and green colors at different ratios prior to encapsulation. UCNPs emitting blue color were used to label the reporter antibody. Probe antibodies were covalently immobilized on red UCNPs-encoded microbeads for specific capture of human serum albumin (HSA) as a model protein. The system was also demonstrated for multiplexed detection of both human C-reactive protein (hCRP) and HSA protein by immobilizing anti-hCRP antibodies on green UCNPs. Electronic supplementary material The online version of this article (10.1007/s40820-017-0184-y) contains supplementary material, which is available to authorized users.

Background: Mother and child protection card (MCP card) is a common card to maintain the record of health care delivery including antenatal care, post-natal care and care of the child that can be used by both the health personnel and the beneficiaries. This study was done among Sahiyyas and AWWs to assess their awareness about MCP card, to find out their training status, to assess their knowledge and skill in recording information in MCP card and assess their role perception of MCP card.Methods: A multi-stage stratified random sampling method was adopted to select Sahiyyas and AWW’s for interview between November 2017 – April 2018 (6 months). 17 Sahiyya and 19 AWWs were interviewed using a pre tested schedule. Templates were generated in MS Excel sheet and data analysis was done using SPSS software (version 20).Results: All the Anganwadi workers who were included in this study were aware about the MCP card whereas 15 out of 17 sahiyyas had awareness about the existence of MCP card. Training in order to orient the AWW and Sahiyya about using MCP card was very low, only 6 out of 19 (31.6%) of AWW had received training and 8 out of 17 (47.1%) Sahiyya’s were trained. We found that majority of the workers and Sahiyya had knowlwdge about most of the sections and had used it to record information in MCP card.Conclusions: Sahiyya’s and AWWs were aware about existence of MCP card, and most of them use it, despite very low training status.

The Honshu, Japan earthquake of 11th March 2011, caused severe hazard in Japan and neighboring countries. It revealed the need and importance of warning system for Tsunami generation to minimize the casualties. Seismograms of the Honshu earthquake event (recorded by broadband seismograms, being operated in the NW Himalaya by Wadia Institute of Himalayan Geology, Dehradun) are used for quick prediction of tsunami. The frequency content of these seismograms is studied and energy content in high frequencies is calculated, which is used to give tsunami warning. It is observed that wavelet coefficients for frequencies greater than 0.33 Hz tsunamigenic earthquakes do not show significant energy in the spectrum. However, significant energy is found in wavelet spectrum of non-tsunamigenic earthquake. In this paper we present the wavelet analysis on the Honshu, Japan earthquake of 11th March, 2011. Some other global tsunamigenic and non-tsunamigenic events are also analyzed for test and comparison purpose of the methodology used.